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Clinical Trial Results:
A 52-week, phase 3, multicentre, randomised, double blind, efficacy and safety study, comparing GSK3196165 with placebo and with tofacitinib in combination with conventional synthetic DMARDs, in participants with moderately to severely active rheumatoid arthritis who have an inadequate response to conventional synthetic DMARDs or biologic DMARDs.

Summary
EudraCT number	2019-000867-26
Trial protocol	GB DE ES PL BG EE HU
Global end of trial date	18 Jan 2023

Results information
Results version number	v2(current)
This version publication date	01 Dec 2023
First version publication date	08 Oct 2023
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

201791

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

GreatWest Road, Brentford,Middlesex, United Kingdom, TW8 9GS

Public contact

GlaxoSmithKline, GSK Response Center, +1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GlaxoSmithKline, GSK Response Center, +1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

09 Mar 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Jan 2023

Was the trial ended prematurely?

Main objective of the trial

To compare the efficacy of GSK3196165 at doses of 90 mg and 150 mg weekly versus placebo for the treatment of participants with moderately to severely active RA who are on a stable background of csDMARDs and who have had an inadequate response to csDMARDs or bDMARDs.

Protection of trial subjects

Not Applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Jun 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 187

Country: Number of subjects enrolled

Australia: 6

Country: Number of subjects enrolled

Bulgaria: 80

Country: Number of subjects enrolled

China: 165

Country: Number of subjects enrolled

Colombia: 45

Country: Number of subjects enrolled

Estonia: 48

Country: Number of subjects enrolled

France: 2

Country: Number of subjects enrolled

Germany: 22

Country: Number of subjects enrolled

Hungary: 28

Country: Number of subjects enrolled

Japan: 224

Country: Number of subjects enrolled

Mexico: 124

Country: Number of subjects enrolled

Poland: 467

Country: Number of subjects enrolled

Russian Federation: 141

Country: Number of subjects enrolled

Korea, Democratic People's Republic of: 27

Country: Number of subjects enrolled

Spain: 11

Country: Number of subjects enrolled

Thailand: 9

Country: Number of subjects enrolled

United Kingdom: 11

Country: Number of subjects enrolled

United States: 167

Worldwide total number of subjects

1764

EEA total number of subjects

658

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

1375

From 65 to 84 years

388

85 years and over

Subject disposition

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Recruitment details

For Global and Asia cohorts, participants were randomized in ratio of 6:6:3:1:1:1 to 3 experimental and 3 Placebo arms. At Week 12, participants from one of the three placebo arms switched to experimental arms, receiving intervention for 40 weeks. Participants who were randomized to experimental arms from day 1, received intervention for 52 weeks.

Screening details

Total of 1764 participants were enrolled(1625 in Global and 139 in Asia cohorts which is supplementary to Global Cohort). One participant from GSK3196165 150mg (Asia cohort) arm was randomized but not treated. Study was terminated early only for Asia Cohort as limited efficacy did not support benefit risk profile of Otilimab as potential treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Yes

GSK3196165 90mg + csDMARD (Global Cohort)

Arm description

Participants in Global Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARD).

Arm type

Experimental

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

GSK3196165 150mg + csDMARD (Global Cohort)

Arm description

Participants in Global Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Arm type

Experimental

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Tofacitinib 5mg + csDMARD (Global Cohort)

Arm description

Participants in Global Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Arm type

Active comparator

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)

Arm description

Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

Arm type

Placebo

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD from week 12 to week 52.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)

Arm description

Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

Arm type

Placebo

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD from week 12 to week 52.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)

Arm description

Participants in Global Cohort received Placebo capsule BID in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo capsule to Tofacitinib 5mg, capsule, orally, BID in combination with csDMARD plus placebo injection to maintain the blind for 52 weeks.

Arm type

Placebo

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received Tofacitinib 5mg, capsule, orally, BID in combination with csDMARD plus placebo injection to maintain the blind from week 12 to week 52 weeks.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

GSK3196165 90mg + csDMARD (Asia Cohort)

Arm description

Participants in Asia Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Arm type

Experimental

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

GSK3196165 150mg + csDMARD (Asia Cohort)

Arm description

Participants in Asia Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Arm type

Experimental

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Tofacitinib 5mg + csDMARD (Asia Cohort)

Arm description

Participants in Asia Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Arm type

Active comparator

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)

Arm description

Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

Arm type

Placebo

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD from week 12 to week 52.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)

Arm description

Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

Arm type

Placebo

Investigational medicinal product name

GSK3196165

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD from week 12 to week 52.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)

Arm description

Participants in Asia Cohort received Placebo capsule BID in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo capsule to Tofacitinib 5mg, capsule, orally, BID in combination with csDMARD plus placebo injection to maintain the blind for 52 weeks.

Arm type

Placebo

Investigational medicinal product name

Tofacitinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received Tofacitinib 5mg, capsule, orally, BID in combination with csDMARD plus placebo injection to maintain the blind from week 12 to week 52 weeks.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

Number of subjects in period 1 ^[1]	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Started	545	539	271	91	89	90	47	49	19	6	8	9
Completed	461	447	231	73	69	68	25	23	15	4	5	4
Not completed	84	92	40	18	20	22	22	26	4	2	3	5
Physician decision	5	8	4	1	5	2	4	5	-	1	-	-
Consent withdrawn by subject	32	35	12	8	6	8	2	3	-	-	-	1
Adverse event, non-fatal	23	20	16	6	4	5	1	5	-	-	1	1
STUDY TERMINATED BY SPONSOR	-	-	-	-	-	-	8	11	2	1	2	3
PROTOCOL-SPECIFIED WITHDRAWAL CRITERION MET	3	12	2	-	2	1	1	1	1	-	-	-
Lost to follow-up	6	5	5	1	-	2	-	-	-	-	-	-
Lack of efficacy	14	12	1	2	3	4	6	1	1	-	-	-
Protocol deviation	1	-	-	-	-	-	-	-	-	-	-	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Total of 1764 participants were enrolled in the study (1625 in Global and 139 in Asia cohorts which is supplementary to Global Cohort). One participant from GSK3196165 150mg (Asia cohort) arm was randomized but not treated. The study was terminated early only for Asia Cohort as the limited efficacy did not support the benefit risk profile of Otilimab as a potential treatment.

Baseline characteristics

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Reporting group title

GSK3196165 90mg + csDMARD (Global Cohort)

Reporting group description

Reporting group title

GSK3196165 150mg + csDMARD (Global Cohort)

Reporting group description

Participants in Global Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Reporting group title

Tofacitinib 5mg + csDMARD (Global Cohort)

Reporting group description

Participants in Global Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Reporting group title

Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)

Reporting group description

Reporting group title

Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)

Reporting group description

Reporting group title

Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)

Reporting group description

Reporting group title

GSK3196165 90mg + csDMARD (Asia Cohort)

Reporting group description

Participants in Asia Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Reporting group title

GSK3196165 150mg + csDMARD (Asia Cohort)

Reporting group description

Participants in Asia Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Reporting group title

Tofacitinib 5mg + csDMARD (Asia Cohort)

Reporting group description

Participants in Asia Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Reporting group title

Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)

Reporting group description

Reporting group title

Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)

Reporting group description

Reporting group title

Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)

Reporting group description

Reporting group values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)	Total
Number of subjects	545	539	271	91	89	90	47	49	19	6	8	9	1763
Age Categorical
Units: Participants
18-49 Years	172	150	79	30	23	23	19	21	3	2	3	3	528
50-64 Years	254	264	125	47	43	45	23	22	11	3	5	5	847
>=65 Years	119	125	67	14	23	22	5	6	5	1	0	1	388
Sex: Female, Male
Units: Participants
Female	431	430	229	68	73	73	34	37	12	4	5	7	1403
Male	114	109	42	23	16	17	13	12	7	2	3	2	360
Race/Ethnicity, Customized
Units: Subjects
AMERICAN INDIAN OR ALASKA NATIVE	29	39	21	6	4	6	0	0	0	0	0	0	105
ASIAN	96	98	49	16	16	16	47	49	19	6	8	9	429
BLACK OR AFRICAN AMERICAN	10	8	3	2	0	1	0	0	0	0	0	0	24
WHITE	409	393	197	67	69	67	0	0	0	0	0	0	1202
MULTIPLE	1	0	0	0	0	0	0	0	0	0	0	0	1
MISSING	0	1	1	0	0	0	0	0	0	0	0	0	2

End points

Top of page

Reporting group title

GSK3196165 90mg + csDMARD (Global Cohort)

Reporting group description

Reporting group title

GSK3196165 150mg + csDMARD (Global Cohort)

Reporting group description

Participants in Global Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Reporting group title

Tofacitinib 5mg + csDMARD (Global Cohort)

Reporting group description

Participants in Global Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Reporting group title

Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)

Reporting group description

Reporting group title

Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)

Reporting group description

Reporting group title

Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)

Reporting group description

Reporting group title

GSK3196165 90mg + csDMARD (Asia Cohort)

Reporting group description

Participants in Asia Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Reporting group title

GSK3196165 150mg + csDMARD (Asia Cohort)

Reporting group description

Participants in Asia Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Reporting group title

Tofacitinib 5mg + csDMARD (Asia Cohort)

Reporting group description

Participants in Asia Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Reporting group title

Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)

Reporting group description

Reporting group title

Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)

Reporting group description

Reporting group title

Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)

Reporting group description

Subject analysis set title

Pooled Placebo (Global Cohort)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12. The placebo arms are pooled into a single placebo arm.

Subject analysis set title

Pooled Placebo (Asia Cohort)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD until Week 12. The placebo arms are pooled into a single placebo arm.

Subject analysis set title

Tofacitinib 5mg + csDMARD (Global Cohort)

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Subject analysis set title

Pooled Placebo (Global Cohort)

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12. The placebo arms are pooled into a single placebo arm.

Primary: Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 superiority comparison with placebo (Global Cohort)

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End point title

Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 superiority comparison with placebo (Global Cohort) ^[1]

End point description

ACR20 is calculated as 20% improvement from Baseline in Tender Joint Count 68 (TJC68), Swollen Joint Count 66 (SJC66) and 20% improvement in 3 of the following 5 measures:Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale [VAS] with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0=least difficulty to 3=extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as reference for the comparison of active treatment arms. The analysis was performed on Intent-to-Treat (ITT) set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Primary

End point timeframe

Week 12

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)	54.9	54.5	71.1	32.5

Statistical Analysis 1

Statistical analysis description

The null hypothesis is defined as there is no difference between the 90mg dose of GSK3196165 and placebo in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 90mg dose of GSK3196165 differs from placebo in the proportion of participants achieving ACR20 response at Week 12.

Comparison groups

GSK3196165 90mg + csDMARD (Global Cohort) v Pooled Placebo (Global Cohort)

Number of subjects included in analysis

815

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.57

Confidence interval

level

95%

sides

2-sided

lower limit

1.87

upper limit

3.53

Statistical Analysis 2

Statistical analysis description

The null hypothesis is defined as there is no difference between the 150mg dose of GSK3196165 and placebo in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 150mg dose of GSK3196165 differs from placebo in the proportion of participants achieving ACR20 response at Week 12.

Comparison groups

GSK3196165 150mg + csDMARD (Global Cohort) v Pooled Placebo (Global Cohort)

Number of subjects included in analysis

809

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.55

Confidence interval

level

95%

sides

2-sided

lower limit

1.85

upper limit

3.5

Statistical Analysis 4

Statistical analysis description

The null hypothesis is defined as there is no difference between the 90 mg dose of GSK3196165 and 05mg dose of Tofacitinib in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 90 mg dose of GSK3196165 differs from 05mg dose of Tofacitinib in the proportion of participants achieving ACR20 response at Week 12.

Comparison groups

GSK3196165 90mg + csDMARD (Global Cohort) v Tofacitinib 5mg + csDMARD (Global Cohort)

Number of subjects included in analysis

816

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

0.66

Statistical Analysis 5

Statistical analysis description

The null hypothesis is defined as there is no difference between the 150mg dose of GSK3196165 and 05mg dose of Tofacitinib in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 150mg dose of GSK3196165 differs from 05mg dose of Tofacitinib in the proportion of participants achieving ACR20 response at Week 12.

Comparison groups

GSK3196165 150mg + csDMARD (Global Cohort) v Tofacitinib 5mg + csDMARD (Global Cohort)

Number of subjects included in analysis

810

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

0.47

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

0.66

Statistical Analysis 3

Statistical analysis description

The null hypothesis is defined as there is no difference between the 05mg dose of Tofacitinib and placebo in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 05mg dose of Tofacitinib differs from placebo in the proportion of participants achieving ACR20 response at Week 12.

Comparison groups

Tofacitinib 5mg + csDMARD (Global Cohort) v Pooled Placebo (Global Cohort)

Number of subjects included in analysis

541

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

5.38

Confidence interval

level

95%

sides

2-sided

lower limit

3.66

upper limit

7.9

Primary: Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 (Asia Cohort)

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End point title

Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 (Asia Cohort) ^[2] ^[3]

End point description

ACR20 is calculated as 20% improvement from Baseline in Tender Joint Count 68 (TJC68), Swollen Joint Count 66 (SJC66) and 20% improvement in 3 of the following 5 measures:Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale [VAS] with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0=least difficulty to 3=extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as reference for the comparison of active treatment arms. The analysis was performed on ITT -Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Primary

End point timeframe

Week 12

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The endpoints are different for the different parts of the study.
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	44	42	19	21
Units: Percentage of participants
number (not applicable)	45.0	40.0	68.0	14.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving Clinical disease activity index (CDAI) total score less than or equal to (<=)10 [CDAI Low disease activity (LDA)] at Week 12 (Global Cohort)

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End point title

Percentage of participants achieving Clinical disease activity index (CDAI) total score less than or equal to (<=)10 [CDAI Low disease activity (LDA)] at Week 12 (Global Cohort) ^[4]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale [VAS] with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. For the purpose of all analyses up to week 12, the placebo arms were pooled into single placebo arm to primarily serve as reference for the comparison of active treatment arms. Analysis was performed on ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 12

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)	26.5	25.1	36.8	11.4

No statistical analyses for this end point

Secondary: Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Global Cohort)

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End point title

Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Global Cohort) ^[5]

End point description

Health Assessment Questionnaire-Disability Index (HAQ-DI) is 20-question instrument that assesses degree of difficulty in accomplishing tasks in eight functional areas:dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score is sum of domain scores divided by number of domains answered. The score ranges from 0 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline. For the purpose of all analyses up to week 12, placebo arms were pooled into single placebo arm to primarily serve as reference for comparison of active treatment arms. The analysis was performed on ITT set using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Scores on a scale
least squares mean (standard error)	-0.32 ± 0.029	-0.31 ± 0.029	-0.46 ± 0.037	-0.14 ± 0.038

No statistical analyses for this end point

Secondary: Percentage of participants achieving 20% improvement in ACR20 at Week 24: non-inferiority comparison with tofacitinib (Global Cohort)

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End point title

Percentage of participants achieving 20% improvement in ACR20 at Week 24: non-inferiority comparison with tofacitinib (Global Cohort) ^[6]

End point description

ACR20 is calculated as a 20% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) [visual analogue scale (VAS) with values from 0=best to 100=worst], Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)]. The analysis was performed on the ITT set using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)	65.0	62.5	79.8

Statistical Analysis 2

Comparison groups

GSK3196165 150mg + csDMARD (Global Cohort) v Tofacitinib 5mg + csDMARD (Global Cohort)

Number of subjects included in analysis

810

Analysis specification

Pre-specified

Analysis type

^[7]

Method

Regression, Logistic

Parameter type

Difference in Percentage

Point estimate

-17.2

Confidence interval

level

95%

sides

2-sided

lower limit

-23.9

upper limit

-10.6

Notes
[7] - Non-inferiority over tofacitinib on ACR20 was concluded if the lower limit of the multiplicity corrected 95% Confidence Interval (CI) in the difference in proportions (GSK3196165 minus tofacitinib) was greater than -12%

