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Clinical Trial Results:
A Multi-Centre Long-term Extension Study to Assess the Safety and Efficacy of GSK3196165 in the Treatment of Rheumatoid Arthritis

Summary
EudraCT number	2019-000878-30
Trial protocol	LT GB CZ HU EE DE LV BG BE
Global end of trial date	24 Feb 2023

Results information
Results version number	v2(current)
This version publication date	06 Mar 2024
First version publication date	14 Dec 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

209564

ISRCTN number

US NCT number

NCT04333147

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

GreatWestRoad, Brentford,Middlesex, United Kingdom, TW8 9GS

Public contact

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

Scientific contact

GSK Response Center, GlaxoSmithKline, +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

12 May 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

24 Feb 2023

Was the trial ended prematurely?

Main objective of the trial

To determine the long-term safety of GSK3196165 at weekly doses of 90 milligram (mg) or 150 mg for the treatment of participants with moderately to severely active rheumatoid arthritis (RA).

Protection of trial subjects

Not Applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

14 Oct 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 803

Country: Number of subjects enrolled

Argentina: 387

Country: Number of subjects enrolled

United States: 344

Country: Number of subjects enrolled

Japan: 207

Country: Number of subjects enrolled

Russian Federation: 195

Country: Number of subjects enrolled

Ukraine: 165

Country: Number of subjects enrolled

Mexico: 124

Country: Number of subjects enrolled

South Africa: 93

Country: Number of subjects enrolled

China: 85

Country: Number of subjects enrolled

Czechia: 83

Country: Number of subjects enrolled

India: 82

Country: Number of subjects enrolled

Bulgaria: 58

Country: Number of subjects enrolled

Hungary: 57

Country: Number of subjects enrolled

Estonia: 38

Country: Number of subjects enrolled

Lithuania: 35

Country: Number of subjects enrolled

Colombia: 34

Country: Number of subjects enrolled

Korea, Republic of: 27

Country: Number of subjects enrolled

Germany: 23

Country: Number of subjects enrolled

Spain: 21

Country: Number of subjects enrolled

Serbia: 17

Country: Number of subjects enrolled

United Kingdom: 12

Country: Number of subjects enrolled

Latvia: 7

Country: Number of subjects enrolled

Thailand: 7

Country: Number of subjects enrolled

Malaysia: 5

Country: Number of subjects enrolled

Canada: 3

Country: Number of subjects enrolled

Australia: 2

Country: Number of subjects enrolled

Belgium: 1

Worldwide total number of subjects

2915

EEA total number of subjects

1126

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)

2275

From 65 to 84 years

639

85 years and over

Subject disposition

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Recruitment details

The participants with Rheumatoid Arthritis (RA) who completed the treatment phase of a qualifying Otilimab clinical study (201790 [ContRAst 1], 201791 [ContRAst 2] and 202018 [ContRAst 3]) and who, in the investigator's and participant's judgement would have benefited from extended treatment with Otilimab were enrolled.

Screening details

Participants from 202018, 201790, 201791 who consented, was enrolled. Participants who received Otilimab, continued on same dose. Participants who received comparator were randomized in ratio of 1:1 to either Otilimab 90 mg or 150 mg. One participant withdrew from 150mg GSK3196165 before receiving intervention due to Physician Decision (N=1459).

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, Monitor, Data analyst, Assessor

Are arms mutually exclusive

Yes

Otilimab 90 mg

Arm description

Participants who received Otilimab 90mg in a qualifying study and continued on Otilimab 90mg in study 209564 or participants who received either tofacitinib 5mg (study 201790 or 201791) or sarilumab 200mg (study 202018) in a qualifying study and were exposed for the first time to Otilimab 90mg in study 209564. Otilimab 90mg was administered through subcutaneous (SC) injection once weekly.

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.

Otilimab 150 mg

Arm description

Participants who received Otilimab 150mg in a qualifying study and continued on Otilimab 150mg in study 209564 or participants who received either tofacitinib 5mg (study 201790 or 201791) or sarilumab 200mg (study 202018) in a qualifying study and were exposed for the first time to Otilimab 150mg in study 209564. Otilimab 150mg was administered through subcutaneous (SC) injection once weekly.

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.

Number of subjects in period 1	Otilimab 90 mg	Otilimab 150 mg
Started	1456	1459
Completed	0	0
Not completed	1456	1459
Physician decision	17	20
Consent withdrawn by subject	65	68
Adverse event, non-fatal	43	40
STUDY TERMINATED BY SPONSOR	1251	1256
INVESTIGATOR SITE CLOSED	6	2
PROTOCOL-SPECIFIED WITHDRAWAL CRITERION MET	6	9
Lost to follow-up	19	16
Lack of efficacy	49	48

Baseline characteristics

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Reporting group title

Otilimab 90 mg

Reporting group description

Reporting group title

Otilimab 150 mg

Reporting group description

Reporting group values	Otilimab 90 mg	Otilimab 150 mg	Total
Number of subjects	1456	1459	2915
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	1138	1137	2275
From 65-84 years	318	321	639
85 years and over	0	1	1
Sex: Female, Male
Units: Participants
Female	1158	1181	2339
Male	298	278	576
Race/Ethnicity, Customized
Units: Subjects
AMERICAN INDIAN OR ALASKA NATIVE	40	53	93
ASIAN	223	206	429
BLACK OR AFRICAN AMERICAN	33	28	61
WHITE	1147	1157	2304
MULTIPLE	13	15	28
Age, Customized
Units: Subjects
18-49	453	402	855
50-64	685	735	1420
>=65	318	322	640
Age, Continuous
Units: YEARS
arithmetic mean (standard deviation)	55.2 ( 11.38 )	55.7 ( 10.91 )	-

End points

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Reporting group title

Otilimab 90 mg

Reporting group description

Reporting group title

Otilimab 150 mg

Reporting group description

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

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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) ^[1]

End point description

An AE is defined as 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. 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 the Safety Set that includes all randomized participants who received at least one dose of study treatment.