Statistical Analysis 1

Comparison groups

GSK3196165 90mg + csDMARD (Global Cohort) v Tofacitinib 5mg + csDMARD (Global Cohort)

Number of subjects included in analysis

816

Analysis specification

Pre-specified

Analysis type

^[8]

Method

Regression, Logistic

Parameter type

Difference in Percentage

Point estimate

-14.7

Confidence interval

level

95%

sides

2-sided

lower limit

-21.3

upper limit

-8.1

Notes
[8] - Non-inferiority over tofacitinib on ACR20 was concluded if the lower limit of the multiplicity corrected 95% Confidence Interval (CI) in the difference in proportions (GSK3196165 minus tofacitinib) was greater than -12%

Secondary: Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[9]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)
Week 24	32.8	34.3	49.6
Week 52	38.3	38.0	56.8

No statistical analyses for this end point

Secondary: Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[10]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Percentage of participants
number (not applicable)
Week 24	37.5	15.9	46.4
Week 52	40.2	38.2	41.3

No statistical analyses for this end point

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 (Global Cohort)

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End point title

Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 (Global Cohort) ^[11]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 12

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)	4.7	4.5	9.7	3.8

No statistical analyses for this end point

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[12]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)
Week 24	6.9	7.2	17.9
Week 52	11.9	10.8	21.2

No statistical analyses for this end point

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[13]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Percentage of participants
number (not applicable)
Week 24	6.6	5.7	11.0
Week 52	11.4	5.6	17.2

No statistical analyses for this end point

Secondary: Percentage of participants achieving 50%/70% improvement in American College of Rheumatology Criteria(ACR50/70) at Week 12 (Global Cohort)

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End point title

Percentage of participants achieving 50%/70% improvement in American College of Rheumatology Criteria(ACR50/70) at Week 12 (Global Cohort) ^[14]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 12

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)
ACR50	21.6	25.1	39.4	9.5
ACR70	6.9	9.6	18.9	4.2

No statistical analyses for this end point

Secondary: Percentage of participants achieving ACR50/70 at Week 24 and ACR20/50/70 Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Percentage of participants achieving ACR50/70 at Week 24 and ACR20/50/70 Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[15]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)
ACR20, Week 52	64.3	65.3	75.6
ACR50, Week 24	31.6	32.8	53.6
ACR50, Week 52	36.5	36.9	52.9
ACR70, Week 24	14.0	13.0	28.7
ACR70, Week 52	19.1	17.5	35.7

No statistical analyses for this end point

Secondary: Percentage of participants achieving ACR50/70 at Week 24 and ACR20/50/70 Week 52 for placebo switched arms (Global Cohort)

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End point title

Percentage of participants achieving ACR50/70 at Week 24 and ACR20/50/70 Week 52 for placebo switched arms (Global Cohort) ^[16]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Percentage of participants
number (not applicable)
ACR20, Week 52	56.3	63.4	70.1
ACR50, Week 24	35.6	27.6	41.8
ACR50, Week 52	43.7	38.5	47.2
ACR70, Week 24	18.7	10.5	21.8
ACR70, Week 52	22.6	15.4	20.7

No statistical analyses for this end point

Secondary: Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 (Global Cohort)

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End point title

Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 (Global Cohort) ^[17]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 12

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)	23.2	23.6	40.7	10.4

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 (Global Cohort)

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End point title

Percentage of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 (Global Cohort) ^[18]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 12

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)	13.2	14.6	23.6	7.3

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[19]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)
Week 24	31.3	33.0	55.3
Week 52	35.4	36.4	53.9

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[20]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)
Week 24	19.9	24.1	37.1
Week 52	26.2	22.9	38.8

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[21]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Percentage of participants
number (not applicable)
Week 24	37.5	19.3	42.7
Week 52	41.4	31.4	39.6

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[22]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Percentage of participants
number (not applicable)
Week 24	30.2	14.2	23.4
Week 52	28.0	16.6	31.5

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 (Global Cohort)

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End point title

Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 (Global Cohort) ^[23]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 12

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)	11.5	12.0	23.2	5.5

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[24]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)
Week 24	16.7	19.6	38.0
Week 52	23.6	21.2	41.2

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 (Global Cohort)

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End point title

Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 (Global Cohort) ^[25]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 12

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)	7.1	6.1	12.6	3.8

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[26]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)
Week 24	8.7	11.7	23.4
Week 52	14.3	11.7	19.9

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[27]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Percentage of participants
number (not applicable)
Week 24	23.3	11.5	23.8
Week 52	30.4	19.8	26.4

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[28]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Percentage of participants
number (not applicable)
Week 24	13.4	6.2	13.4
Week 52	16.1	11.5	13.4

No statistical analyses for this end point

Secondary: Percentage of participants achieving a good/moderate European league against rheumatism (EULAR) response at Week 12 (Global Cohort)

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End point title

Percentage of participants achieving a good/moderate European league against rheumatism (EULAR) response at Week 12 (Global Cohort) ^[29]

End point description

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response was defined based on combination of current DAS28 score and improvement in current score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response, >0.6 to <=1.2:moderate response, <=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:moderate response, <=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:no response, <=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. For purpose of all analyses up to week 12, placebo arms were pooled into single arm to primarily serve as reference for comparison of active treatment arms. Analysis was performed on ITT set using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 12

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)	70.0	71.3	83.8	46.3

No statistical analyses for this end point

Secondary: Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[30]

End point description

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response was defined based on combination of current DAS28 score and improvement in current score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response, >0.6 to <=1.2:moderate response, <=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:moderate response, <=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:no response, <=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)
Week 24	79.8	80.5	90.4
Week 52	80.3	78.9	88.4

No statistical analyses for this end point

Secondary: Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Top of page

End point title

Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[31]

End point description

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response was defined based on combination of current DAS28 score and improvement in current score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response, >0.6 to <=1.2:moderate response, <=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:moderate response, <=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:no response, <=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Percentage of participants
number (not applicable)
Week 24	78.4	73.0	82.7
Week 52	74.5	81.1	81.5

No statistical analyses for this end point

Secondary: Number of participants achieving ACR/EULAR remission at Week 12 (Global Cohort)

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End point title

Number of participants achieving ACR/EULAR remission at Week 12 (Global Cohort) ^[32]

End point description

Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) <= 1, Swollen Joint Count 66 (SJC66) <= 1, high sensitivity C-reactive Protein (hsCRP) <= 1mg/dl and patient's global assessment of disease activity (PtGA) <= 10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set that includes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Participants	13	12	15	3

No statistical analyses for this end point

Secondary: Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[33]

End point description

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	497	477	247
Units: Participants
Week 24, n=497,477,247	21	18	28
Week 52, n=461,448,227	37	26	27

No statistical analyses for this end point

Secondary: Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Top of page

End point title

Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[34]

End point description

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	83	75	76
Units: Participants
Week 24, n=83,75,76	4	2	3
Week 52, n=74,68,67	8	4	7

No statistical analyses for this end point

Secondary: Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[35]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Percentage of participants
number (not applicable)
Week 24	84.6	89.9	92.7
Week 52	78.2	83.8	87.7

No statistical analyses for this end point

Secondary: Percentage of participants achieving no radiographic progression Van der Heijde modified total sharp scores (mTSS) <= 0.5) at Week 12 (Global Cohort)

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End point title

Percentage of participants achieving no radiographic progression Van der Heijde modified total sharp scores (mTSS) <= 0.5) at Week 12 (Global Cohort) ^[36]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 12

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Percentage of participants
number (not applicable)	88.2	92.7	94.1	85.8

No statistical analyses for this end point

Secondary: Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Top of page

End point title

Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[37]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Percentage of participants
number (not applicable)
Week 24	88.1	82.2	83.9
Week 52	85.6	71.9	87.9

No statistical analyses for this end point

Secondary: Change from Baseline in CDAI total score at Week 12 (Global Cohort)

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End point title

Change from Baseline in CDAI total score at Week 12 (Global Cohort) ^[38]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to 0-10 scale. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline. For the purpose of analyses up to week 12, the placebo arms were pooled into single placebo arm to primarily serve as reference for comparison of active treatment arms. Analysis was performed on ITT set. Multiple imputation method was used to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and week 12

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Scores on a scale
least squares mean (standard error)	-15.50 ± 0.680	-16.31 ± 0.678	-21.06 ± 0.878	-9.56 ± 0.896

No statistical analyses for this end point

Secondary: Change from Baseline in CDAI total score at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in CDAI total score at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[39]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale . CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: <The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Scores on a scale
least squares mean (standard error)
Week 24	-20.14 ± 0.669	-20.68 ± 0.677	-24.93 ± 0.848
Week 52	-20.84 ± 0.750	-21.14 ± 0.762	-24.87 ± 0.936

No statistical analyses for this end point

Secondary: Change from Baseline in CDAI total score at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in CDAI total score at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[40]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Scores on a scale
least squares mean (standard error)
Week 24	-20.26 ± 1.334	-16.78 ± 1.396	-20.60 ± 1.385
Week 52	-20.52 ± 1.472	-20.95 ± 1.547	-22.01 ± 1.545

No statistical analyses for this end point

Secondary: Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12 (Global Cohort)

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End point title

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12 (Global Cohort) ^[41]

End point description

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score range from 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Scores on a scale
least squares mean (standard error)
DAS28-CRP	-1.28 ± 0.064	-1.35 ± 0.064	-2.02 ± 0.082	-0.71 ± 0.085
DAS28-ESR	-1.34 ± 0.066	-1.40 ± 0.066	-1.95 ± 0.084	-0.73 ± 0.087

No statistical analyses for this end point

Secondary: Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[42]

End point description

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score range from 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Scores on a scale
least squares mean (standard error)
DAS28-CRP, Week 24	-1.65 ± 0.070	-1.71 ± 0.071	-2.45 ± 0.089
DAS28-CRP, Week 52	-1.77 ± 0.079	-1.76 ± 0.080	-2.40 ± 0.098
DAS28-ESR, Week 24	-1.73 ± 0.073	-1.79 ± 0.074	-2.40 ± 0.092
DAS28-ESR, Week 52	-1.87 ± 0.084	-1.82 ± 0.084	-2.38 ± 0.102

No statistical analyses for this end point

Secondary: Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[43]

End point description

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score range from 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Scores on a scale
least squares mean (standard error)
DAS28-CRP, Week 24	-1.76 ± 0.139	-1.39 ± 0.146	-1.88 ± 0.145
DAS28-CRP, Week 52	-1.81 ± 0.156	-1.70 ± 0.164	-1.97 ± 0.165
DAS28-ESR, Week 24	-1.88 ± 0.144	-1.48 ± 0.149	-1.93 ± 0.148
DAS28-ESR, Week 52	-1.88 ± 0.165	-1.74 ± 0.172	-1.96 ± 0.169

No statistical analyses for this end point

Secondary: Change from Baseline in Van der Heijde mTSS at Week 12 (Global Cohort)

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End point title

Change from Baseline in Van der Heijde mTSS at Week 12 (Global Cohort) ^[44]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: <The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Scores on a scale
least squares mean (standard error)	0.31 ± 0.072	0.15 ± 0.073	0.09 ± 0.092	0.13 ± 0.095

No statistical analyses for this end point

Secondary: Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Top of page

End point title

Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[45]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Scores on a scale
least squares mean (standard error)
Week 24	0.42 ± 0.092	0.32 ± 0.094	0.15 ± 0.115
Week 52	0.84 ± 0.148	0.46 ± 0.150	0.30 ± 0.184

No statistical analyses for this end point

Secondary: Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Top of page

End point title

Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[46]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Scores on a scale
least squares mean (standard error)
Week 24	0.18 ± 0.185	0.51 ± 0.196	0.21 ± 0.196
Week 52	-0.05 ± 0.288	0.76 ± 0.304	0.09 ± 0.307

No statistical analyses for this end point

Secondary: Change from Baseline in HAQ-DI at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in HAQ-DI at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[47]

End point description

HAQ-DI is a 20-question instrument that assesses the degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24

Notes
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Scores on a scale
least squares mean (standard error)
Week 24	-0.38 ± 0.033	-0.37 ± 0.033	-0.53 ± 0.041
Week 52	-0.40 ± 0.035	-0.37 ± 0.035	-0.52 ± 0.043

No statistical analyses for this end point

Secondary: Change from Baseline in HAQ-DI at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in HAQ-DI at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[48]

End point description

HAQ-DI is a 20-question instrument that assesses degree of difficulty of participant in accomplishing tasks in 8 functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of domain scores divided by number of domains answered. Total possible score ranges from 0 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. Negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 52

Notes
[48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Scores on a scale
least squares mean (standard error)
Week 24	-0.36 ± 0.065	-0.38 ± 0.067	-0.33 ± 0.067
Week 52	-0.30 ± 0.069	-0.37 ± 0.070	-0.40 ± 0.071

No statistical analyses for this end point

Secondary: Change from Baseline in Arthritis pain VAS at Week 12 (Global Cohort)

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End point title

Change from Baseline in Arthritis pain VAS at Week 12 (Global Cohort) ^[49]

End point description

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Scores on a scale
least squares mean (standard error)	-18.06 ± 1.266	-17.13 ± 1.256	-27.17 ± 1.610	-10.28 ± 1.657

No statistical analyses for this end point

Secondary: Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[50]

End point description

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24 and Week 52

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Scores on a scale
least squares mean (standard error)
Week 24	-23.32 ± 1.351	-22.32 ± 1.371	-31.27 ± 1.699
Week 52	-25.42 ± 1.506	-25.14 ± 1.525	-31.49 ± 1.846

No statistical analyses for this end point

Secondary: Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Top of page

End point title

Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[51]

End point description

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24 and Week 52

Notes
[51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Scores on a scale
least squares mean (standard error)
Week 24	-23.26 ± 2.710	-18.45 ± 2.793	-22.88 ± 2.791
Week 52	-23.71 ± 2.967	-21.72 ± 3.071	-21.62 ± 3.082

No statistical analyses for this end point

Secondary: Change from Baseline in Short form (SF)-36 physical component scores at Week 12 (Global Cohort)

Top of page

End point title

Change from Baseline in Short form (SF)-36 physical component scores at Week 12 (Global Cohort) ^[52]

End point description

SF-36 survey evaluates health-related quality of life, covering physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional issues,general health(GH),mental health,social functioning,vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health.Positive change from baseline, reported using T-score change, indicates improvement in overall physical health.Quality Metric software was used for scoring.Baseline was defined as most recent pre-dose NMV, including unscheduled visits.CB=subtracting PD value from BV.For analysis up to week 12, placebo arms were pooled into single arm to serve as reference for active treatment arm comparison.ITT set was analyzed using multiple imputation to manage missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: T-Score
least squares mean (standard error)	4.29 ± 0.363	4.48 ± 0.361	6.58 ± 0.464	2.05 ± 0.478

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 mental component scores at Week 12 (Global Cohort)

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End point title

Change from Baseline in SF-36 mental component scores at Week 12 (Global Cohort) ^[53]

End point description

SF-36 survey evaluates health-related quality of life, covering physical functioning,bodily pain,role limitations due to physical/emotional issues,general health,mental health(MH),social functioning(SF),vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.MCS is primarily derived from 4 domains(SF,MH,vitality,role-emotional) representing overall mental health.Positive change from baseline, reported using T-score change, indicates improvement in overall mental health.Quality Metric software was used for scoring.Baseline was defined as most recent pre-dose NMV, including unscheduled visits.CB=subtracting PD value from BV.For analysis up to week 12, placebo arms were pooled into single arm to serve as reference for active treatment arm comparison.ITT set was analyzed using multiple imputation to manage missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: T-Score
least squares mean (standard error)	2.24 ± 0.474	2.68 ± 0.471	3.56 ± 0.604	2.21 ± 0.624

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 domain scores at Week 12 (Global Cohort)

Top of page

End point title

Change from Baseline in SF-36 domain scores at Week 12 (Global Cohort) ^[54]

End point description

SF-36 is a health-related survey that assesses quality of life covering 8 domains: physical functioning (PF), bodily pain (BP), role limitations due to physical/emotional problems, general health (GH), mental health (MH), social functioning (SF), vitality. The MCS consists of 4 domains (SF, MH, vitality, role-emotional) and PCS consists of 4 domains (PF, role-physical, BP, GH). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. Positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed for participants with data available at the indicated time points.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	506	514	252	244
Units: Scores on a scale
least squares mean (standard error)
Bodily Pain, n=506,514,252,244	14.82 ± 20.264	16.13 ± 20.997	23.75 ± 22.916	9.21 ± 21.040
General Health, n=506,514,252,244	7.48 ± 16.025	6.74 ± 15.582	10.48 ± 15.647	5.16 ± 14.863
Mental Health, n=506,514,252,244	6.21 ± 17.655	6.96 ± 18.312	9.13 ± 19.229	4.88 ± 18.257
Physical Function, n=506,514,252,244	12.78 ± 19.321	14.47 ± 21.133	18.63 ± 20.724	8.42 ± 20.505
Role Emotional, n=506,514,252,244	6.41 ± 24.390	7.90 ± 25.675	9.85 ± 24.815	7.00 ± 23.912
Role Physical, n=506,514,252,244	12.08 ± 21.650	12.57 ± 22.044	17.66 ± 21.724	9.78 ± 20.593
Social Function, n=506,514,252,244	8.10 ± 23.132	9.75 ± 25.484	14.78 ± 25.900	6.76 ± 23.984
Vitality, n=506,514,252,244	8.99 ± 18.971	10.54 ± 19.349	15.18 ± 21.491	7.07 ± 18.624

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[55]

End point description

SF-36 survey evaluates health-related quality of life, covering physical functioning(PF) ,bodily pain(BP) ,role limitations due to physical/emotional issues, general health(GH), mental health, social functioning, vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains(PF, role-physical, BP, GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: T-Score
least squares mean (standard error)
Week 24	5.42 ± 0.416	5.24 ± 0.421	7.33 ± 0.520
Week 52	5.08 ± 0.460	5.06 ± 0.464	7.47 ± 0.569

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Top of page

End point title

Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[56]

End point description

SF-36 survey evaluates health-related quality of life, covering physical functioning, bodily pain, role limitations due to physical/emotional issues, general health, mental health(MH), social functioning(SF), vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains(SF, MH, vitality, role-emotional) representing overall mental health. Positive change from baseline, reported using T-score change, indicates improvement in overall mental health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: T-Score
least squares mean (standard error)
Week 24	2.69 ± 0.522	3.16 ± 0.528	4.80 ± 0.652
Week 52	3.06 ± 0.527	3.38 ± 0.530	4.08 ± 0.650

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Top of page

End point title

Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[57]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	494	486	249
Units: Scores on a scale
least squares mean (standard error)
Bodily Pain, Week 24, n=494,486,249	18.06 ± 21.568	18.87 ± 23.164	26.26 ± 24.870
Bodily Pain, Week 52, n=461,459,234	19.38 ± 22.807	20.50 ± 23.781	27.01 ± 24.068
General Health, Week 24, n=494,486,249	8.80 ± 17.357	8.18 ± 16.569	11.82 ± 18.258
General Health, Week 52, n=461,459,234	8.72 ± 17.635	8.74 ± 17.157	12.71 ± 18.374
Mental Health, Week 24, n=494,486,249	7.33 ± 18.871	7.81 ± 19.930	11.24 ± 19.875
Mental Health, Week 52, n=461,459,234	8.03 ± 18.819	8.21 ± 19.132	9.87 ± 19.417
Physical Function, Week 24, n=494,486,249	16.20 ± 21.646	16.59 ± 22.660	21.73 ± 23.769
Physical Function, Week 52, n=461,459,234	16.90 ± 21.458	17.40 ± 23.162	22.31 ± 26.462
Role Emotional, Week 24, n=494,486,249	8.33 ± 27.318	10.01 ± 24.860	13.45 ± 24.656
Role Emotional, Week 52, n=461,459,234	9.31 ± 24.987	10.77 ± 25.914	13.85 ± 25.643
Role Physical, Week 24, n=494,486,249	15.51 ± 22.052	15.60 ± 22.507	18.90 ± 22.618
Role Physical, Week 52, n=461,459,234	15.58 ± 23.558	16.29 ± 24.110	21.98 ± 24.671
Social Function, Week 24, n=494,486,249	10.25 ± 24.377	11.34 ± 26.893	15.91 ± 27.581
Social Function, Week 52, n=461,459,234	11.23 ± 24.368	12.06 ± 26.941	14.42 ± 27.313
Vitality, Week 24, n=494,486,249	11.21 ± 20.320	12.71 ± 20.389	18.02 ± 22.463
Vitality, Week 52, n=461,459,234	12.96 ± 20.197	12.58 ± 19.150	16.35 ± 22.327

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[58]

End point description

SF-36 survey evaluates health-related quality of life, covering physical functioning(PF), bodily pain(BP), role limitations due to physical/emotional issues, general health(GH), MH, SF, vitality. Each domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains(PF, role-physical, BP, GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data. For efficacy assessments baseline is interpreted as Day 1.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: T-Score
least squares mean (standard error)
Week 24	5.89 ± 0.821	4.36 ± 0.851	5.43 ± 0.857
Week 52	4.15 ± 0.902	4.89 ± 0.929	3.99 ± 0.941

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Top of page

End point title

Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[59]

End point description

SF-36 survey evaluates health-related quality of life, covering PF, BP, role limitations due to physical/emotional issues, GH, mental health(MH), social functioning(SF), vitality. Each domains is scored using average, 0-100; higher score represents better health. MCS was aggregated across domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains(SF, MH, vitality, role-emotional) representing overall mental health. Positive change from baseline, reported using T-score change, indicates improvement in overall mental health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data. For efficacy assessments baseline is interpreted as Day 1.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: T-Score
least squares mean (standard error)
Week 24	3.59 ± 1.041	4.37 ± 1.076	3.76 ± 1.082
Week 52	2.87 ± 1.051	4.53 ± 1.081	2.74 ± 1.092

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Top of page

End point title

Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[60]

End point description

SF-36 is a health-related survey that assesses quality of life covering 8 domains: physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health(MH),social functioning(SF),vitality. The MCS consists of 4 domains (SF,MH,vitality,role-emotional) and PCS consists of 4 domains (PF,role-physical,BP,GH). The individual question items are first summed, then domain scores are weighted to a scale between 0 to 100, where higher score represents better health. Positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline value. For efficacy assessments baseline is interpreted as Day 1. ITT set was analyzed for participants with data available at the indicated time points.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	82	76	75
Units: Scores on a scale
least squares mean (standard error)
Bodily Pain, Week 24, n=82,76,75	19.61 ± 22.430	17.93 ± 17.710	22.73 ± 21.012
Bodily Pain, Week 52, n=76,71,68	18.43 ± 23.444	19.35 ± 19.873	20.69 ± 23.501
General Health, Week 24, n=82,76,75	9.34 ± 13.259	8.96 ± 16.231	8.35 ± 17.087
General Health, Week 52, n=76,71,68	6.16 ± 15.885	10.52 ± 17.755	6.69 ± 16.707
Mental Health, Week 24, n=82,76,75	8.72 ± 19.623	10.20 ± 15.842	8.87 ± 19.270
Mental Health, Week 52, n=76,71,68	8.68 ± 19.585	12.25 ± 19.907	8.60 ± 19.256
Physical Function, Week 24, n=82,76,75	16.89 ± 20.407	17.30 ± 20.744	16.93 ± 21.433
Physical Function, Week 52, n=76,71,68	13.55 ± 24.025	19.72 ± 20.769	18.53 ± 20.608
Role Emotional, Week 24, n=82,76,75	9.35 ± 26.495	15.57 ± 25.325	11.44 ± 27.901
Role Emotional, Week 52, n=76,71,68	6.91 ± 27.467	16.78 ± 28.189	10.29 ± 28.907
Role Physical, Week 24, n=82,76,75	16.92 ± 22.168	17.02 ± 19.568	20.17 ± 21.197
Role Physical, Week 52, n=76,71,68	14.80 ± 23.581	20.86 ± 20.727	17.46 ± 24.087
Social Function, Week 24, n=82,76,75	12.80 ± 25.381	12.17 ± 25.247	14.33 ± 24.634
Social Function, Week 52, n=76,71,68	8.55 ± 29.312	16.20 ± 25.477	15.26 ± 24.131
Vitality, Week 24, n=82,76,75	14.25 ± 18.770	13.40 ± 18.839	13.67 ± 21.100
Vitality, Week 52, n=76,71,68	13.32 ± 19.826	12.50 ± 21.417	11.31 ± 20.581

No statistical analyses for this end point

Secondary: Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12 (Global Cohort)

Top of page

End point title

Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12 (Global Cohort) ^[61]

End point description

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	271	270
Units: Scores on a scale
least squares mean (standard error)	4.76 ± 0.482	4.91 ± 0.479	7.92 ± 0.615	3.68 ± 0.637

No statistical analyses for this end point

Secondary: Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Top of page

End point title

Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[62]

End point description

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Participants who received study intervention from Day 1 to Week 52 were analyzed. Missing data was handled by multiple imputation method.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	271
Units: Scores on a scale
least squares mean (standard error)
Week 24	6.10 ± 0.523	6.12 ± 0.528	8.37 ± 0.654
Week 52	6.97 ± 0.538	6.41 ± 0.543	8.38 ± 0.664

No statistical analyses for this end point

Secondary: Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Top of page

End point title

Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[63]

End point description

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1. The analysis was performed on all randomized participants in ITT set. Analysis was performed using multiple imputation method to handle missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	91	89	90
Units: Scores on a scale
least squares mean (standard error)
Week 24	6.95 ± 1.034	6.08 ± 1.072	6.87 ± 1.070
Week 52	5.73 ± 1.061	6.50 ± 1.096	6.01 ± 1.105

No statistical analyses for this end point

Secondary: Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) (Global Cohort)

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End point title

Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) (Global Cohort) ^[64]

End point description

AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with use of a study intervention, whether or not considered related to study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs were included. Fifteen participants in Pooled placebo received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm. The analysis was performed on Safety Set that includes all randomized participants who received at least one dose of study treatment. Pooled Placebo collected data from Day 01 to Week 12. Placebo switched arms collected data from Week 12 to 59. Experimental arms collected data from Day 01 to Week 59.

End point type

Secondary

End point timeframe

Up to Week 59

Notes
[64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	286	255
Units: Participants
AE	420	408	127	127
SAE	44	43	6	6
AESI	72	75	5	5

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of white blood cell (WBC) count, platelet count, neutrophils, lymphocytes at Week 12 (Giga cells per liter) (Global Cohort)

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End point title

Change from Baseline in hematology parameter of white blood cell (WBC) count, platelet count, neutrophils, lymphocytes at Week 12 (Giga cells per liter) (Global Cohort) ^[65]

End point description

Blood samples were collected for the assessment of change from baseline in hematology parameters including WBC count, platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	494	490	267	229
Units: Giga cells per liter (10^9/L)
arithmetic mean (standard deviation)
Lymphocytes	0.002 ± 0.5235	-0.019 ± 0.5304	0.045 ± 0.5477	-0.011 ± 0.4783
Neutrophils	-0.444 ± 1.8305	-0.647 ± 1.9192	-1.054 ± 2.1874	0.053 ± 1.9956
Platelets	-19.0 ± 50.74	-19.9 ± 53.15	-34.3 ± 64.33	0.8 ± 54.75
Leukocytes	-0.45 ± 1.919	-0.70 ± 1.992	-1.02 ± 2.215	0.02 ± 1.984

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of WBC count, platelet count, neutrophils, lymphocytes at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in hematology parameter of WBC count, platelet count, neutrophils, lymphocytes at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[66]

End point description

Blood samples were collected for the assessment of change from baseline in hematology parameters including WBC count, platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	497	480	255
Units: Giga cells per liter (10^9/L)
arithmetic mean (standard deviation)
Lymphocytes, Week 24	0.004 ± 0.5092	-0.017 ± 0.5188	2.215 ± 0.5294
Lymphocytes, Week 52	0.001 ± 0.5679	-0.012 ± 0.5487	-0.143 ± 0.5739
Neutrophils, Week 24	-0.508 ± 1.7714	-0.647 ± 2.0762	-1.135 ± 2.2376
Neutrophils, Week 52	-0.594 ± 1.8490	-0.788 ± 2.1627	-1.022 ± 2.4346
Platelets, Week 24	-16.4 ± 61.73	-21.0 ± 56.36	-32.0 ± 63.74
Platelets, Week 52	-24.9 ± 66.31	-22.0 ± 63.94	-37.6 ± 70.56
Leukocytes, Week 24	-0.50 ± 1.818	-0.66 ± 2.129	-1.17 ± 2.269
Leukocytes, Week 52	-0.59 ± 1.976	-0.80 ± 2.346	-1.22 ± 2.465

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of WBC count, platelet count, neutrophils, lymphocytes at Week 24 and Week 52 (Global Cohort)

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End point title

Change from Baseline in hematology parameter of WBC count, platelet count, neutrophils, lymphocytes at Week 24 and Week 52 (Global Cohort) ^[67]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[67] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	80	74	64
Units: Giga cells per liter (10^9/L)
arithmetic mean (standard deviation)
Lymphocytes, Week 24	-0.072 ± 0.4236	0.014 ± 0.5442	-0.042 ± 0.5563
Lymphocytes, Week 52	-0.085 ± 0.5077	-0.071 ± 0.5098	-0.243 ± 0.6030
Neutrophils, Week 24	-0.582 ± 1.6685	-0.255 ± 2.1106	-0.745 ± 1.9306
Neutrophils, Week 52	-0.605 ± 1.8343	-0.288 ± 2.2031	-0.617 ± 2.1111
Platelets, Week 24	-11.6 ± 58.77	-13.6 ± 40.78	-36.1 ± 62.88
Platelets, Week 52	-17.8 ± 39.56	-21.1 ± 44.72	-27.8 ± 72.75
Leukocytes, Week 24	-0.64 ± 1.669	-0.25 ± 2.204	-0.84 ± 2.093
Leukocytes, Week 52	-0.65 ± 2.148	-0.38 ± 2.259	-0.94 ± 2.134

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of hemoglobin at Week 12 (Global Cohort)

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End point title

Change from Baseline in hematology parameter of hemoglobin at Week 12 (Global Cohort) ^[68]

End point description

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	492	489	267	231
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)	0.8 ± 7.50	0.1 ± 7.57	0.4 ± 8.53	-1.0 ± 7.57

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[69]

End point description

Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	497	479	255
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Week 24	0.5 ± 8.89	1.0 ± 8.57	1.9 ± 9.23
Week 52	0.6 ± 10.83	0.0 ± 10.12	1.0 ± 10.35

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), Gamma-Glutamyl transpeptidase (GGT) at Week 12 (Global Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), Gamma-Glutamyl transpeptidase (GGT) at Week 12 (Global Cohort) ^[70]

End point description

Blood samples were collected for the assessment of clinical chemistry parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) and gamma-glutamyl transferase (GGT) levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	511	504	273	231
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
AP	-1.3 ± 19.79	0.4 ± 28.71	-5.1 ± 19.95	-1.6 ± 22.96
ALT	0.8 ± 14.14	1.2 ± 13.49	3.0 ± 15.73	0.3 ± 15.88
AST	1.3 ± 8.34	2.0 ± 11.35	3.8 ± 12.23	-0.1 ± 8.73
GGT	-1.5 ± 20.77	0.3 ± 44.60	-1.1 ± 17.60	-1.7 ± 25.38

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[71]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	79	74	64
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Week 24	1.2 ± 6.36	1.2 ± 6.10	3.2 ± 9.01
Week 52	0.8 ± 7.96	1.8 ± 8.99	2.1 ± 10.14

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[72]