End point type

Primary

End point timeframe

Up to approximately 145 Weeks

Notes
[1] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1456	1459
Units: Participants
Participants with AEs, n=1456,1459	902	931
Participants with SAEs, n=1456,1459	123	114
Participants with AESI, n=1456,1459	120	95

No statistical analyses for this end point

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 24

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End point title

Change from Baseline in Hematology Parameter of Platelet Count at Week 24 ^[2]

End point description

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count. The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study treatment. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 24

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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1180	1204
Units: Giga cells per liter (10^9 cells/L)
arithmetic mean (standard deviation)	-11.9 ( 66.86 )	-9.7 ( 66.82 )

No statistical analyses for this end point

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 48

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End point title

Change from Baseline in Hematology Parameter of Platelet Count at Week 48 ^[3]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 48

Notes
[3] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	706	702
Units: Giga cells per liter (10^9 cells/L)
arithmetic mean (standard deviation)	-12.5 ( 66.47 )	-7.6 ( 71.36 )

No statistical analyses for this end point

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 96

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End point title

Change from Baseline in Hematology Parameter of Platelet Count at Week 96 ^[4]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 96

Notes
[4] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	125	117
Units: Giga cells per liter (10^9 cells/L)
arithmetic mean (standard deviation)	-13.8 ( 60.72 )	-5.7 ( 72.81 )

No statistical analyses for this end point

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 144

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End point title

Change from Baseline in Hematology Parameter of Platelet Count at Week 144 ^[5]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 144

Notes
[5] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1 ^[6]	2
Units: Giga cells per liter (10^9 cells/L)
arithmetic mean (standard deviation)	17.0 ( 0 )	-37.5 ( 40.31 )

Notes
[6] - The Standard Deviation was not derived as only one participant was analyzed.

No statistical analyses for this end point

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 24

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End point title

Change from Baseline in Hematology Parameter of Hemoglobin at Week 24 ^[7]

End point description

Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin. The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study treatment. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 24

Notes
[7] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1195	1212
Units: Gram Per Liter (g/L)
arithmetic mean (standard deviation)	0.4 ( 10.10 )	0.3 ( 9.89 )

No statistical analyses for this end point

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 48

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End point title

Change from Baseline in Hematology Parameter of Hemoglobin at Week 48 ^[8]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 48

Notes
[8] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	713	706
Units: Gram Per Liter (g/L)
arithmetic mean (standard deviation)	-0.5 ( 10.38 )	-1.1 ( 10.62 )

No statistical analyses for this end point

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 96

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End point title

Change from Baseline in Hematology Parameter of Hemoglobin at Week 96 ^[9]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 96

Notes
[9] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	127	119
Units: Gram Per Liter (g/L)
arithmetic mean (standard deviation)	1.0 ( 11.37 )	1.2 ( 10.24 )

No statistical analyses for this end point

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 24

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End point title

Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 24 ^[10]

End point description

Blood samples were collected for the assessment of change from baseline in hematology parameters including White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils. The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study treatment. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 24

Notes
[10] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1350	1212
Units: Giga cells per liter (10^9 cells/L)
arithmetic mean (standard deviation)
Neutrophils, n=1182, 1208	-0.348 ( 2.18 )	-0.390 ( 2.13 )
Lymphocytes, n=1182, 1208	-0.001 ( 0.55 )	-0.012 ( 0.55 )
Monocytes, n=1182, 1208	0.003 ( 0.18 )	0.00 ( 0.194 )
Eosinophils, n=1182, 666	0.027 ( 0.1623 )	0.022 ( 0.171 )
Basophils, n=1350, 1208	-0.001 ( 0.0405 )	-0.001 ( 0.04 )
Total WBC, n=1188, 1212	-0.32 ( 2.212 )	-0.38 ( 2.230 )

No statistical analyses for this end point

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 144

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End point title

Change from Baseline in Hematology Parameter of Hemoglobin at Week 144 ^[11]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 144

Notes
[11] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1 ^[12]	2
Units: Gram Per Liter (g/L)
arithmetic mean (standard deviation)	-1.0 ( 0 )	2.0 ( 2.83 )

Notes
[12] - The Standard Deviation was not derived as only one participant was analyzed.

No statistical analyses for this end point

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 96

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End point title

Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 96 ^[13]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 96

Notes
[13] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	127	119
Units: Giga cells per liter (10^9 cells/L)
arithmetic mean (standard deviation)
Neutrophils, n=127,44	-0.243 ( 1.8851 )	-0.555 ( 2.3580 )
Lymphocytes, n=127,118	0.090 ( 0.6453 )	0.018 ( 0.5816 )
Monocytes, n=127,118	-0.042 ( 0.2001 )	-0.001 ( 0.2035 )
Eosinophils, n=127,118	0.025 ( 0.1725 )	0.029 ( 0.1526 )
Basophils, n=127,118	-0.007 ( 0.0423 )	-0.013 ( 0.0346 )
Total WBC, n=127,119	-0.18 ( 2.043 )	-0.53 ( 2.568 )

No statistical analyses for this end point

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 48

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End point title

Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 48 ^[14]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 48

Notes
[14] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	709	703
Units: Giga cells per liter (10^9 cells/L)
arithmetic mean (standard deviation)
Neutrophils, n=703, 698	-0.318 ( 2.2215 )	-0.541 ( 2.1426 )
Lymphocytes, n=703, 698	-0.022 ( 0.5385 )	-0.051 ( 0.5725 )
Monocytes, n=703, 698	-0.002 ( 0.1871 )	-0.013 ( 0.2461 )
Eosinophils, n=703, 698	0.018 ( 0.1435 )	0.028 ( 0.1844 )
Basophils, n=703, 698	-0.004 ( 0.0391 )	-0.006 ( 0.0403 )
Total WBC, n=709, 703	-0.33 ( 2.283 )	-0.58 ( 2.262 )