End point description

Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	497	480	257
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
AP, Week 24	-0.3 ± 23.40	0.6 ± 20.47	-7.9 ± 24.03
AP, Week 52	0.3 ± 20.20	1.4 ± 22.40	-5.1 ± 23.34
ALT, Week 24	1.0 ± 18.23	4.6 ± 63.38	4.1 ± 21.70
ALT, Week 52	-0.1 ± 14.16	2.0 ± 16.35	3.7 ± 15.33
AST, Week 24	1.2 ± 9.71	3.8 ± 45.20	4.2 ± 13.20
AST, Week 52	1.0 ± 8.08	2.0 ± 11.47	3.9 ± 11.17
GGT, Week 24	-1.2 ± 25.56	0.5 ± 32.53	-1.6 ± 16.76
GGT, Week 52	-1.0 ± 24.25	0.2 ± 22.40	-0.1 ± 17.49

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[73]

End point description

Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	83	74	64
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
AP, Week 24	-0.3 ± 15.77	-3.5 ± 19.93	-2.8 ± 23.41
AP, Week 52	-2.8 ± 19.07	-1.6 ± 27.58	-2.7 ± 26.76
ALT, Week 24	-0.2 ± 14.86	0.2 ± 14.15	6.4 ± 15.92
ALT, Week 52	1.0 ± 20.01	0.7 ± 13.66	7.8 ± 24.01
AST, Week 24	-0.2 ± 10.16	1.4 ± 6.42	5.0 ± 9.96
AST, Week 52	1.3 ± 14.54	2.2 ± 7.07	7.0 ± 16.92
GGT, Week 24	0.8 ± 20.15	-2.0 ± 18.05	0.0 ± 25.57
GGT, Week 52	-2.1 ± 15.84	-1.1 ± 16.29	0.8 ± 23.66

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of total bilirubin at Week 12 (Global Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 12 (Global Cohort) ^[74]

End point description

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	506	499	271	231
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)	0.3 ± 2.84	0.5 ± 2.68	0.5 ± 3.11	0.2 ± 2.78

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[75]

End point description

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	496	477	256
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)
Week 24	0.5 ± 2.66	0.5 ± 2.78	0.6 ± 2.73
Week 52	0.3 ± 2.66	0.6 ± 2.80	0.9 ± 2.83

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[76]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	81	73	64
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)
Week 24	0.3 ± 3.07	0.3 ± 2.06	0.4 ± 2.79
Week 52	-0.1 ± 2.88	0.6 ± 2.44	0.4 ± 2.20

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of albumin at Week 12 (Global Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of albumin at Week 12 (Global Cohort) ^[77]

End point description

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	511	504	273	231
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)	0.1 ± 2.56	0.1 ± 2.49	1.1 ± 2.60	-0.3 ± 2.72

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[78]

End point description

Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	497	479	257
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Week 24	0.2 ± 2.72	0.3 ± 2.59	1.6 ± 2.95
Week 52	0.3 ± 2.77	0.3 ± 2.88	1.3 ± 3.03

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for placebo switched arms (Global Cohort) ^[79]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	83	74	64
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Week 24	0.1 ± 2.33	0.6 ± 2.13	2.5 ± 2.99
Week 52	-0.0 ± 2.87	0.9 ± 2.64	2.1 ± 3.22

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 12 (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 12 (Global Cohort) ^[80]

End point description

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 4 and not Week 12 as no data collected. Week 4 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	0 ^[81]	0 ^[82]	0 ^[83]	0 ^[84]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±	±

Notes
[81] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[82] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[83] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[84] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for placebo switched arms (Global Cohort) ^[85]

End point description

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Week 12) and Week 24

Notes
[85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	0 ^[86]	0 ^[87]	0 ^[88]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[86] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[87] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[88] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[89]

End point description

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24

Notes
[89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	0 ^[90]	0 ^[91]	0 ^[92]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[90] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[91] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[92] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[93]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 52

Notes
[93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	438	437	226
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	0.121 ± 0.8198	0.129 ± 0.8076	0.402 ± 0.8794

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for placebo switched arms (Global Cohort) ^[94]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 4) and Week 52

Notes
[94] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	71	66	55
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	0.198 ± 0.9586	0.255 ± 0.8086	0.691 ± 0.9233

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)-cholesterol at Week 12 (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)-cholesterol at Week 12 (Global Cohort) ^[95]

End point description

Blood samples were collected for assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For purpose of all analyses up to week 12, placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for lipid panel is Week 4 and not Week 12 as no data collected. Week 4 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	0 ^[96]	0 ^[97]	0 ^[98]	0 ^[99]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±	±

Notes
[96] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[97] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[98] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[99] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[100]

End point description

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24

Notes
[100] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	0 ^[101]	0 ^[102]	0 ^[103]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[101] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[102] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[103] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for placebo switched arms (Global Cohort) ^[104]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 12) and Week 24

Notes
[104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	0 ^[105]	0 ^[106]	0 ^[107]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[105] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[106] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[107] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[108]

End point description

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 52

Notes
[108] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	438	437	226
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
HDL Cholesterol, Direct, n=438,437,226	0.026 ± 0.2415	0.010 ± 0.2812	0.157 ± 0.3184
LDL Cholesterol, n=432,436,226	0.076 ± 0.6971	0.093 ± 0.6396	0.191 ± 0.7423

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for placebo switched arms (Global Cohort) ^[109]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 4) and Week 52

Notes
[109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	71	66	55
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
HDL Cholesterol, Direct, n=71,66,55	-0.041 ± 0.2841	0.045 ± 0.2769	0.135 ± 0.3094
LDL Cholesterol, n=71,65,55	0.188 ± 0.7796	0.184 ± 0.6039	0.495 ± 0.7375

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 12 (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 12 (Global Cohort) ^[110]

End point description

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Blood samples were collected at indicated time points as per schedule of assessment in the protocol. The Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for the lipid panel, there is no corresponding time point in the schedule of assessment. Consequently, the only objective that can be assessed for the lipid panel is Week 4 and not at Week 12.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	0 ^[111]	0 ^[112]	0 ^[113]	0 ^[114]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±	±

Notes
[111] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[112] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[113] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[114] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 24 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 24 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[115]

End point description

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24

Notes
[115] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	0 ^[116]	0 ^[117]	0 ^[118]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[116] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[117] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[118] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 24 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 24 for placebo switched arms (Global Cohort) ^[119]

End point description

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Week 12) and Week 24

Notes
[119] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	0 ^[120]	0 ^[121]	0 ^[122]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[120] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[121] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[122] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) ^[123]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 52

Notes
[123] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	438	437	226
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	0.045 ± 0.5902	0.054 ± 0.5970	0.117 ± 0.6444

No statistical analyses for this end point

Secondary: Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities (Global Cohort)

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End point title

Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities (Global Cohort) ^[124]

End point description

Number of participants with NCI-CTCAE >=Grade 3 hematological/clinical chemistry abnormalities were summarized. Hematological and Clinical chemistry parameters were summarized according to the NCI-CTCAE, version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Data is presented for only those parameters for which participants had worst case >=Grade 3 shifts from Baseline. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study treatment. Pooled Placebo collected data till Week 12. Placebo switched arms collected data from Week 12 to 59. Experimental arm collected data from Day 01 to Week 59.

End point type

Secondary

End point timeframe

Up to Week 59

Notes
[124] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)
Number of subjects analysed	545	539	286	255
Units: Participants
Alanine aminotransferase increased,Total,Grade 3	4	5	4	1
Aspartate aminotransferase increased,Total,Grade3	2	3	1	1
Anemia, Total, Grade 3	3	5	2	2
Lymphocyte count decreased, Grade 3	9	11	9	3
Neutrophil count decreased, Total, Grade 3	3	3	2	2
Lymphocyte count decreased, Grade 4	0	0	9	0
Hypertriglyceridemia, Total, Grade 3	10	0	2	0
Aspartate aminotransferase increased,Total,Grade4	0	2	0	0
Alanine aminotransferase increased, Total, Grade 4	0	2	0	0
Creatinine increased, Total, Grade 4	1	0	0	0
Chronic Kidney Disease, Total, Grade 3	0	1	2	0
Chronic Kidney Disease, Total, Grade 4	1	0	0	0
Hemoglobin increased, Total, Grade 3	1	0	0	0
White blood cell decreased, Total, Grade 3	2	0	0	0
Neutrophil count decreased, Total, Grade 4	2	1	0	0
Hypertriglyceridemia, Total, Grade 4	1	0	0	0

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 52 for placebo switched arms (Global Cohort)

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End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 52 for placebo switched arms (Global Cohort) ^[125]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 4) and Week 52

Notes
[125] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	71	66	55
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	0.111 ± 0.4371	0.034 ± 0.5246	0.129 ± 0.5816

No statistical analyses for this end point

Secondary: Concentrations of Granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody (Global Cohort)

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End point title

Concentrations of Granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody (Global Cohort) ^[126]

End point description

Blood samples were collected for markers which may influence rheumatoid arthritis. Concentrations of GM-CSF autoantibodies was determined. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis.

End point type

Secondary

End point timeframe

At baseline

Notes
[126] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	91	89	75	286
Units: Microgram per liter (ug/L)
arithmetic mean (standard deviation)	201.587 ± 519.9638	193.911 ± 402.0018	217.622 ± 399.6172	267.669 ± 642.5823	252.209 ± 671.7397	189.505 ± 344.7866

No statistical analyses for this end point

Secondary: Number of participants with anti-GSK3196165 antibodies (Global Cohort)

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End point title

Number of participants with anti-GSK3196165 antibodies (Global Cohort) ^[127]

End point description

Serum samples were collected for the determination of anti-GSK3196165 antibodies (ADA) using a validated electrochemiluminescence (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. The analysis was performed on the Safety set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis.

End point type

Secondary

End point timeframe

Up to Week 52

Notes
[127] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)
Number of subjects analysed	545	539	91	89	75	286
Units: Participants	6	6	3	1	0	0

No statistical analyses for this end point

Secondary: Percentage of participants achieving Clinical disease activity index (CDAI) total score less than or equal to (<=)10 [CDAI Low disease activity (LDA)] at Week 12 (Asia Cohort)

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End point title

Percentage of participants achieving Clinical disease activity index (CDAI) total score less than or equal to (<=)10 [CDAI Low disease activity (LDA)] at Week 12 (Asia Cohort) ^[128]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale [VAS] with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. For the purpose of all analyses up to week 12, the placebo arms were pooled into single placebo arm to primarily serve as reference for the comparison of active treatment arms. Percentage values are rounded off. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[128] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	43	19	21
Units: Percentage of participants	13	12	58	19

No statistical analyses for this end point

Secondary: Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Asia Cohort)

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End point title

Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Asia Cohort) ^[129]

End point description

Health Assessment Questionnaire-Disability Index (HAQ-DI) is 20-question instrument that assesses degree of difficulty in accomplishing tasks in eight functional areas:dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score is sum of domain scores divided by number of domains answered. The score ranges from 0 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline.Placebo arms were pooled into single placebo arm to primarily serve as reference for comparison of active treatment arms. Analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[129] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	46	42	19	21
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.22 ± 0.479	-0.25 ± 0.537	-0.47 ± 0.281	0.02 ± 0.577

No statistical analyses for this end point

Secondary: Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[130]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale [VAS] with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[130] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Percentage of participants
number (not applicable)
Week 24, n=38,43,17	21.0	19.0	53.0
Week 52, n-3,32,15	45.0	41.0	47.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[131]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[131] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Percentage of participants
number (not applicable)
Week 24, n=6,6,7	33.0	33.0	43.0
Week 52, n=4,6,5	75.0	67.0	40.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 (Asia Cohort)

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End point title

Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 (Asia Cohort) ^[132]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale [VAS] with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. For the purpose of all analyses up to week 12, the placebo arms were pooled into single placebo arm to primarily serve as reference for the comparison of active treatment arms. Percentage values are rounded off. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[132] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	43	19	21
Units: Percentage of participants
number (not applicable)	2.0	0.0	11.0	0.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[133]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[133] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Percentage of participants
number (not applicable)
Week 24, n=38,43,17	0.0	7.0	24.0
Week 52, n=31,32,15	6.0	16.0	13.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[134]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[134] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Percentage of participants
number (not applicable)
Week 24, n=6,6,7	0.0	0.0	0.0
Week 52, n=4,6,5	25.0	0.0	20.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving 50%/70% improvement in American College of Rheumatology Criteria(ACR50/70) at Week 12 (Asia Cohort)

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End point title

Percentage of participants achieving 50%/70% improvement in American College of Rheumatology Criteria(ACR50/70) at Week 12 (Asia Cohort) ^[135]

End point description

ACR50/70 is calculated as 50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and 50%/70% improvement in 3 of the following 5 measures:Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) [VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 = least difficulty to 3 = extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP)]. For the purpose of all analyses up to week 12, placebo arms were pooled into single placebo arm to primarily serve as reference for comparison of active treatment arms. Percentage values are rounded off. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[135] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	44	42	19	21
Units: Percentage of participants
number (not applicable)
ACR50	11.0	12.0	53.0	0.0
ACR70	5.0	2.0	16.0	0.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving ACR20/50/70 at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Percentage of participants achieving ACR20/50/70 at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[136]

End point description

ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) [VAS with values from 0=best to 100=worst], Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ- DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein mg/L (hsCRP)]. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[136] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	37	42	17
Units: Percentage of participants
number (not applicable)
ACR20, Week 24, n=37,42,17	54.0	55.0	19.0
ACR20, Week 52, n=30,31,15	63.0	77.0	87.0
ACR50, Week 24, n=37,42,17	19.0	24.0	53.0
ACR50, Week 52, n=30,31,15	37.0	48.0	53.0
ACR70, Week 24, n=37,42,17	8.0	7.0	29.0
ACR70, Week 52, n=30,31,15	13.0	10.0	27.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving ACR20/50/70 at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Percentage of participants achieving ACR20/50/70 at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[137]

End point description

ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) [VAS with values from 0=best to 100=worst], Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ- DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein mg/L (hsCRP)]. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[137] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Percentage of participants
number (not applicable)
ACR20, Week 52, n=4,6,6	75.0	33.0	67.0
ACR50, Week 24, n=6,6,7	0.0	0.0	43.0
ACR50, Week 52, n=4,6,6	50.0	17.0	67.0
ACR70, Week 24, n=6,6,7	0.0	0.0	14.0
ACR70, Week 52, n=4,6,6	50.0	17.0	17.0
ACR20, Week 24, n=6,6,7	33.0	17.0	38.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 (Asia Cohort)

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End point title

Percentage of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 (Asia Cohort) ^[138]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Percentage values are rounded off. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[138] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	43	19	21
Units: Percentage of participants
number (not applicable)	20.0	9.0	47.0	10.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 (Asia Cohort)

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End point title

Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 (Asia Cohort) ^[139]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Percentage values are rounded off. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[139] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	42	19	21
Units: Percentage of participants
number (not applicable)	16.0	21.0	58.0	10.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[140]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[140] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Percentage of participants
number (not applicable)
Week 24, n=38,43,17	24.0	21.0	53.0
Week 52, n=31,32,15	39.0	34.0	67.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

Top of page

End point title

Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[141]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[141] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Percentage of participants
number (not applicable)
Week 24, n=38,43,17	16.0	16.0	47.0
Week 52, n=28,30,15	25.0	20.0	47.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[142]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[142] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Percentage of participants
number (not applicable)
Week 24, n=6,6,7	33.0	0.0	29.0
Week 52, n=4,6,6	50.0	0.0	17.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[143]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[143] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Percentage of participants
number (not applicable)
Week 24, n=6,6,7	33.0	33.0	43.0
Week 52, n=4,6,6	75.0	50.0	67.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 (Asia Cohort)

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End point title

Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 (Asia Cohort) ^[144]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Percentage values are rounded off. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[144] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	42	19	21
Units: Percentage of participants
number (not applicable)	11.0	5.0	42.0	10.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[145]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[145] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Percentage of participants
number (not applicable)
Week 24, n=38,43,17	13.0	19.0	41.0
Week 52, n=31,32,15	19.0	25.0	53.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 (Asia Cohort)