No statistical analyses for this end point

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 144

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End point title

Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 144 ^[15]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 144

Notes
[15] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1 ^[16]	2 ^[17]
Units: Giga cells per liter (10^9 cells/L)
arithmetic mean (standard deviation)
Neutrophils, n=1,0	-0.360 ( 0 )	0 ( 0 )
Lymphocytes, n=1,2	-0.320 ( 0 )	0.010 ( 0.3253 )
Monocytes, n=1,2	-0.220 ( 0 )	0.010 ( 0.0424 )
Eosinophils, n=1,0	-0.130 ( 0 )	0 ( 0 )
Basophils, n=1,2	0.000 ( 0 )	0.000 ( 0.0141 )
Total WBC, n=1,2	-1.00 ( 0 )	-0.85 ( 1.061 )

Notes
[16] - The Standard Deviation was not derived as only one participant was analyzed.
[17] - There is no data to disclose as no participant was analyzed for some of the analytes.

No statistical analyses for this end point

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 24

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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 Transferase (GGT), Creatine Kinase (CPK) at Week 24 ^[18]

End point description

Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including AST, ALT, AP, GGT, CPK. The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study treatment. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 24

Notes
[18] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1232	1402
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
Aspartate Aminotransferase (AST), n=1231,1242	1.0 ( 11.09 )	0.8 ( 9.70 )
Alanine Aminotransferase (ALT), n=1232,1243	0.0 ( 15.80 )	-0.1 ( 15.20 )
Alkaline Phosphatase (AP), n=1232,12423	3.0 ( 18.85 )	3.1 ( 21.05 )
Gamma Glutamyl Transferase (GGT), n=1230,1402	-0.9 ( 20.32 )	-0.4 ( 18.94 )
Creatine Kinase (CPK), n=1230,1242	5.4 ( 103.03 )	-3.8 ( 66.66 )

No statistical analyses for this end point

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 96

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End point title

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 96

Notes
[19] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	128	122
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
Aspartate Aminotransferase (AST), n=128,44	0.1 ( 11.65 )	2.0 ( 7.47 )
Alanine Aminotransferase (ALT), n=128,44	-2.4 ( 19.02 )	-1.1 ( 9.33 )
Alkaline Phosphatase (AP), n=128,122	0.0 ( 18.98 )	8.6 ( 27.79 )
Gamma Glutamyl Transferase (GGT), n=128,122	-1.9 ( 18.52 )	-0.1 ( 19.67 )
Creatine Kinase (CPK), n=128,122	1.4 ( 39.73 )	3.6 ( 93.29 )

No statistical analyses for this end point

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 48

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End point title

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 48

Notes
[20] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	762	749
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
Aspartate Aminotransferase (AST), n=761,749	0.4 ( 11.11 )	0.4 ( 11.32 )
Alanine Aminotransferase (ALT), n=762,748	-0.9 ( 16.35 )	-1.2 ( 16.26 )
Alkaline Phosphatase (AP), n=762,748	5.4 ( 20.07 )	5.2 ( 21.32 )
Gamma Glutamyl Transferase (GGT), n=762,748	-0.0 ( 22.44 )	-0.4 ( 22.14 )
Creatine Kinase (CPK), n=762,748	7.8 ( 153.24 )	-3.7 ( 71.52 )

No statistical analyses for this end point

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 144

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End point title

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 144

Notes
[21] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1 ^[22]	2 ^[23]
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
Aspartate Aminotransferase (AST), n=1,2	-8.0 ( 0 )	2.0 ( 0.0 )
Alanine Aminotransferase (ALT), n=1,0	-14.0 ( 0 )	0 ( 0 )
Alkaline Phosphatase (AP), n=1,2	39.0 ( 0 )	-1.5 ( 6.36 )
Gamma Glutamyl Transferase (GGT), n=1,2	-21.0 ( 0 )	5.0 ( 14.14 )
Creatine Kinase (CPK), n=1,2	-47.0 ( 0 )	-2.5 ( 31.82 )

Notes
[22] - The Standard Deviation was not derived as only one participant was analyzed.
[23] - There is no data to disclose as no participant was analyzed for some of the analytes.

No statistical analyses for this end point

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 24

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End point title

Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 24 ^[24]

End point description

Blood samples was collected for the assessment of clinical chemistry parameters including Cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol (HDL), Triglycerides. The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study treatment. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 24

Notes
[24] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1183	1204
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
Cholesterol, n=1183,1201	-0.038 ( 0.8542 )	-0.011 ( 0.9685 )
HDL Cholesterol, Direct, n=1183,1201	-0.020 ( 0.2703 )	-0.022 ( 0.2869 )
LDL Cholesterol, n=1171,1190	-0.031 ( 0.7239 )	0.010 ( 0.7818 )
Triglycerides, n=1183, 1204	0.033 ( 0.6503 )	0.011 ( 0.7895 )

No statistical analyses for this end point

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 48

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End point title

Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 48 ^[25]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 48

Notes
[25] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	730	719
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
Cholesterol, n=730,718	-0.053 ( 0.9271 )	-0.078 ( 0.9826 )
HDL Cholesterol, Direct, n=730,718	-0.021 ( 0.2979 )	-0.027 ( 0.2959 )
LDL Cholesterol, n=728,708	-0.038 ( 0.7865 )	-0.034 ( 0.7899 )
Triglycerides, n=730,719	0.015 ( 0.6772 )	-0.019 ( 0.7376 )

No statistical analyses for this end point

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 144

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End point title

Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 144 ^[26]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 144

Notes
[26] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1 ^[27]	2
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
Cholesterol, n=1,2	-2.360 ( 0 )	-2.240 ( 2.8709 )
HDL Cholesterol, Direct, n=1,2	0.160 ( 0 )	-0.095 ( 0.0212 )
LDL Cholesterol, n=1,2	-2.250 ( 0 )	-1.750 ( 2.4183 )
Triglycerides, n=1,2	-0.580 ( 0 )	-0.865 ( 0.9687 )

Notes
[27] - The Standard Deviation was not derived as only one participant was analyzed.

No statistical analyses for this end point

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 96

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End point title

Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 96 ^[28]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 96

Notes
[28] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	113	100
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
Cholesterol, n=113,100	-0.178 ( 1.0350 )	-0.130 ( 1.0570 )
HDL Cholesterol, Direct, n=113,100	-0.032 ( 0.2665 )	-0.058 ( 0.3233 )
LDL Cholesterol, n=112,99	-0.159 ( 0.8948 )	-0.031 ( 0.8546 )
Triglycerides, n=113,100	0.009 ( 0.8042 )	-0.056 ( 0.7262 )

No statistical analyses for this end point

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 24

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End point title

Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 24 ^[29]

End point description

Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including total bilirubin, direct bilirubin. The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study treatment. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 24

Notes
[29] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1232	1243
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)
Total Bilirubin, n=1232,1243	0.3 ( 2.87 )	0.3 ( 2.92 )
Direct Bilirubin, n=1224,1235	0.053 ( 0.764 )	0.027 ( 0.641 )

No statistical analyses for this end point

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 48

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End point title

Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 48 ^[30]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 48

Notes
[30] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	762	749
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)
Total Bilirubin, n=762,749	-0.0 ( 2.85 )	0.1 ( 3.04 )
Direct Bilirubin, n=757,743	0.011 ( 0.777 )	0.040 ( 0.690 )

No statistical analyses for this end point

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 144

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End point title

Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 144 ^[31]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 144

Notes
[31] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1 ^[32]	2
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)
Total Bilirubin, n=1,2	4.0 ( 0 )	4.5 ( 6.36 )
Direct Bilirubin, n=1,2	2.000 ( 0 )	1.500 ( 0.707 )

Notes
[32] - The Standard Deviation was not derived as only one participant was analyzed.

No statistical analyses for this end point

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

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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 ^[33]

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.

End point type

Primary

End point timeframe

Up to approximately 145 Weeks

Notes
[33] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1456	1459
Units: Participants
Hypercalcemia, Total, Grade 3	1	0
Hyperkalemia, Total, Grade 4	2	0
Hypernatremia, Total, Grade 3	1	0
Hypernatremia, Total, Grade 4	0	1
Chronic Kidney Disease, Total, Grade 3	0	1
Creatinine increased, Total, Grade 3	1	0

No statistical analyses for this end point

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 96

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End point title

Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 96 ^[34]

End point description

End point type

Primary

End point timeframe

Baseline (Day 01) and Week 96

Notes
[34] - 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: This endpoint was descriptive; hence no statistical analysis to report.

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	128	123
Units: Micromoles per liter (umol/L)
arithmetic mean (standard deviation)
Total Bilirubin, n=128, 123	-0.2 ( 3.22 )	0.5 ( 3.49 )
Direct Bilirubin, n=127, 122	0.047 ( 0.815 )	0.041 ( 0.827 )

No statistical analyses for this end point

Secondary: Percentage of participants achieving Clinical Disease Activity Index (CDAI) total score lesser than or equal to (<=)10 (CDAI) low disease activity (LDA) at Week 24, 48, 96 and 144

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End point title

Percentage of participants achieving Clinical Disease Activity Index (CDAI) total score lesser than or equal to (<=)10 (CDAI) low disease activity (LDA) at Week 24, 48, 96 and 144

End point description

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 the intent to treat (ITT) set that includes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1206 ^[35]	1212
Units: Percentage of participants
number (not applicable)
Week 24, n=1206,1212	47.0	46.0
Week 48, n=757,749	44.0	47.0
Week 96, n=124,112	40.0	47.0
Week 144, n=0,1	0	0.0

Notes
[35] - There is no data to disclose as no participant was analyzed at Week 144.

No statistical analyses for this end point

Secondary: Percentage of participants achieving Clinical Disease Activity Index (CDAI) total score <=2.8 (CDAI Remission) at Week 24, 48, 96 and 144

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End point title

Percentage of participants achieving Clinical Disease Activity Index (CDAI) total score <=2.8 (CDAI Remission) at Week 24, 48, 96 and 144

End point description

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 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1206 ^[36]	1212
Units: Percentage of participants
number (not applicable)
Week 24, n=1206,1212	11.0	10.0
Week 48, n=757,749	12.0	9.0
Week 96, n=124,112	13.0	9.0
Week 144, n=0,1	0	0.0

Notes
[36] - There is no data to disclose as no participant was analyzed at Week 144.

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) <2.6 at Week 24, 48, 96 and 144

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End point title

Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <2.6 at Week 24, 48, 96 and 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). PtGA is transformed to a 0-10 scale before computing the total score. DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicates 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 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1190	1190
Units: Percentage of participants
number (not applicable)
Week 24, n=1190,1190	26.0	25.0
Week 48, n=719,715	25.0	25.0
Week 96, n=108,99	26.0	28.0
Week 144, n=0,1	0	0.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving Disease Activity Score using 28 joint count and Erythrocyte Sedimentation Rate (ESR) <2.6 (DAS28-ESR Remission) at Week 24, 48, 96 and 132

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End point title

Percentage of participants achieving Disease Activity Score using 28 joint count and Erythrocyte Sedimentation Rate (ESR) <2.6 (DAS28-ESR Remission) at Week 24, 48, 96 and 132

End point description

The DAS28-ESR is a measure of RA disease activity calculated using TJC28,SJC28, ESR (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). PtGA is transformed to a 0-10 scale before computing the total score. 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 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 132

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1084	1085
Units: Percentage of participants
number (not applicable)
Week 24, n=1084,1085	15.0	14.0
Week 48, n=676,672	14.0	13.0
Week 96, n=95,91	16.0	12.0
Week 132, n=1,3	0.0	33.0