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End point title

Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 (Asia Cohort) ^[146]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Percentage values are rounded off. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[146] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	43	19	21
Units: Percentage of participants
number (not applicable)	2.0	2.0	21.0	0.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[147]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[147] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Percentage of participants
number (not applicable)
Week 24, n=38,43,17	8.0	12.0	29.0
Week 52, n=28,30,15	7.0	17.0	20.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[148]

End point description

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[148] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Percentage of participants
number (not applicable)
Week 24, n=6,6,7	33.0	0.0	29.0
Week 52, n=4,6,6	50.0	17.0	17.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[149]

End point description

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[149] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Percentage of participants
number (not applicable)
Week 24, n=6,6,7	0.0	0.0	0.0
Week 52, n=4,6,6	25.0	0.0	17.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving a good/moderate European league against rheumatism (EULAR) response at Week 12 (Asia Cohort)

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End point title

Percentage of participants achieving a good/moderate European league against rheumatism (EULAR) response at Week 12 (Asia Cohort) ^[150]

End point description

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response was defined based on combination of current DAS28 score and improvement in current score relative to Baseline. The definition of no response, moderate response and good response was; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response, >0.6 to <=1.2:moderate response, <=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:moderate response, <=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:no response, <=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then corresponding EULAR category was set to missing. Placebo arms were pooled into single arm to serve as reference for comparison to active treatment arms. Percentage values are rounded off. Analysis was performed on ITT-Supplementary Asia Cohort with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[150] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	44	41	19	21
Units: Percentage of participants
number (not applicable)	66.0	61.0	84.0	33.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[151]

End point description

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response was defined based on combination of current DAS28 score and improvement in current score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response, >0.6 to <=1.2:moderate response, <=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:moderate response, <=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:no response, <=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[151] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	37	42	17
Units: Percentage of participants
number (not applicable)
Week 24, n=37,42,17	65.0	64.0	94.0
Week 52, n-30,31,15	70.0	84.0	100.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[152]

End point description

DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response was defined based on combination of current DAS28 score and improvement in current score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response, >0.6 to <=1.2:moderate response, <=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:moderate response, <=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:no response, <=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Week 12 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[152] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Percentage of participants
number (not applicable)
Week 24, n=6,6,7	50.0	50.0	100.0
Week 52, n=4,6,6	100.0	100.0	100.0

No statistical analyses for this end point

Secondary: Number of participants achieving ACR/EULAR remission at Week 12 (Asia Cohort)

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End point title

Number of participants achieving ACR/EULAR remission at Week 12 (Asia Cohort) ^[153]

End point description

Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) <= 1, Swollen Joint Count 66 (SJC66) <= 1, high sensitivity C-reactive Protein (hsCRP) <= 1mg/dl and patient's global assessment of disease activity (PtGA) <= 10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[153] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	42	19	21
Units: Participants	2	0	2	0

No statistical analyses for this end point

Secondary: Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[154]

End point description

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[154] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Participants
Week 24, n=38,43,17	0	0	3
Week 52, n=31,32,15	0	2	2

No statistical analyses for this end point

Secondary: Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[155]

End point description

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[155] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Participants
Week 24, n=6,6,7	0	0	1
Week 52, n=4,6,6	0	0	0

No statistical analyses for this end point

Secondary: Percentage of participants achieving no radiographic progression Van der Heijde modified total sharp scores (mTSS) <= 0.5) at Week 12 (Asia Cohort)

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End point title

Percentage of participants achieving no radiographic progression Van der Heijde modified total sharp scores (mTSS) <= 0.5) at Week 12 (Asia Cohort) ^[156]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Percentage values are rounded off. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 12

Notes
[156] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	9	6	3	2
Units: Percentage of participants	67	67	67	50

No statistical analyses for this end point

Secondary: Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[157]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[157] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	5	2
Units: Percentage of participants
Week 24, n=6,5,2	83	60	50
Week 52, n=5,3,2	40	100	50

No statistical analyses for this end point

Secondary: Change from Baseline in CDAI total score at Week 12 (Asia Cohort)

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End point title

Change from Baseline in CDAI total score at Week 12 (Asia Cohort) ^[158]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale . CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a NMV, including from unscheduled visits. Change from Baseline was calculated by subtracting PDV from BV. For the purpose of analyses up to week 12, the placebo arms were pooled into single placebo arm to primarily serve as reference for comparison of active treatment arms. Analysis was performed on ITT-Supplementary Asia Cohort with data available at indicated timepoints were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and week 12

Notes
[158] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	44	42	19	21
Units: Scores on a scale
arithmetic mean (standard deviation)	-13.75 ± 10.935	-10.91 ± 11.649	-19.47 ± 12.718	-4.38 ± 8.640

No statistical analyses for this end point

Secondary: Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[159]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. Percentage values are rounded off. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Week 24 and Week 52

Notes
[159] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	1	1	0 ^[160]
Units: Percentage of participants
Week 24, n=1,1,0	0	100
Week 52, n=1,1,0	0	100

Notes
[160] - No participant was analyzed at the timepoints Week 24 and Week 52.

No statistical analyses for this end point

Secondary: Change from Baseline in CDAI total score at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in CDAI total score at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[161]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale . CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a NMV, including from unscheduled visits. Change from Baseline was calculated by subtracting PDV from BV. Analysis was performed on participants who received study intervention from Day 01 to Week 52 IN Asia Cohort with data available at indicated timepoints were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[161] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	37	42	17
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=37,42,17	-15.27 ± 12.329	-13.39 ± 10.575	-21.44 ± 11.208
Week 52, n=30,31,15	-18.29 ± 13.199	-19.35 ± 13.923	-23.21 ± 12.303

No statistical analyses for this end point

Secondary: Change from Baseline in CDAI total score at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in CDAI total score at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[162]

End point description

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale . CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a NMV, including from unscheduled visits. Change from Baseline was calculated by subtracting PDV from BV. For efficacy assessments baseline is interpreted as Day 1. Analysis was performed on participants who received study intervention from Week 12 to Week 52 IN Asia Cohort with data available at indicated timepoints were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[162] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=6,6,7	-8.78 ± 6.086	-12.28 ± 10.842	-20.47 ± 12.133
Week 52, n=4,6,5	-16.28 ± 5.351	-17.47 ± 11.166	-23.18 ± 13.070

No statistical analyses for this end point

Secondary: Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12 (Asia Cohort)

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End point title

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12 (Asia Cohort) ^[163]

End point description

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in milimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[163] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	44	42	19	21
Units: Scores on a scale
arithmetic mean (standard deviation)
DAS28-CRP, n=44,41,19,21	-1.26 ± 1.034	-1.05 ± 0.968	-2.27 ± 1.089	-0.47 ± 0.950
DAS28-ESR, n=44,42,19,21	-1.33 ± 1.023	-1.11 ± 0.964	-2.15 ± 1.161	-0.40 ± 0.937

No statistical analyses for this end point

Secondary: Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[164]

End point description

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in milimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[164] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	37	42	17
Units: Scores on a scale
arithmetic mean (standard deviation)
DAS28-CRP, Week 24, n=37,42,17	-1.41 ± 1.221	-1.28 ± 1.086	-2.29 ± 1.037
DAS28-CRP, Week 52, n=30,31,15	-1.63 ± 1.353	-1.82 ± 1.262	-2.47 ± 1.253
DAS28-ESR, Week 24, n=37,42,17	-1.50 ± 1.153	-1.27 ± 1.121	-2.30 ± 1.246
DAS28-ESR, Week 52, n=28,29,15	-1.76 ± 1.358	-1.84 ± 1.303	-2.42 ± 1.318

No statistical analyses for this end point

Secondary: Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[165]

End point description

DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in milimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[165] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Scores on a scale
arithmetic mean (standard deviation)
DAS28-CRP, Week 24, n=6,6,7	-1.27 ± 1.171	-1.08 ± 0.852	-2.14 ± 1.242
DAS28-CRP, Week 52, n=4,6,6	-2.24 ± 1.200	-1.52 ± 1.005	-2.63 ± 1.244
DAS28-ESR, Week 24, n=6,6,7	-0.91 ± 1.216	-0.99 ± 0.897	-2.06 ± 1.053
DAS28-ESR, Week 52, n=4,6,6	-1.82 ± 1.183	-1.46 ± 0.912	-2.48 ± 1.186

No statistical analyses for this end point

Secondary: Change from Baseline in Van der Heijde mTSS at Week 12 (Asia Cohort)

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End point title

Change from Baseline in Van der Heijde mTSS at Week 12 (Asia Cohort) ^[166]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[166] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	9	6	3	2
Units: Scores on a scale
arithmetic mean (standard deviation)	1.22 ± 2.476	3.42 ± 7.889	0.33 ± 0.577	0.25 ± 0.354

No statistical analyses for this end point

Secondary: Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[167]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[167] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	5	2
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=6,5,2	-0.08 ± 0.665	5.60 ± 10.922	0.50 ± 0.707
Week 52, n=5,3,2	1.40 ± 1.673	0.00 ± 0.000	0.50 ± 0.707

No statistical analyses for this end point

Secondary: Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[168]

End point description

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[168] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	1 ^[169]	1 ^[170]	0 ^[171]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=1,1,0	0.50 ± 0	0.00 ± 0	±
Week 52, n=1,1,0	0.50 ± 0	0.00 ± 0	±

Notes
[169] - Standard deviation data was not derived as only one participant was analyzed.
[170] - Standard deviation data was not derived as only one participant was analyzed.
[171] - No participant was analyzed at the timepoints Week 24 and Week 52.

No statistical analyses for this end point

Secondary: Change from Baseline in HAQ-DI at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in HAQ-DI at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[172]

End point description

HAQ-DI is a 20-question instrument that assesses the degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24

Notes
[172] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	42	17
Units: Scores on a scale
arithmetic mean (standard deviation)
HAQ-Disability Index, Week 24, n=38,42,17	-0.25 ± 0.569	-0.29 ± 0.524	-0.48 ± 0.266
HAQ-Disability Index, Week 52, n=32,31,15	-0.36 ± 0.573	-0.40 ± 0.604	-0.59 ± 0.483

No statistical analyses for this end point

Secondary: Change from Baseline in HAQ-DI at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in HAQ-DI at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[173]

End point description

HAQ-DI is a 20-question instrument that assesses degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of domain scores divided by number of domains answered. Total possible score ranges from 0 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. Negative change from baseline indicates an improvement. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1. Analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 52

Notes
[173] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Scores on a scale
arithmetic mean (standard deviation)
HAQ-Disability Index, Week 24, n=6,6,7	-0.33 ± 0.921	-0.02 ± 0.436	-0.46 ± 0.431
HAQ-Disability Index, Week 52, n=4,6,7	-0.19 ± 1.139	-0.19 ± 0.438	-0.52 ± 0.442

No statistical analyses for this end point

Secondary: Change from Baseline in Arthritis pain VAS at Week 12 (Asia Cohort)

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End point title

Change from Baseline in Arthritis pain VAS at Week 12 (Asia Cohort) ^[174]

End point description

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[174] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	46	42	19	21
Units: Scores on a scale
arithmetic mean (standard deviation)	-20.0 ± 22.57	-18.0 ± 25.37	-21.2 ± 22.91	-1.8 ± 21.00

No statistical analyses for this end point

Secondary: Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[175]

End point description

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24 and Week 52

Notes
[175] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	42	17
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=38,42,17	-24.4 ± 22.90	-25.2 ± 25.71	-32.9 ± 25.97
Week 52, n=32,31,15	-30.4 ± 26.98	-27.9 ± 23.51	-33.0 ± 23.04

No statistical analyses for this end point

Secondary: Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[176]

End point description

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24 and Week 52

Notes
[176] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=6,6,7	-14.2 ± 20.71	-13.5 ± 27.57	-27.0 ± 21.86
Week 52, n=4,6,7	-32.3 ± 14.45	-21.8 ± 34.17	-34.4 ± 27.50

No statistical analyses for this end point

Secondary: Change from Baseline in Short form (SF)-36 physical component scores at Week 12 (Asia Cohort)

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End point title

Change from Baseline in Short form (SF)-36 physical component scores at Week 12 (Asia Cohort) ^[177]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[177] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	42	19	21
Units: T-Score
arithmetic mean (standard deviation)	4.051 ± 6.1927	3.040 ± 5.8359	8.312 ± 6.6143	0.222 ± 4.5222

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 mental component scores (MCS) at Week 12 (Asia Cohort)

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End point title

Change from Baseline in SF-36 mental component scores (MCS) at Week 12 (Asia Cohort) ^[178]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[178] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	42	19	21
Units: T-Score
arithmetic mean (standard deviation)	1.529 ± 9.2379	2.197 ± 8.4871	1.149 ± 7.6184	0.392 ± 7.0528

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 domain scores at Week 12 (Asia Cohort)

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End point title

Change from Baseline in SF-36 domain scores at Week 12 (Asia Cohort) ^[179]

End point description

SF-36 survey assessed health-related quality of life, covering physical functioning, bodily pain, role limitations due to physical/emotional issues, general health, mental health, social functioning, and vitality. MCS consists of four domains (MH, vitality, SF, role-emotional), and PCS consists of four domains (PF, role-physical, BP, GH).Individual question items were totaled within items under various sections, and these domain scores were then scaled from 0 to 100, with higher scores indicating better health. Positive changes from the baseline indicated improvements. Scoring of SF-36 utilized Quality Metric software. Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits. CB=subtracting PD visit value from BV. For analysis up to week 12, placebo arms were pooled into single arm to serve as reference for active treatment arm comparison. Analysis was performed on ITT-Supplementary Asia Cohort set with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[179] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	42	19	21
Units: Scores on a scale
arithmetic mean (standard deviation)
Bodily Pain, n=45,42,19,21	12.64 ± 13.888	7.93 ± 14.984	23.42 ± 22.741	1.62 ± 18.712
General Health, n=45,42,19,21	6.33 ± 17.092	2.86 ± 13.448	9.16 ± 15.174	-4.05 ± 14.928
Mental Health, n=45,42,19,21	4.00 ± 17.340	1.43 ± 14.579	1.32 ± 14.419	0.24 ± 13.179
Physical Function, n=45,42,19,21	8.67 ± 15.537	8.10 ± 17.355	14.74 ± 19.037	1.90 ± 18.740
Role Emotional, n=45,42,19,21	5.93 ± 20.150	7.54 ± 23.268	7.89 ± 21.957	2.38 ± 25.020
Role Physical, n=45,42,19,21	8.89 ± 16.722	8.33 ± 23.494	20.07 ± 30.730	2.98 ± 19.924
Social Function, n=45,42,19,21	3.06 ± 20.670	8.63 ± 20.379	13.82 ± 19.937	0.00 ± 16.298
Vitality, n=45,42,19,21	7.22 ± 20.684	8.48 ± 15.849	9.54 ± 20.023	2.08 ± 11.238

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[180]

End point description

SF-36 survey evaluates health-related quality of life, covering physical functioning(PF), bodily pain(BP), role limitations due to physical/emotional issues, general health(GH), MH, SF, vitality. Each domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains(PF, role-physical, BP, GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[180] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	37	42	17
Units: T-Score
arithmetic mean (standard deviation)
Week 24, n=37,42,17	4.220 ± 7.5564	3.362 ± 5.9357	7.826 ± 9.0545
Week 52, n=31,31,15	4.646 ± 6.7378	5.328 ± 5.8824	9.942 ± 5.7938

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[181]

End point description

SF-36 survey evaluates health-related quality of life, covering physical functioning, bodily pain, role limitations due to physical/emotional issues, general health, mental health(MH), social functioning(SF), vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains(SF, MH, vitality, role-emotional) representing overall mental health. Positive change from baseline, reported using T-score change, indicates improvement in overall mental health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[181] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	37	42	17
Units: T-Score
arithmetic mean (standard deviation)
Week 24, n=37,42,17	-0.157 ± 8.7537	2.741 ± 6.6865	0.071 ± 8.0170
Week 52, n=31,31,15	3.837 ± 9.6474	0.918 ± 10.3466	1.923 ± 9.4063