No statistical analyses for this end point

Secondary: Percentage of participants achieving American College of Rheumatology (ACR)/ European league against rheumatism (EULAR) remission at Week 24, 48, 96 and 144

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End point title

Percentage of participants achieving American College of Rheumatology (ACR)/ European league against rheumatism (EULAR) remission at Week 24, 48, 96 and 144

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. Simple Disease Activity Index based ACR/EULAR remission is achieved if a has SDAI <= 3.3. The SDAI is the sum of the tender/painful joint count and swollen joint count, employing 28 joints; PtGA and PhGA (on a scale of 0-10); and hsCRP (mg/L). Percentage values are rounded off. 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1190	1199
Units: Percentage of participants
number (not applicable)
Boolean-based ACR/EULAR, Week 24, n=1190,1199	7.0	6.0
Boolean-based ACR/EULAR, Week 48, n=719,715	8.0	4.0
Boolean-based ACR/EULAR, Week 96, n=108,99	8.0	9.0
Boolean-based ACR/EULAR, Week 144, n=0,1	0.0	0.0

No statistical analyses for this end point

Secondary: Absolute Values for Clinical Disease Activity Index (CDAI) total score

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End point title

Absolute Values for Clinical Disease Activity Index (CDAI) total score

End point description

CDAI total score is a composite score consisting of the sum of TJC28, TJC28, PtGA (visual analogue scale with values from 0=best to 100=worst) and 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. 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1206 ^[37]	1212 ^[38]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=1206,1212	13.42 ( 10.669 )	14.26 ( 11.637 )
Week 48, n=757,749	13.85 ( 10.612 )	14.07 ( 11.186 )
Week 96, n=124,112	14.62 ( 11.443 )	15.22 ( 13.997 )
Week 144, n=0,1	0 ( 0 )	11.30 ( 0.0 )

Notes
[37] - At Week 144, there were 0 participant analyzed, there is no data to disclose.
[38] - At Week 144, as only single participant was analyzed the standard deviation was be derived.

No statistical analyses for this end point

Secondary: Absolute Values for Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP)

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End point title

Absolute Values for Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP)

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). PtGA is transformed to a 0-10 scale before computing the total score. DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1338 ^[39]	1199 ^[40]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=1338,1199	3.49 ( 1.237 )	3.55 ( 1.269 )
Week 48, n=719,715	3.51 ( 1.224 )	3.54 ( 1.232 )
Week 96, n=108,99	3.44 ( 1.188 )	3.52 ( 1.389 )
Week 144, n=0,1	0.0 ( 0.0 )	3.21 ( 0.0 )

Notes
[39] - At Week 144, there were 0 participant analyzed, there is no data to disclose.
[40] - At Week 144, as only single participant was analyzed the standard deviation was be derived.

No statistical analyses for this end point

Secondary: Absolute Values for Disease Activity Score using 28 joint count and Erythrocyte Sedimentation Rate (DAS28-ESR)

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End point title

Absolute Values for Disease Activity Score using 28 joint count and Erythrocyte Sedimentation Rate (DAS28-ESR)

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). PtGA is transformed to a 0-10 scale before computing the total score. DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 132

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1084 ^[41]	1085
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=1084,1085	3.97 ( 1.295 )	4.01 ( 1.333 )
Week 48, n=676,672	4.02 ( 1.284 )	4.05 ( 1.306 )
Week 96, n=95,91	3.92 ( 1.216 )	4.04 ( 1.470 )
Week 132, n=1,3	3.77 ( 0 )	4.26 ( 1.560 )

Notes
[41] - At Week 132, as only single participant was analyzed the standard deviation was be derived.

No statistical analyses for this end point

Secondary: Absolute values for Health Assessment Questionnaire Disability Index (HAQ-DI)

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End point title

Absolute values for Health Assessment Questionnaire Disability Index (HAQ-DI)

End point description

The HAQ-DI includes 20 questions which assesses difficulty in performing activities of daily living. The questionnaire assesses eight domains of physical functioning: Dressing and Grooming, Hygiene, Arising, Reach, Eating, Grip, Walking, Common Daily Activities. The questions assess domain scores ranging from 0 "without any difficulty" to 3 "unable to do." Scores on each domain were summed and averaged to provide an overall score ranging from 0 to 3, where higher score reflected worse status and a lower score indicates better quality of life.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1228 ^[42]	1239 ^[43]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=1228,1239	1.045 ( 0.6764 )	1.060 ( 0.6849 )
Week 48, n=768,764	1.072 ( 0.6679 )	1.096 ( 0.6691 )
Week 96, n=126,120	1.074 ( 0.6852 )	1.156 ( 0.7582 )
Week 144, n=0,1	0 ( 0 )	2.00 ( 0 )

Notes
[42] - At Week 144, there were 0 participant analyzed, there is no data to disclose.
[43] - At Week 144, as only single participant was analyzed the standard deviation was be derived.

No statistical analyses for this end point

Secondary: Absolute values of Van der Heijde modified total sharp scores (mTSS)

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End point title

Absolute values of Van der Heijde modified total sharp scores (mTSS)

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. The analysis was performed on the ITT set that includes participants from qualifying studies 201790 and 201791 only who received at least one dose of study treatment. This population was based on the treatment the subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24 and 48

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	66	46
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=66,46	23.26 ( 34.191 )	30.31 ( 40.236 )
Week 48, n=66,46	23.27 ( 33.953 )	30.34 ( 40.432 )

No statistical analyses for this end point

Secondary: Absolute values for Arthritis pain VAS

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End point title

Absolute values for Arthritis pain VAS

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. 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1230 ^[44]	1239 ^[45]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=1230,1239	34.6 ( 23.51 )	36.6 ( 23.85 )
Week 48, n=768,765	37.0 ( 23.55 )	36.0 ( 23.88 )
Week 96, n=127,119	39.3 ( 24.62 )	38.1 ( 27.08 )
Week 144, n=0,1	0 ( 0 )	26.0 ( 0 )

Notes
[44] - At Week 144, there were 0 participant analyzed, there is no data to disclose.
[45] - At Week 144, as only single participant was analyzed the standard deviation was be derived.

No statistical analyses for this end point

Secondary: Absolute values SF-36 domain scores

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End point title

Absolute values SF-36 domain scores

End point description

SF-36 is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). 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. Quality Metric software was used for scoring for SF-36. The analysis was performed on ITT set that includes all randomized participants who received at least one dose of study treatment. This population was based on treatment the subject was randomized to. Number of subjects analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1228 ^[46]	1237 ^[47]
Units: Scores on a scale
arithmetic mean (standard deviation)
Bodily Pain at Week 24, n=1228,1237	54.49 ( 21.457 )	53.83 ( 21.158 )
Bodily Pain at Week 48, n=768,764	52.22 ( 21.099 )	52.94 ( 21.158 )
Bodily Pain at Week 96, n=126,119	49.90 ( 20.943 )	51.11 ( 21.983 )
Bodily Pain at Week 144, n=0,1	0 ( 0 )	41.00 ( 0 )
General Health at week 24, n=1228,1237	51.00 ( 18.744 )	50.30 ( 17.980 )
General Health at week 48, n=768,764	50.35 ( 18.817 )	49.44 ( 17.645 )
General Health at week 96, n=126,119	48.44 ( 20.029 )	46.73 ( 18.543 )
General Health at week 144, n=0,1	0 ( 0 )	45.00 ( 0 )
Mental Health at week 24, n=1228,1237	67.47 ( 19.387 )	68.05 ( 19.150 )
Mental Health at week 48, n=768,764	67.64 ( 19.701 )	67.97 ( 19.636 )
Mental Health at week 96, n=126,119	66.90 ( 20.860 )	68.49 ( 20.217 )
Mental Health at week 144, n=0,1	0 ( 0 )	50.00 ( 0 )
Physical Function at week 24, n=1228,1237	56.20 ( 25.644 )	55.28 ( 25.615 )
Physical Function at week 48, n=768,764	54.23 ( 26.222 )	53.98 ( 25.397 )
Physical Function at week 96, n=126,119	51.87 ( 25.735 )	50.92 ( 26.175 )
Physical Function at week 144, n=0,1	0 ( 0 )	35.00 ( 0 )
Role Emotional At week 24, n=1228,1237	74.79 ( 24.653 )	75.09 ( 24.760 )
Role Emotional At week 48, n=768,764	75.31 ( 24.008 )	76.18 ( 24.163 )
Role Emotional At week 96, n=126,119	73.35 ( 25.188 )	74.44 ( 26.324 )
Role Emotional At week 144, n=0,1	0 ( 0 )	50.00 ( 0 )
Role Physical at week 24, n=1228,1237	58.58 ( 23.155 )	57.78 ( 23.514 )
Role Physical at week 48, n=768,764	56.49 ( 23.645 )	57.57 ( 23.463 )
Role Physical at week 96, n=126,119	54.27 ( 23.818 )	55.15 ( 24.956 )
Role Physical at week 144, n=0,1	0 ( 0 )	25.00 ( 0 )
Social Function at week 24, n=1228,1237	71.20 ( 24.001 )	71.39 ( 23.936 )
Social Function at week 48, n=768,764	70.88 ( 24.596 )	71.29 ( 24.123 )
Social Function at week 96, n=126,119	68.25 ( 24.065 )	69.43 ( 26.526 )
Social Function at week 144, n=0,1	0 ( 0 )	62.50 ( 0 )
Vitality at week 24, n=1228,1237	55.77 ( 20.690 )	55.18 ( 20.593 )
Vitality at week 48, n=768,764	55.24 ( 20.972 )	54.49 ( 21.262 )
Vitality at week 96, n=126,119	51.04 ( 23.127 )	54.25 ( 22.738 )
Vitality at week 144, n=0,1	0 ( 0 )	50.00 ( 0 )

Notes
[46] - At Week 144, there were 0 participant analyzed, there is no data to disclose.
[47] - At Week 144, as only single participant was analyzed the standard deviation was be derived.

No statistical analyses for this end point

Secondary: Absolute values Short form (SF)-36 Mental Component Scores (MCS)

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End point title

Absolute values Short form (SF)-36 Mental Component Scores (MCS)

End point description

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,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,vitality,MH,role-emotional) representing overall mental health. Quality Metric software was used for scoring.- 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1228 ^[48]	1237 ^[49]
Units: T-score
arithmetic mean (standard deviation)
Week 24, n=1228,1237	49.14 ( 10.386 )	49.44 ( 10.384 )
Week 48, n=768,764	49.54 ( 10.577 )	49.70 ( 10.557 )
Week 96, n=126,119	48.66 ( 11.483 )	49.75 ( 11.351 )
Week 144, n=0,1	0 ( 0 )	42.55 ( 0 )

Notes
[48] - At Week 144, there were 0 participant analyzed, there is no data to disclose.
[49] - At Week 144, as only single participant was analyzed the standard deviation was be derived.

No statistical analyses for this end point

Secondary: Absolute values SF-36 Physical Component Scores (PCS)

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End point title

Absolute values SF-36 Physical Component Scores (PCS)

End point description

SF-36 is 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,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. Quality Metric software was used for scoring. 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1228 ^[50]	1237 ^[51]
Units: T-Score
arithmetic mean (standard deviation)
Week 24, n=1228,1237	41.19 ( 8.173 )	40.67 ( 8.232 )
Week 48, n=768,764	40.17 ( 8.586 )	40.13 ( 8.271 )
Week 96, n=126,119	39.18 ( 9.280 )	38.86 ( 8.879 )
Week 144, n=0,1	0 ( 0 )	35.03 ( 0 )

Notes
[50] - At Week 144, there were 0 participant analyzed, there is no data to disclose.
[51] - At Week 144, as only single participant was analyzed the standard deviation was be derived.