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

Top of page

End point title

Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[182]

End point description

SF-36 survey assessed health-related quality of life, covering physical functioning, bodily pain, role limitations due to physical/emotional issues, general health, mental health, social functioning, and vitality. MCS consists of four domains (MH,vitality,SF,role-emotional), and PCS consists of four domains (PF,role-physical,BP,GH).Individual question items were totaled within items under various sections, and these domain scores were then scaled from 0 to 100, with higher scores indicating better health. Positive changes from the baseline indicated improvements. Scoring of SF-36 utilized Quality Metric software. Baseline was defined as most recent pre-dose non-missing value, including unscheduled visits. Change from baseline was calculated by subtracting post dose value from Baseline value. Participants who received study intervention from Day 1 to Week 52 in Asia Cohort with data available at indicated timepoints were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[182] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	37	42	17
Units: Scores on a scale
arithmetic mean (standard deviation)
Bodily Pain, Week 24, n=37,42,17	13.43 ± 18.292	8.88 ± 13.862	30.59 ± 25.048
Bodily Pain, Week 52, n=31,31,15	16.77 ± 17.333	16.97 ± 16.956	30.20 ± 23.035
General Health, Week 24, n=37,42,17	4.97 ± 19.591	4.19 ± 14.101	2.41 ± 12.037
General Health, Week 52, n=31,31,15	5.74 ± 17.216	4.13 ± 14.509	10.87 ± 13.958
Mental Health, Week 24, n=37,42,17	0.68 ± 18.226	4.17 ± 13.521	2.65 ± 9.701
Mental Health, Week 52, n=31,31,15	7.42 ± 18.343	1.29 ± 17.510	6.00 ± 17.341
Physical Function, Week 24, n=37,42,17	6.08 ± 18.264	10.60 ± 17.916	14.71 ± 20.269
Physical Function, Week 52, n=31,31,15	10.00 ± 17.512	11.29 ± 17.367	21.67 ± 17.491
Role Emotional, Week 24, n=37,42,17	1.58 ± 22.209	8.53 ± 19.259	9.80 ± 25.215
Role Emotional, Week 52, n=31,31,15	9.41 ± 20.609	8.87 ± 23.267	11.11 ± 21.973
Role Physical, Week 24, n=37,42,17	8.45 ± 24.572	8.63 ± 20.332	18.01 ± 40.437
Role Physical, Week 52, n=31,31,15	13.31 ± 18.381	12.90 ± 23.768	21.67 ± 30.969
Social Function, Week 24, n=37,42,17	2.70 ± 18.194	8.63 ± 16.904	3.68 ± 37.699
Social Function, Week 52, n=31,31,15	10.48 ± 20.941	5.24 ± 22.770	11.67 ± 28.530
Vitality, Week 24, n=37,42,17	5.07 ± 22.040	8.04 ± 15.937	4.78 ± 25.342
Vitality, Week 52, n=31,31,15	11.49 ± 22.308	6.05 ± 21.377	11.25 ± 23.170

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[183]

End point description

SF-36 survey evaluates health-related quality of life, covering physical functioning(PF), bodily pain(BP), role limitations due to physical/emotional issues, general health(GH), MH, SF, vitality. Each domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains(PF, role-physical, BP, GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data. For efficacy assessments baseline is interpreted as Day 1.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[183] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: T-Score
arithmetic mean (standard deviation)
Week 24, n=6,6,7	1.762 ± 5.8183	1.675 ± 6.9009	5.544 ± 5.4800
Week 52, n=4,6,7	3.818 ± 3.4904	3.268 ± 4.8182	7.024 ± 6.0185

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[184]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[184] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: T-Score
arithmetic mean (standard deviation)
Week 24, n=6,6,7	3.158 ± 8.1659	3.950 ± 5.3971	4.889 ± 8.1905
Week 52, n=4,6,7	-0.028 ± 9.4600	-1.940 ± 8.3373	2.401 ± 6.1426

No statistical analyses for this end point

Secondary: Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[185]

End point description

SF-36 is a health-related survey that assesses quality of life covering 8 domains: physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health(MH),social functioning(SF),vitality. The MCS consists of 4 domains (SF,MH,vitality,role-emotional) and PCS consists of 4 domains (PF,role-physical,BP,GH). The individual question items are first summed, then domain scores are weighted to a scale between 0 to 100, where higher score represents better health. Positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline value. For efficacy assessments baseline is interpreted as Day 1. ITT set was analyzed for participants with data available at the indicated time points.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[185] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Scores on a scale
arithmetic mean (standard deviation)
Bodily Pain, Week 24, n=6,6,7	18.83 ± 23.017	12.17 ± 26.180	18.00 ± 23.951
Bodily Pain, Week 52, n=4,6,7	13.50 ± 26.889	12.83 ± 37.280	23.00 ± 20.905
General Health, Week 24, n=6,6,7	-3.83 ± 14.689	0.83 ± 16.558	-1.29 ± 12.148
General Health, Week 52, n=4,6,7	5.00 ± 14.697	-0.83 ± 13.934	0.57 ± 18.911
Mental Health, Week 24, n=6,6,7	9.17 ± 13.197	5.83 ± 12.813	14.29 ± 5.345
Mental Health, Week 52, n=4,6,7	1.25 ± 13.769	-2.50 ± 16.355	6.43 ± 7.480
Physical Function, Week 24, n=6,6,7	0.01 ± 17.887	2.50 ± 15.732	25.71 ± 18.356
Physical Function, Week 52, n=4,6,7	2.51 ± 18.925	5.83 ± 10.205	21.43 ± 15.738
Role Emotional, Week 24, n=6,6,7	11.11 ± 24.532	9.72 ± 16.171	15.48 ± 40.379
Role Emotional, Week 52, n=4,6,7	0.00 ± 11.785	-2.78 ± 21.515	11.91 ± 27.154
Role Physical, Week 24, n=6,6,7	13.54 ± 15.520	7.29 ± 10.013	15.18 ± 21.907
Role Physical, Week 52, n=4,6,7	9.38 ± 14.878	1.04 ± 14.479	16.96 ± 25.697
Social Function, Week 24, n=6,6,7	-2.08 ± 20.026	4.17 ± 6.455	3.57 ± 17.252
Social Function, Week 52, n=4,6,7	3.13 ± 31.250	-6.25 ± 15.309	10.71 ± 18.298
Vitality, Week 24, n=6,6,7	3.13 ± 11.693	11.46 ± 14.479	15.18 ± 8.733
Vitality, Week 52, n=4,6,7	4.69 ± 23.593	8.33 ± 6.455	8.93 ± 14.815

No statistical analyses for this end point

Secondary: Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12 (Asia Cohort)

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End point title

Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12 (Asia Cohort) ^[186]

End point description

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on ITT-Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[186] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	46	42	19	21
Units: Scores on a scale
arithmetic mean (standard deviation)	2.4 ± 8.01	4.0 ± 6.58	6.4 ± 7.64	0.3 ± 9.00

No statistical analyses for this end point

Secondary: Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[187]

End point description

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. The analysis was performed on all randomized Asia Cohort participants who received study intervention from Day 01 to Week 52. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[187] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	42	17
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=38,42,17	1.9 ± 9.22	4.7 ± 5.96	5.1 ± 10.18
Week 52, n=32,31,15	3.3 ± 8.91	5.3 ± 7.65	7.7 ± 8.91

No statistical analyses for this end point

Secondary: Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[188]

End point description

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For efficacy assessments baseline is interpreted as Day 1. The analysis was performed on all randomized Asia Cohort participants who switched from placebo to study intervention at Week 12. Participants with data available at indicated timepoints are analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[188] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=6,6,7	6.3 ± 5.16	1.3 ± 4.93	3.0 ± 10.17
Week 52, n=4,6,7	4.0 ± 6.16	2.2 ± 1.94	2.0 ± 7.94

No statistical analyses for this end point

Secondary: Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) (Asia Cohort)

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End point title

Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) (Asia Cohort) ^[189]

End point description

AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with use of a study intervention, whether or not considered related to study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs were included. The analysis was performed on Safety Set that includes all randomized participants who received at least one dose of study treatment. Pooled Placebo collected data from Day 01 to Week 12. Placebo switched arms collected data from Week 12 to 59. Experimental arms collected data from Day 01 to Week 59.

End point type

Secondary

End point timeframe

Up to Week 59

Notes
[189] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: <The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	47	49	19	23
Units: Participants
AE	37	43	18	14
SAE	5	4	2	1
AESI	4	6	2	0

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of white blood cell (WBC) count, platelet count, neutrophils, lymphocytes at Week 12 (Giga cells per liter) (Asia Cohort)

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End point title

Change from Baseline in hematology parameter of white blood cell (WBC) count, platelet count, neutrophils, lymphocytes at Week 12 (Giga cells per liter) (Asia Cohort) ^[190]

End point description

Blood samples were collected for the assessment of change from baseline in hematology parameters including WBC count, platelet count, neutrophils, lymphocytes. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[190] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	43	19	21
Units: Giga cells per liter (10^9/L)
arithmetic mean (standard deviation)
WBC count, n=45,43,19,21	-0.48 ± 1.369	-0.35 ± 1.699	-1.25 ± 1.038	-0.18 ± 1.518
Platelet count, n=45,43,19,21	-17.8 ± 51.99	-20.4 ± 44.57	-22.9 ± 50.17	5.7 ± 48.47
Neutrophils, n=45,43,19,21	-0.654 ± 1.3274	-0.473 ± 1.5847	-1.316 ± 1.0213	-0.352 ± 1.2533
Lymphocytes, n=45,43,19,21	0.094 ± 0.3241	0.069 ± 0.3391	0.070 ± 0.4069	0.117 ± 0.4069

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of WBC count, platelet count, neutrophils, lymphocytes at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

Top of page

End point title

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[191] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Giga cells per liter (10^9/L)
arithmetic mean (standard deviation)
WBC count, Week 24, n=38,43,17	-0.42 ± 1.780	-0.56 ± 1.467	-0.26 ± 3.492
WBC count, Week 52, n=29,28,16	-0.60 ± 1.538	-0.50 ± 1.338	-1.30 ± 1.207
Platelet count, Week 24, n=38,43,17	-24.8 ± 61.57	-8.0 ± 39.63	-3.2 ± 74.58
Platelet count, Week 52, n=29,28,16	-27.4 ± 54.86	-24.5 ± 53.19	-28.6 ± 51.39
Neutrophils, Week 24, n=38,43,17	-0.632 ± 1.7911	-0.737 ± 1.3842	-0.829 ± 1.7091
Neutrophils, Week 52, n=29,28,16	-0.794 ± 1.6493	-0.475 ± 1.1881	-0.828 ± 1.2338
Lymphocytes, Week 24, n=38,43,17	0.107 ± 0.3436	0.114 ± 0.2605	0.454 ± 1.7675
Lymphocytes, Week 52, n=29,28,16	0.129 ± 0.3706	-0.002 ± 0.2894	-0.414 ± 0.3126

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of WBC count, platelet count, neutrophils, lymphocytes at Week 24 and Week 52 (Asia Cohort)

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End point title

Change from Baseline in hematology parameter of WBC count, platelet count, neutrophils, lymphocytes at Week 24 and Week 52 (Asia Cohort) ^[192]

End point description

Blood samples were collected for the assessment of change from baseline in hematology parameters including WBC count, platelet count, neutrophils, lymphocytes. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on Safety Set participants who switched from placebo to study intervention at Week 12. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[192] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Giga cells per liter (10^9/L)
arithmetic mean (standard deviation)
WBC count, Week 24, n=6,6,7	-0.10 ± 1.404	-1.10 ± 0.729	-0.53 ± 1.559
WBC count, Week 52, n=4,5,6	-0.28 ± 0.544	-0.08 ± 1.057	0.85 ± 1.285
Platelet count, Week 24, n=6,6,7	-33.5 ± 39.29	1.2 ± 45.66	-54.4 ± 72.52
Platelet count, Week 52, n=4,5,6	-33.8 ± 48.88	-27.4 ± 49.23	-62.7 ± 67.67
Neutrophils, Week 24, n=6,6,7	0.042 ± 1.1970	-1.153 ± 0.8378	-0.599 ± 1.6470
Neutrophils, Week 52, n=4,5,6	-0.205 ± 0.3770	-0.040 ± 0.6118	1.305 ± 1.0918
Lymphocytes, Week 24, n=6,6,7	-0.160 ± 0.2929	0.185 ± 0.3747	0.030 ± 0.4946
Lymphocytes, Week 52, n=4,5,6	0.093 ± 0.1962	0.092 ± 0.3667	-0.568 ± 0.5136

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of hemoglobin at Week 12 (Asia Cohort)

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End point title

Change from Baseline in hematology parameter of hemoglobin at Week 12 (Asia Cohort) ^[193]

End point description

Blood samples was collected for the assessment of hematology parameters. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[193] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study._

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	45	43	19	21
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)	2.3 ± 8.44	0.0 ± 8.45	1.4 ± 5.70	-1.7 ± 7.31

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[194]

End point description

Blood samples was collected for the assessment of hematology parameters. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. The analysis was performed on Safety Set participants who received study intervention from Day 01 to Week 52. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[194] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Week 24, n=38,43,17	3.2 ± 10.72	-0.8 ± 9.81	2.4 ± 8.97
Week 52, n=29,28,15	1.9 ± 10.65	-1.8 ± 9.95	2.4 ± 9.76

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), Gamma-Glutamyl transpeptidase (GGT) at Week 12 (Asia Cohort)

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End point title

End point description

Blood samples were collected for the assessment of clinical chemistry parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) and gamma-glutamyl transferase (GGT) levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[195] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	46	43	19	21
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
Aspartate Aminotransferase	3.5 ± 13.14	2.0 ± 5.29	2.9 ± 4.82	0.8 ± 8.26
Alanine Aminotransferase	2.1 ± 16.90	2.5 ± 7.49	0.0 ± 7.85	2.8 ± 16.44
Alkaline Phosphatase	-1.9 ± 14.73	-1.0 ± 11.52	-4.2 ± 15.44	-0.6 ± 16.52
Gamma-Glutamyl Transpeptidase	-3.0 ± 10.95	0.7 ± 12.28	-3.5 ± 14.69	2.6 ± 12.52

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[196]

End point description

Blood samples was collected for the assessment of hematology parameters. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on Safety Set participants who switched from placebo to study intervention at Week 12. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[196] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Week 24, n=6,6,7	-0.5 ± 7.94	-1.2 ± 8.77	3.3 ± 4.68
Week 52, n=4,5,6	-0.5 ± 6.35	-1.0 ± 11.51	2.5 ± 7.23

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[197]

End point description

Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on Safety Set participants who received study intervention from Day 01 to Week 52. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[197] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
AST. Week 24, n=38,43,17	0.1 ± 10.02	2.1 ± 6.20	3.2 ± 7.27
AST. Week 52, n=29,28,16	0.9 ± 8.65	1.2 ± 5.34	4.2 ± 10.58
ALT, Week 24, n=38,43,17	-1.0 ± 16.19	2.5 ± 8.56	-0.2 ± 4.22
ALT, Week 52, n=29,28,16	-2.3 ± 15.36	-0.4 ± 5.95	2.0 ± 19.78
AP, Week 24, n=38,43,17	-0.3 ± 15.15	0.3 ± 16.64	-5.6 ± 15.14
AP, Week 52, n=29,28,16	-5.7 ± 15.00	-6.3 ± 18.37	-5.1 ± 21.76
GGT, Week 24, n=38,43,17	-4.4 ± 9.83	0.7 ± 16.68	-5.0 ± 17.60
GGT, Week 52, n=29,28,16	-6.8 ± 10.38	-2.1 ± 12.53	1.4 ± 20.96

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[198]