No statistical analyses for this end point

Secondary: Absolute values Functional assessment of chronic illness therapy (FACIT)-Fatigue

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End point title

Absolute values Functional assessment of chronic illness therapy (FACIT)-Fatigue

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. 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 subject was randomized to. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

End point type

Secondary

End point timeframe

Week 24, 48, 96 and 144

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1229 ^[52]	1238 ^[53]
Units: Scores on a scale
arithmetic mean (standard deviation)
Week 24, n=1229,1238	36.0 ( 10.33 )	35.9 ( 10.25 )
Week 48, n=767,764	35.5 ( 10.53 )	35.4 ( 10.59 )
Week 96, n=126,119	35.2 ( 10.77 )	34.8 ( 11.87 )
Week 144, n=0,1	0 ( 0 )	26.0 ( 0 )

Notes
[52] - At Week 144, there were 0 participant analyzed, there is no data to disclose.
[53] - At Week 144, as only single participant was analyzed the standard deviation was be derived.

No statistical analyses for this end point

Secondary: Number of participants with anti-GSK3196165 antibodies

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End point title

Number of participants with anti-GSK3196165 antibodies

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. 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 subject was randomized to.

End point type

Secondary

End point timeframe

Week 120

End point values	Otilimab 90 mg	Otilimab 150 mg
Number of subjects analysed	1456	1459
Units: Participants	11	10

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All AE and SAE were collected from the start of the study intervention. Initially the study was planned for 4 years approx. 208 weeks however due to early termination by sponsor data for all Adverse event was collected up to approximately 145 weeks only.

Assessment type

Systematic

Dictionary name

Medra

Dictionary version

25.0

Reporting group title

Otilimab 150 mg

Reporting group description

Participants received 150mg Otilimab prior to this study 209564 and received either tofacitinib (study 201790 or 201791) or sarilumab (study 202018) in the qualifying studies and were exposed for the first time to Otilimab through subcutaneous (SC) injection once weekly.

Reporting group title

Otilimab 90 mg

Reporting group description

Participants received 90mg Otilimab prior to this study 209564 and received either tofacitinib (study 201790 or 201791) or sarilumab (study 202018) in the qualifying studies and were exposed for the first time to Otilimab through subcutaneous (SC) injection once weekly.

Serious adverse events	Otilimab 150 mg	Otilimab 90 mg
Total subjects affected by serious adverse events
subjects affected / exposed	114 / 1459 (7.81%)	123 / 1456 (8.45%)
number of deaths (all causes)	9	10
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adenocarcinoma of appendix
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adenocarcinoma pancreas
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Anogenital warts
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Invasive ductal breast carcinoma
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Invasive lobular breast carcinoma
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung adenocarcinoma
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphoproliferative disorder
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian cancer stage III
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatic neoplasm
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatic neuroendocrine tumour
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Squamous cell carcinoma of the cervix
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transitional cell carcinoma
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	1 / 1459 (0.07%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Intraductal papillary-mucinous carcinoma of pancreas
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Peripheral arterial occlusive disease
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Brachiocephalic vein thrombosis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	2 / 1459 (0.14%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Varicose vein
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subclavian vein thrombosis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperthermia
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 1459 (0.00%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden death
subjects affected / exposed	1 / 1459 (0.07%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 2
Reproductive system and breast disorders
Cystocele
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Adnexal torsion
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cervical dysplasia
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endometrial hyperplasia
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Menstrual disorder
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian cyst
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Postmenopausal haemorrhage
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rectocele
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine cyst
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine polyp
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endometriosis
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Laryngeal ulceration
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal polyps
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal turbinate hypertrophy
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	3 / 1459 (0.21%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	1 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Generalised anxiety disorder
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transient psychosis
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Product issues
Device physical property issue
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Accidental poisoning
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Acetabulum fracture
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Burns first degree
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dislocation of vertebra
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	3 / 1459 (0.21%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	3 / 1459 (0.21%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fracture
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Incisional hernia
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ligament injury
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Limb injury
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Periprosthetic osteolysis
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural complication
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	0 / 1459 (0.00%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Wound
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	3 / 1459 (0.21%)	3 / 1456 (0.21%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	2 / 1459 (0.14%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Myocardial infarction
subjects affected / exposed	2 / 1459 (0.14%)	3 / 1456 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 2	0 / 1
Atrial fibrillation
subjects affected / exposed	1 / 1459 (0.07%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Epilepsy
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Carotid artery disease
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Carpal tunnel syndrome
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cervical radiculopathy
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbosacral radiculopathy
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Myelopathy
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	3 / 1459 (0.21%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vertebrobasilar insufficiency
subjects affected / exposed	0 / 1459 (0.00%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Blood and lymphatic system disorders
Anaemia vitamin B12 deficiency
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eosinophilia
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Meniere's disease
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tympanic membrane perforation
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vestibular disorder
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Retinal artery occlusion
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
subjects affected / exposed	2 / 1459 (0.14%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Jejunal perforation
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestinal obstruction
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal incarcerated hernia
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum
subjects affected / exposed	0 / 1459 (0.00%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum intestinal
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterovesical fistula
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Flatulence
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric ulcer
subjects affected / exposed	0 / 1459 (0.00%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 1459 (0.00%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis haemorrhagic
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophageal rupture
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis chronic
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peptic ulcer
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Omental haemorrhage
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	2 / 1459 (0.14%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic cirrhosis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Renal and urinary disorders
Calculus urinary
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	1 / 1459 (0.07%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Renal colic
subjects affected / exposed	2 / 1459 (0.14%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Flank pain
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Foot deformity
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc degeneration
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc disorder
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 1459 (0.00%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Joint destruction
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle spasms
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	8 / 1459 (0.55%)	6 / 1456 (0.41%)
occurrences causally related to treatment / all	0 / 11	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoporotic fracture
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	4 / 1459 (0.27%)	7 / 1456 (0.48%)
occurrences causally related to treatment / all	1 / 4	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Synovial cyst
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bursitis
subjects affected / exposed	2 / 1459 (0.14%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Bacterial infection
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess bacterial
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anastomotic infection
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bursitis infective
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	10 / 1459 (0.69%)	8 / 1456 (0.55%)
occurrences causally related to treatment / all	0 / 10	0 / 8
deaths causally related to treatment / all	0 / 3	0 / 1
Cellulitis
subjects affected / exposed	0 / 1459 (0.00%)	3 / 1456 (0.21%)
occurrences causally related to treatment / all	0 / 0	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic gangrene
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterobacter bacteraemia
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia pyelonephritis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis salmonella
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster disseminated
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral discitis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Latent tuberculosis
subjects affected / exposed	1 / 1459 (0.07%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung abscess
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mastoiditis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	2 / 1459 (0.14%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	5 / 1459 (0.34%)	5 / 1456 (0.34%)
occurrences causally related to treatment / all	2 / 5	2 / 5
deaths causally related to treatment / all	0 / 1	0 / 0
COVID-19
subjects affected / exposed	1 / 1459 (0.07%)	4 / 1456 (0.27%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 2
Pneumonia respiratory syncytial viral
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural infection
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	0 / 1459 (0.00%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection viral
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	2 / 1459 (0.14%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal sepsis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Subcutaneous abscess
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tubo-ovarian abscess
subjects affected / exposed	1 / 1459 (0.07%)	0 / 1456 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 1459 (0.00%)	2 / 1456 (0.14%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Viral sinusitis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetic ketoacidosis
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 1459 (0.00%)	1 / 1456 (0.07%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Otilimab 150 mg	Otilimab 90 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	308 / 1459 (21.11%)	279 / 1456 (19.16%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
subjects affected / exposed	129 / 1459 (8.84%)	118 / 1456 (8.10%)
occurrences all number	175	158
Infections and infestations
COVID-19
subjects affected / exposed	141 / 1459 (9.66%)	141 / 1456 (9.68%)
occurrences all number	148	153
Upper respiratory tract infection
subjects affected / exposed	88 / 1459 (6.03%)	65 / 1456 (4.46%)
occurrences all number	100	74