End point description

Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on Safety Set participants who switched from placebo to study intervention at Week 12. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[198] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
AST, Week 24, n=6,6,7	-0.5 ± 2.43	-4.0 ± 9.14	4.3 ± 4.07
AST, Week 52, n=4,5,6	1.3 ± 2.36	-1.2 ± 1.64	2.6 ± 5.41
ALT, Week 24, n=6,6,7	0.5 ± 2.43	-14.0 ± 25.91	1.7 ± 7.36
ALT, Week 52, n=4,5,6	6.0 ± 6.98	-4.0 ± 5.92	-2.0 ± 8.75
AP, Week 24, n=6,6,7	-0.3 ± 7.74	-6.0 ± 12.57	0.0 ± 26.44
AP, Week 52, n=4,5,6	-10.5 ± 18.16	1.6 ± 4.98	-13.6 ± 21.48
GGT, Week 24, n=6,6,7	-1.3 ± 5.75	-10.8 ± 23.23	-6.0 ± 12.94
GGT, Week 52, n=4,5,6	3.0 ± 6.78	-4.0 ± 12.53	-7.6 ± 15.45

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of total bilirubin at Week 12 (Asia Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 12 (Asia Cohort) ^[199]

End point description

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[199] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: <The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	46	43	19	21
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)	0.2 ± 2.32	0.1 ± 2.64	1.1 ± 4.71	-0.1 ± 2.68

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[200]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[200] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)
Week 24, n=38,43,17	0.3 ± 2.60	0.2 ± 2.82	0.3 ± 2.79
Week 52, n=29,28,16	0.7 ± 2.69	1.6 ± 4.75	1.6 ± 2.85

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[201]

End point description

Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on Safety Set participants who switched from placebo to study intervention at Week 12. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[201] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)
Week 24, n=6,6,7	-0.7 ± 1.97	3.2 ± 3.54	0.3 ± 2.75
Week 52, n=4,5,5	0.0 ± 1.41	22.0 ± 2.00	0.0 ± 1.41

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[202]

End point description

Blood samples was collected for the assessment of clinical chemistry parameter albumin. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. The analysis was performed on Safety Set participants who received study intervention from Day 01 to Week 52. Only those participants with data available at the indicated timepoints were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1), Week 24 and Week 52

Notes
[202] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	38	43	17
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Week 24, n=38,43,17	0.8 ± 2.81	0.3 ± 2.90	1.4 ± 4.01
Week 52, n=29,28,16	1.0 ± 2.54	0.2 ± 2.47	2.6 ± 3.50

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of albumin at Week 12 (Asian Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of albumin at Week 12 (Asian Cohort) ^[203]

End point description

Blood samples was collected for the assessment of clinical chemistry parameter albumin. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[203] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	46	43	19	21
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)	0.8 ± 2.99	-0.2 ± 2.26	2.1 ± 2.51	-0.5 ± 2.68

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for placebo switched arms (Asia Cohort) ^[204]

End point description

Blood samples was collected for the assessment of clinical chemistry parameter albumin. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on Safety Set participants who switched from placebo to study intervention at Week 12. Only those participants with data available at the indicated timepoints were analyzed.

End point type

Secondary

End point timeframe

Baseline (Week 12), Week 24 and Week 52

Notes
[204] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	6	7
Units: Grams per liter (g/L)
arithmetic mean (standard deviation)
Week 24, n=6,6,7	0.3 ± 3.01	1.2 ± 1.83	2.1 ± 2.54
Week 52, n=4,5,5	0.3 ± 1.71	2.0 ± 1.58	3.8 ± 3.70

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 12 (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 12 (Asia Cohort) ^[205]

End point description

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Blood samples were collected at indicated time points as per schedule of assessment in the protocol. The Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for the lipid panel, there is no corresponding time point in the schedule of assessment. Consequently, the only objective that can be assessed for the lipid panel is Week 4 and not at Week 12.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[205] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	0 ^[206]	0 ^[207]	0 ^[208]	0 ^[209]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±	±

Notes
[206] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[207] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[208] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[209] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[210]

End point description

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24

Notes
[210] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	0 ^[211]	0 ^[212]	0 ^[213]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[211] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[212] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[213] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for placebo switched arms (Asia Cohort) ^[214]

End point description

Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Week 12) and Week 24

Notes
[214] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	0 ^[215]	0 ^[216]	0 ^[217]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[215] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[216] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[217] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[218]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 52

Notes
[218] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	29	29	16
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	-0.166 ± 0.8128	0.146 ± 0.5227	0.743 ± 0.7569

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for placebo switched arms (Asia Cohort) ^[219]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 4) and Week 52

Notes
[219] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	4	5	5
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	0.085 ± 0.4905	0.318 ± 1.4969	0.816 ± 0.5924

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol at Week 12 (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol at Week 12 (Asia Cohort) ^[220]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[220] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	0 ^[221]	0 ^[222]	0 ^[223]	0 ^[224]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±	±

Notes
[221] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[222] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[223] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[224] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for placebo switched arms (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for placebo switched arms (Asia Cohort) ^[225]

End point description

Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Week 12) and Week 24

Notes
[225] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	0 ^[226]	0 ^[227]	0 ^[228]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[226] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[227] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[228] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[229]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24

Notes
[229] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	0 ^[230]	0 ^[231]	0 ^[232]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[230] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[231] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[232] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for placebo switched arms (Asia Cohort) ^[233]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 4) and Week 52

Notes
[233] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	4	5	5
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
LDL Cholesterol, n=4,5,5	0.218 ± 0.5604	0.094 ± 1.2936	0.438 ± 0.4544
HDL Cholesterol, n=4,5,5,	0.000 ± 0.1089	0.042 ± 0.2400	0.226 ± 0.2204

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[234]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 52

Notes
[234] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	29	29	16
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
LDL Cholesterol, n=28,29,16	-0.258 ± 0.7697	0.076 ± 0.4614	0.334 ± 0.4170
HDL Cholesterol, n=29,29,16	-0.044 ± 0.2490	-0.012 ± 0.2779	0.146 ± 0.3082

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 12 (Asia Cohort)

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End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 12 (Asia Cohort) ^[235]

End point description

Blood samples was collected for the assessment of fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 4 and not Week 12 as no data collected. Week 4 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 12

Notes
[235] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	0 ^[236]	0 ^[237]	0 ^[238]	0 ^[239]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±	±

Notes
[236] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[237] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[238] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[239] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort)

Top of page

End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 52 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[240]

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 52

Notes
[240] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	29	29	16
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	0.443 ± 1.4807	0.180 ± 0.4439	0.345 ± 0.6262

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 24 for placebo switched arms (Asia Cohort)

Top of page

End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 24 for placebo switched arms (Asia Cohort) ^[241]

End point description

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Week 12) and Week 24

Notes
[241] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	0 ^[242]	0 ^[243]	0 ^[244]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[242] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[243] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[244] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 24 for treatment arms who started study intervention from Day 1 (Asia Cohort)

Top of page

End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 24 for treatment arms who started study intervention from Day 1 (Asia Cohort) ^[245]

End point description

Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24

Notes
[245] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	0 ^[246]	0 ^[247]	0 ^[248]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	±	±	±

Notes
[246] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[247] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
[248] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.

No statistical analyses for this end point

Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 52 for placebo switched arms (Asia Cohort)

Top of page

End point title

Change from Baseline in lipid profile parameter of triglycerides at Week 52 for placebo switched arms (Asia Cohort) ^[249]

End point description

End point type

Secondary

End point timeframe

Baseline (Week 4) and Week 52

Notes
[249] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	4	5	5
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)	-0.288 ± 0.7348	0.398 ± 0.6266	0.328 ± 0.5965

No statistical analyses for this end point

Secondary: Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities (Asia Cohort)

Top of page

End point title

Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities (Asia Cohort) ^[250]

End point description

Number of participants with NCI-CTCAE >=Grade 3 hematological/clinical chemistry abnormalities were summarized. Hematological and Clinical chemistry parameters were summarized according to the NCI-CTCAE, version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Data is presented for only those parameters for which participants had worst case >=Grade 3 shifts from Baseline. The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study treatment. Pooled Placebo collected data till Week 12. Placebo switched arms collected data from Week 12 to 59. Experimental arm collected data from Day 01 to Week 59.

End point type

Secondary

End point timeframe

Up to Week 59

Notes
[250] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)	Pooled Placebo (Asia Cohort)
Number of subjects analysed	47	49	19	6	8	8	23
Units: Participants
Cholesterol - high, Total, Grade 3	1	0	0	0	0	0	0
Lymphocyte count decreased, Total, Grade 3	1	1	2	0	0	0	0
Hypertriglyceridemia, Total, Grade 3	1	1	1	0	0	0	0

No statistical analyses for this end point

Secondary: Concentrations of Granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody (Asia Cohort)

Top of page

End point title

Concentrations of Granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody (Asia Cohort) ^[251]

End point description

Blood samples were collected for markers which may influence rheumatoid arthritis. Concentrations of GM-CSF autoantibodies was determined. The analysis was performed on the Safety Set. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

At baseline

Notes
[251] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	1 ^[252]	0 ^[253]	0 ^[254]	0 ^[255]	0 ^[256]	0 ^[257]
Units: Microgram per liter (ug/L)
arithmetic mean (standard deviation)	526.0 ± 0	±	±	±	±	±

Notes
[252] - Standard Deviation was not derived as only one participant was analyzed.
[253] - No participants were analyzed at the timepoint.
[254] - No participants were analyzed at the timepoint.
[255] - No participants were analyzed at the timepoint.
[256] - No participants were analyzed at the timepoint.
[257] - No participants were analyzed at the timepoint.

No statistical analyses for this end point

Secondary: Number of participants with anti-GSK3196165 antibodies (Asia Cohort)

Top of page

End point title

Number of participants with anti-GSK3196165 antibodies (Asia Cohort) ^[258]

End point description

Serum samples were collected for the determination of anti- GSK3196165 antibodies (ADA) using a validated electrochemiluminescence (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Additionally, confirmed positive ADA samples were also tested in a validated neutralizing antibody assay to determine the potential neutralizing activity of the ADA.

End point type

Secondary

End point timeframe

Up to Week 59

Notes
[258] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	GSK3196165 90mg + csDMARD (Asia Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	47	49	19	6	8	9
Units: Participants	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) for placebo switched arms (Global Cohort)

Top of page

End point title

Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) for placebo switched arms (Global Cohort) ^[259]

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death. The analysis was performed on Safety Set of switched arms that collected data from Week 12 to 59.

End point type

Secondary

End point timeframe

Week 12 to Week 59

Notes
[259] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	85	80	67
Units: Participants
Participants with AE	54	52	45
Participants with SAE	5	3	2
Participants with AESI	6	12	3

No statistical analyses for this end point

Secondary: Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities for placebo switched arms (Global Cohort)

Top of page

End point title

Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities for placebo switched arms (Global Cohort) ^[260]

End point description

End point type

Secondary

End point timeframe

Week 12 to Week 59

Notes
[260] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
Number of subjects analysed	85	80	67
Units: Participants
Anemia, Total, Grade 3	0	2	1
Lymphocyte count decreased, Grade 3	1	0	2
Neutrophil count decreased, Total, Grade 3	0	1	0
Lymphocyte count decreased, Grade 4	0	0	1
Hypertriglyceridemia, Total, Grade 3	0	1	0

No statistical analyses for this end point

Secondary: Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) for placebo switched arms (Asia Cohort)

Top of page

End point title

Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) for placebo switched arms (Asia Cohort) ^[261]

End point description

End point type

Secondary

End point timeframe

Week 12 to Week 59

Notes
[261] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	8	8
Units: Participants
Participants with AE	6	5	7
Participants with SAE	0	1	0
Participants with AESI	0	0	0

No statistical analyses for this end point

Secondary: Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities for placebo switched arms (Asia Cohort)

Top of page

End point title

End point description

End point type

Secondary

End point timeframe

Week 12 to Week 59

Notes
[262] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoints are different for the different parts of the study.

End point values	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Number of subjects analysed	6	8	8
Units: Participants
Cholesterol - high, Total, Grade 3	0	0	0
Lymphocyte count decreased, Total, Grade 3	0	0	0
Hypertriglyceridemia, Total, Grade 3	0	0	0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

For Global and Asia cohorts, Pooled Placebo arm collected during the timeframe Week 0 to Week 12. Placebo switched to active treatment arms collected during the timeframe Week 12 to Week 59. Experimental arms collected during from Week 0 to Week 59.

Adverse event reporting additional description

Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis.

Assessment type

Systematic

Dictionary name

v25.0

Dictionary version

25.0

Reporting group title

GSK3196165 90mg + csDMARD (Global Cohort)

Reporting group description

Reporting group title

GSK3196165 150mg + csDMARD (Global Cohort)

Reporting group description

Participants in Global Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Reporting group title

Tofacitinib 5mg + csDMARD (Global Cohort)

Reporting group description

Participants in Global Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Reporting group title

GSK3196165 150mg + csDMARD (Asia Cohort)

Reporting group description

Participants in Asia Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Reporting group title

Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)

Reporting group description

Reporting group title

Pooled Placebo (Global Cohort)

Reporting group description

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12. The placebo arms are pooled into a single placebo arm.

Reporting group title

Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)

Reporting group description

Reporting group title

Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)

Reporting group description

Reporting group title

GSK3196165 90mg + csDMARD (Asia Cohort)

Reporting group description

Participants in Asia Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Reporting group title

Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)

Reporting group description

Reporting group title

Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)

Reporting group description

Reporting group title

Pooled Placebo (Asian Cohort)

Reporting group description

Participants received Placebo weekly SC injection in combination with csDMARD until Week 12. The placebo arms are pooled into a single placebo arm.

Reporting group title

Tofacitinib 5mg + csDMARD (Asia Cohort)

Reporting group description

Participants in Asia Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

Reporting group title

Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)

Reporting group description

GSK3196165 90mg + csDMARD (Global Cohort)

GSK3196165 150mg + csDMARD (Global Cohort)

Tofacitinib 5mg + csDMARD (Global Cohort)

GSK3196165 150mg + csDMARD (Asia Cohort)

Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)

Pooled Placebo (Global Cohort)

Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)

Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)

GSK3196165 90mg + csDMARD (Asia Cohort)

Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)

Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)

Pooled Placebo (Asian Cohort)

Tofacitinib 5mg + csDMARD (Asia Cohort)

Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)

Total subjects affected by serious adverse events

subjects affected / exposed

44 / 545 (8.07%)

43 / 539 (7.98%)

31 / 286 (10.84%)

4 / 49 (8.16%)

2 / 67 (2.99%)

6 / 255 (2.35%)

5 / 85 (5.88%)

3 / 80 (3.75%)

5 / 47 (10.64%)

1 / 8 (12.50%)

0 / 6 (0.00%)

1 / 23 (4.35%)

2 / 19 (10.53%)

0 / 8 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma of colon

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Breast cancer

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac myxoma

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chronic lymphocytic leukaemia

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colorectal adenoma

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

1 / 255 (0.39%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastric cancer

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Invasive ductal breast carcinoma

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Invasive lobular breast carcinoma

subjects affected / exposed

0 / 545 (0.00%)

2 / 539 (0.37%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Lung neoplasm

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Metastases to liver

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatic carcinoma metastatic

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rectal adenocarcinoma

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transitional cell carcinoma

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

1 / 80 (1.25%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Uterine leiomyoma

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

1 / 47 (2.13%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Circulatory collapse

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

1 / 85 (1.18%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Deep vein thrombosis

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Death

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Fatigue

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sudden death

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Immune system disorders

Secondary amyloidosis

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

Endometrial hyperplasia

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hydrosalpinx

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Menopausal symptoms

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ovarian cyst

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Uterine polyp

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endometriosis

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

1 / 47 (2.13%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Uterine cyst

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

1 / 47 (2.13%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

1 / 49 (2.04%)

0 / 67 (0.00%)

0 / 255 (0.00%)

1 / 85 (1.18%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural cyst

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

1 / 80 (1.25%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 545 (0.00%)

2 / 539 (0.37%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary fibrosis

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Product issues

Device dislocation

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

1 / 255 (0.39%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

International normalised ratio increased

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transaminases increased

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

1 / 255 (0.39%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Incisional hernia