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Were there any global substantial amendments to the protocol? No

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

Clinical Trial Results: A Multi-Centre Long-term Extension Study to Assess the Safety and Efficacy of GSK3196165 in the Treatment of Rheumatoid Arthritis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 24

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 24

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 48

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 48

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 96

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 96

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 144

Primary: Change from Baseline in Hematology Parameter of Platelet Count at Week 144

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 24

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 24

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 48

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 48

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 96

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 96

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 24

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 24

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 144

Primary: Change from Baseline in Hematology Parameter of Hemoglobin at Week 144

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 96

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 96

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 48

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 48

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 144

Primary: Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 144

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 24

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 24

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 96

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 96

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 48

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 48

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 144

Primary: Change from Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 144

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 24

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 24

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 48

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 48

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 144

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 144

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 96

Primary: Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 96

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 24

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 24

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 48

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 48

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 144

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 144

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

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

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 96

Primary: Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 96

Secondary: Percentage of participants achieving Clinical Disease Activity Index (CDAI) total score lesser than or equal to (<=)10 (CDAI) low disease activity (LDA) at Week 24, 48, 96 and 144

Secondary: Percentage of participants achieving Clinical Disease Activity Index (CDAI) total score lesser than or equal to (<=)10 (CDAI) low disease activity (LDA) at Week 24, 48, 96 and 144

Secondary: Percentage of participants achieving Clinical Disease Activity Index (CDAI) total score <=2.8 (CDAI Remission) at Week 24, 48, 96 and 144

Secondary: Percentage of participants achieving Clinical Disease Activity Index (CDAI) total score <=2.8 (CDAI Remission) at Week 24, 48, 96 and 144

Secondary: Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <2.6 at Week 24, 48, 96 and 144

Secondary: Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <2.6 at Week 24, 48, 96 and 144

Secondary: Percentage of participants achieving Disease Activity Score using 28 joint count and Erythrocyte Sedimentation Rate (ESR) <2.6 (DAS28-ESR Remission) at Week 24, 48, 96 and 132

Secondary: Percentage of participants achieving Disease Activity Score using 28 joint count and Erythrocyte Sedimentation Rate (ESR) <2.6 (DAS28-ESR Remission) at Week 24, 48, 96 and 132

Secondary: Percentage of participants achieving American College of Rheumatology (ACR)/ European league against rheumatism (EULAR) remission at Week 24, 48, 96 and 144

Secondary: Percentage of participants achieving American College of Rheumatology (ACR)/ European league against rheumatism (EULAR) remission at Week 24, 48, 96 and 144

Secondary: Absolute Values for Clinical Disease Activity Index (CDAI) total score

Secondary: Absolute Values for Clinical Disease Activity Index (CDAI) total score

Secondary: Absolute Values for Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP)

Secondary: Absolute Values for Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP)

Secondary: Absolute Values for Disease Activity Score using 28 joint count and Erythrocyte Sedimentation Rate (DAS28-ESR)

Secondary: Absolute Values for Disease Activity Score using 28 joint count and Erythrocyte Sedimentation Rate (DAS28-ESR)

Secondary: Absolute values for Health Assessment Questionnaire Disability Index (HAQ-DI)

Secondary: Absolute values for Health Assessment Questionnaire Disability Index (HAQ-DI)

Clinical Trial Results:
A Multi-Centre Long-term Extension Study to Assess the Safety and Efficacy of GSK3196165 in the Treatment of Rheumatoid Arthritis