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ankle fracture

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Joint injury

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Overdose

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Skin laceration

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal compression fracture

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

1 / 286 (0.35%)

1 / 49 (2.04%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tendon rupture

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tibia fracture

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wound dehiscence

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

Developmental hip dysplasia

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

1 / 47 (2.13%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed

2 / 545 (0.37%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Angina unstable

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

1 / 545 (0.18%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac arrest

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

1 / 80 (1.25%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Myocardial infarction

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pericardial effusion

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sinus node dysfunction

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Cerebral infarction

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

1 / 23 (4.35%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebrovascular accident

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Facial paralysis

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ischaemic stroke

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Paraparesis

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subarachnoid haemorrhage

subjects affected / exposed

1 / 545 (0.18%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Syncope

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transient ischaemic attack

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

1 / 85 (1.18%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lacunar infarction

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

1 / 47 (2.13%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

1 / 85 (1.18%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Iron deficiency anaemia

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenia

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

1 / 49 (2.04%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

Glaucoma

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ulcerative keratitis

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Duodenal ulcer

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

1 / 85 (1.18%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Acute abdomen

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Duodenal ulcer perforation

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enteritis

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastric ulcer

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Inguinal hernia

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Large intestine polyp

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

1 / 67 (1.49%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mesenteric cyst

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peritoneal adhesions

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Acute hepatic failure

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Bile duct stone

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholecystitis acute

subjects affected / exposed

2 / 545 (0.37%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cholelithiasis

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic steatosis

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Calculus urinary

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

IgA nephropathy

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intervertebral disc degeneration

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Joint destruction

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lumbar spinal stenosis

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Osteoarthritis

subjects affected / exposed

4 / 545 (0.73%)

4 / 539 (0.74%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

1 / 255 (0.39%)

0 / 85 (0.00%)

1 / 80 (1.25%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 4

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Osteoporotic fracture

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rheumatoid arthritis

subjects affected / exposed

1 / 545 (0.18%)

2 / 539 (0.37%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

2 / 85 (2.35%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 2

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal osteoarthritis

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Synovial cyst

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Synovitis

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

1 / 255 (0.39%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tenosynovitis

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Soft tissue disorder

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

1 / 49 (2.04%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

COVID-19

subjects affected / exposed

1 / 545 (0.18%)

2 / 539 (0.37%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

1 / 47 (2.13%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

1 / 19 (5.26%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Appendicitis

subjects affected / exposed

0 / 545 (0.00%)

2 / 539 (0.37%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

COVID-19 pneumonia

subjects affected / exposed

5 / 545 (0.92%)

5 / 539 (0.93%)

7 / 286 (2.45%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 5

0 / 7

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 2

0 / 1

0 / 0

Diverticulitis

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia sepsis

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes simplex

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes zoster

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower respiratory tract infection

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

1 / 67 (1.49%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumocystis jirovecii pneumonia

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

2 / 545 (0.37%)

1 / 539 (0.19%)

2 / 286 (0.70%)

1 / 49 (2.04%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

1 / 80 (1.25%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 2

1 / 1

0 / 2

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia bacterial

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Postoperative wound infection

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

1 / 85 (1.18%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Post procedural infection

subjects affected / exposed

0 / 545 (0.00%)

1 / 539 (0.19%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis acute

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

1 / 47 (2.13%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Septic shock

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

1 / 286 (0.35%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

1 / 255 (0.39%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia cryptococcal

subjects affected / exposed

0 / 545 (0.00%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

1 / 19 (5.26%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

1 / 545 (0.18%)

0 / 539 (0.00%)

0 / 286 (0.00%)

0 / 49 (0.00%)

0 / 67 (0.00%)

0 / 255 (0.00%)

0 / 85 (0.00%)

0 / 80 (0.00%)

0 / 47 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 23 (0.00%)

0 / 19 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	GSK3196165 90mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Global Cohort)	Tofacitinib 5mg + csDMARD (Global Cohort)	GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)	Pooled Placebo (Global Cohort)	Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)	Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)	GSK3196165 90mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)	Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)	Pooled Placebo (Asian Cohort)	Tofacitinib 5mg + csDMARD (Asia Cohort)	Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
Total subjects affected by non serious adverse events
subjects affected / exposed	233 / 545 (42.75%)	208 / 539 (38.59%)	105 / 286 (36.71%)	39 / 49 (79.59%)	23 / 67 (34.33%)	3 / 255 (1.18%)	28 / 85 (32.94%)	31 / 80 (38.75%)	28 / 47 (59.57%)	5 / 8 (62.50%)	6 / 6 (100.00%)	10 / 23 (43.48%)	18 / 19 (94.74%)	7 / 8 (87.50%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Uterine leiomyoma
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Vascular disorders
Hypertension
subjects affected / exposed	30 / 545 (5.50%)	31 / 539 (5.75%)	19 / 286 (6.64%)	5 / 49 (10.20%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	2 / 23 (8.70%)	1 / 19 (5.26%)	1 / 8 (12.50%)
occurrences all number	32	32	20	5	0	0	0	0	0	0	0	2	1	1
General disorders and administration site conditions
Injection site reaction
subjects affected / exposed	42 / 545 (7.71%)	47 / 539 (8.72%)	5 / 286 (1.75%)	5 / 49 (10.20%)	0 / 67 (0.00%)	3 / 255 (1.18%)	5 / 85 (5.88%)	10 / 80 (12.50%)	2 / 47 (4.26%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	112	137	7	6	0	3	8	15	5	0	0	0	0	0
Application site rash
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Vaccination site pain
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	3 / 49 (6.12%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	4	0	0	0	0	0	0	0	0	2	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	3 / 49 (6.12%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	2 / 47 (4.26%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	2	0	0	0	1	0
Dyspnoea
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	1 / 8 (12.50%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	1
Epistaxis
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	2 / 8 (25.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	4 / 47 (8.51%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 23 (4.35%)	1 / 19 (5.26%)	1 / 8 (12.50%)
occurrences all number	0	0	0	1	0	0	0	0	6	0	0	1	1	1
Aspartate aminotransferase increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	5 / 47 (10.64%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	1 / 8 (12.50%)
occurrences all number	0	0	0	1	0	0	0	0	10	0	0	0	1	1
Blood beta-D-glucan increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	2 / 49 (4.08%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	2 / 47 (4.26%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	2 / 19 (10.53%)	1 / 8 (12.50%)
occurrences all number	0	0	0	2	0	0	0	0	3	0	1	0	2	1
Blood glucose increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	2 / 49 (4.08%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	3 / 47 (6.38%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	4	0	0	0	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	3 / 47 (6.38%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	4	0	0	0	0	0
Blood pressure increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Electrocardiogram T wave inversion
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Electrocardiogram abnormal
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Lipids abnormal
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Lymphocyte count decreased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	6 / 49 (12.24%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	6 / 47 (12.77%)	1 / 8 (12.50%)	0 / 6 (0.00%)	2 / 23 (8.70%)	1 / 19 (5.26%)	3 / 8 (37.50%)
occurrences all number	0	0	0	9	0	0	0	0	13	4	0	3	1	4
Low density lipoprotein increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	1 / 47 (2.13%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	2	1	0	0	1	0
Liver function test increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	2 / 19 (10.53%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Monocyte count decreased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	3 / 47 (6.38%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	4	0	0	0	1	0
Neutrophil count increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Protein urine present
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
White blood cell count decreased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	2 / 47 (4.26%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	7	0	1	0	1	0
White blood cell count increased
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Injury, poisoning and procedural complications
Cartilage injury
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Joint injury
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Spinal fracture
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Cardiac disorders
Bundle branch block right
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Sinus bradycardia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Ventricular tachycardia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	33 / 545 (6.06%)	19 / 539 (3.53%)	13 / 286 (4.55%)	3 / 49 (6.12%)	5 / 67 (7.46%)	0 / 255 (0.00%)	4 / 85 (4.71%)	5 / 80 (6.25%)	1 / 47 (2.13%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	36	23	15	3	5	0	5	6	3	0	0	0	0	1
Cervicobrachial syndrome
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Dizziness
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	4 / 49 (8.16%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	1 / 23 (4.35%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	6	0	0	0	0	0	1	0	1	0	0
Post herpetic neuralgia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Transient ischaemic attack
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Blood and lymphatic system disorders
Lymphopenia
subjects affected / exposed	33 / 545 (6.06%)	38 / 539 (7.05%)	24 / 286 (8.39%)	5 / 49 (10.20%)	4 / 67 (5.97%)	0 / 255 (0.00%)	8 / 85 (9.41%)	3 / 80 (3.75%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	45	57	32	12	5	0	9	5	0	0	0	0	0	0
Anaemia
subjects affected / exposed	35 / 545 (6.42%)	19 / 539 (3.53%)	8 / 286 (2.80%)	7 / 49 (14.29%)	2 / 67 (2.99%)	0 / 255 (0.00%)	1 / 85 (1.18%)	4 / 80 (5.00%)	4 / 47 (8.51%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 23 (4.35%)	1 / 19 (5.26%)	1 / 8 (12.50%)
occurrences all number	41	20	9	8	2	0	1	4	4	0	0	1	1	1
Leukopenia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	3 / 49 (6.12%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	1 / 47 (2.13%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	8	0	0	0	0	1	0	0	0	0	0
Eye disorders
Scleritis
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Abdominal pain
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Abdominal discomfort
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Constipation
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Irritable bowel syndrome
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Diarrhoea
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	2 / 49 (4.08%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	2 / 47 (4.26%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	1 / 8 (12.50%)
occurrences all number	0	0	0	2	0	0	0	0	2	0	0	0	1	1
Nausea
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	3 / 47 (6.38%)	0 / 8 (0.00%)	0 / 6 (0.00%)	2 / 23 (8.70%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	3	0	0	2	0	0
Salivary gland mass
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hepatobiliary disorders
Hepatic function abnormal
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	3 / 49 (6.12%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	1	0	0	0	0
Skin and subcutaneous tissue disorders
Drug eruption
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	0
Pruritus
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	3 / 47 (6.38%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	0	0	0	0	0
Rash
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Renal and urinary disorders
Renal impairment
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
subjects affected / exposed	41 / 545 (7.52%)	40 / 539 (7.42%)	20 / 286 (6.99%)	0 / 49 (0.00%)	6 / 67 (8.96%)	0 / 255 (0.00%)	3 / 85 (3.53%)	5 / 80 (6.25%)	3 / 47 (6.38%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	51	53	23	0	7	0	4	7	4	0	0	0	0	0
Back pain
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	1 / 47 (2.13%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	1 / 8 (12.50%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0	0	1	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Neck pain
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Osteoarthritis
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Spinal osteoarthritis
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Spondylolisthesis
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Infections and infestations
COVID-19
subjects affected / exposed	49 / 545 (8.99%)	32 / 539 (5.94%)	27 / 286 (9.44%)	5 / 49 (10.20%)	8 / 67 (11.94%)	0 / 255 (0.00%)	3 / 85 (3.53%)	4 / 80 (5.00%)	2 / 47 (4.26%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	51	35	27	5	8	0	3	4	2	1	0	0	1	0
Nasopharyngitis
subjects affected / exposed	28 / 545 (5.14%)	33 / 539 (6.12%)	15 / 286 (5.24%)	1 / 49 (2.04%)	5 / 67 (7.46%)	0 / 255 (0.00%)	5 / 85 (5.88%)	1 / 80 (1.25%)	2 / 47 (4.26%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	2 / 19 (10.53%)	0 / 8 (0.00%)
occurrences all number	33	43	15	1	8	0	7	1	2	0	0	0	2	0
Urinary tract infection
subjects affected / exposed	34 / 545 (6.24%)	39 / 539 (7.24%)	19 / 286 (6.64%)	4 / 49 (8.16%)	1 / 67 (1.49%)	0 / 255 (0.00%)	2 / 85 (2.35%)	6 / 80 (7.50%)	1 / 47 (2.13%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 23 (4.35%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	47	45	24	6	1	0	3	6	1	0	0	1	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	7 / 49 (14.29%)	1 / 67 (1.49%)	0 / 255 (0.00%)	5 / 85 (5.88%)	4 / 80 (5.00%)	4 / 47 (8.51%)	2 / 8 (25.00%)	1 / 6 (16.67%)	2 / 23 (8.70%)	3 / 19 (15.79%)	2 / 8 (25.00%)
occurrences all number	0	0	0	10	1	0	5	5	4	2	1	2	8	2
Herpes zoster
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	2 / 49 (4.08%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	1	0	1	0
Gingivitis
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	2 / 49 (4.08%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	1	0
Influenza
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	0
Pharyngitis
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Pneumonia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Sinusitis
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Hypercholesterolaemia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	1 / 49 (2.04%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	1 / 47 (2.13%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	2	1	0	0	1	0
Hyperlipidaemia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	2 / 49 (4.08%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	1 / 47 (2.13%)	0 / 8 (0.00%)	2 / 6 (33.33%)	0 / 23 (0.00%)	1 / 19 (5.26%)	1 / 8 (12.50%)
occurrences all number	0	0	0	2	0	0	0	0	2	0	2	0	1	1
Hypokalaemia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	4 / 49 (8.16%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 23 (0.00%)	1 / 19 (5.26%)	0 / 8 (0.00%)
occurrences all number	0	0	0	7	0	0	0	0	0	0	0	0	1	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 545 (0.00%)	0 / 539 (0.00%)	0 / 286 (0.00%)	0 / 49 (0.00%)	0 / 67 (0.00%)	0 / 255 (0.00%)	0 / 85 (0.00%)	0 / 80 (0.00%)	0 / 47 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 23 (0.00%)	0 / 19 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

22 May 2019

Correction of contraceptive requirements for Women of Child Bearing Potential (WOCBP) and additional clarifications.

21 Jan 2020

To detail revised risks, entry and stopping criteria following the update to comparator drug (tofacitinib) label. To introduce new medical device safety reporting wording, required in dvance of roll out of pre-filled syringes to this study. Other minor corrections and clarifications.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 superiority comparison with placebo (Global Cohort)

Primary: Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 superiority comparison with placebo (Global Cohort)

Primary: Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 (Asia Cohort)

Primary: Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 (Asia Cohort)

Secondary: Percentage of participants achieving Clinical disease activity index (CDAI) total score less than or equal to (<=)10 [CDAI Low disease activity (LDA)] at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving Clinical disease activity index (CDAI) total score less than or equal to (<=)10 [CDAI Low disease activity (LDA)] at Week 12 (Global Cohort)

Secondary: Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Global Cohort)

Secondary: Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving 20% improvement in ACR20 at Week 24: non-inferiority comparison with tofacitinib (Global Cohort)

Secondary: Percentage of participants achieving 20% improvement in ACR20 at Week 24: non-inferiority comparison with tofacitinib (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving 50%/70% improvement in American College of Rheumatology Criteria(ACR50/70) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving 50%/70% improvement in American College of Rheumatology Criteria(ACR50/70) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving ACR50/70 at Week 24 and ACR20/50/70 Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving ACR50/70 at Week 24 and ACR20/50/70 Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving ACR50/70 at Week 24 and ACR20/50/70 Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving ACR50/70 at Week 24 and ACR20/50/70 Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving a good/moderate European league against rheumatism (EULAR) response at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving a good/moderate European league against rheumatism (EULAR) response at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Number of participants achieving ACR/EULAR remission at Week 12 (Global Cohort)

Secondary: Number of participants achieving ACR/EULAR remission at Week 12 (Global Cohort)

Secondary: Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)

Secondary: Percentage of participants achieving no radiographic progression Van der Heijde modified total sharp scores (mTSS) <= 0.5) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving no radiographic progression Van der Heijde modified total sharp scores (mTSS) <= 0.5) at Week 12 (Global Cohort)

Secondary: Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for placebo switched arms (Global Cohort)

Secondary: Change from Baseline in CDAI total score at Week 12 (Global Cohort)

Secondary: Change from Baseline in CDAI total score at Week 12 (Global Cohort)

Secondary: Change from Baseline in CDAI total score at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort)