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Clinical Trial Results:
A Randomized, Double-blind, Placebo- and Active-controlled, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Filgotinib Administered for 52 weeks in Combination with Methotrexate to Subjects with Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

Summary
EudraCT number	2016-000568-41
Trial protocol	SK GB BE HU CZ DE ES BG PL NL IT
Global end of trial date	20 Jun 2019

Results information
Results version number	v2(current)
This version publication date	04 Jun 2021
First version publication date	05 Jul 2020
Other versions	v1
Version creation reason	New data added to full data set Added additional secondary endpoints.

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

GS-US-417-0301

ISRCTN number

US NCT number

NCT02889796

WHO universal trial number (UTN)

Sponsor organisation name

Gilead Sciences

Sponsor organisation address

333 Lakeside Drive, Foster City, CA, United States, 94404

Public contact

Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com

Scientific contact

Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.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

20 Jun 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

04 Jul 2018

Global end of trial reached?

Yes

Global end of trial date

20 Jun 2019

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to evaluate the effects of filgotinib versus placebo for the treatment of signs and symptoms of rheumatoid arthritis (RA) as measured by the percentage of participants achieving an American College of Rheumatology 20% improvement response (ACR20) at Week 12.

Protection of trial subjects

The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.

Background therapy

Methotrexate (MTX) was used across all the arms as background therapy.

Evidence for comparator

Actual start date of recruitment

30 Aug 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Slovakia: 8

Country: Number of subjects enrolled

South Africa: 34

Country: Number of subjects enrolled

Spain: 30

Country: Number of subjects enrolled

Taiwan: 44

Country: Number of subjects enrolled

Thailand: 23

Country: Number of subjects enrolled

Ukraine: 235

Country: Number of subjects enrolled

United Kingdom: 14

Country: Number of subjects enrolled

United States: 200

Country: Number of subjects enrolled

Argentina: 57

Country: Number of subjects enrolled

Australia: 1

Country: Number of subjects enrolled

Belgium: 10

Country: Number of subjects enrolled

Bulgaria: 34

Country: Number of subjects enrolled

Canada: 12

Country: Number of subjects enrolled

Czech Republic: 34

Country: Number of subjects enrolled

Germany: 20

Country: Number of subjects enrolled

Hong Kong: 7

Country: Number of subjects enrolled

Hungary: 47

Country: Number of subjects enrolled

India: 137

Country: Number of subjects enrolled

Ireland: 1

Country: Number of subjects enrolled

Israel: 11

Country: Number of subjects enrolled

Italy: 6

Country: Number of subjects enrolled

Japan: 147

Country: Number of subjects enrolled

Korea, Democratic People's Republic of: 33

Country: Number of subjects enrolled

Mexico: 125

Country: Number of subjects enrolled

Netherlands: 2

Country: Number of subjects enrolled

New Zealand: 18

Country: Number of subjects enrolled

Poland: 299

Country: Number of subjects enrolled

Romania: 31

Country: Number of subjects enrolled

Russian Federation: 118

Country: Number of subjects enrolled

Serbia: 21

Worldwide total number of subjects

1759

EEA total number of subjects

536

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)

1425

From 65 to 84 years

333

85 years and over

Subject disposition

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Recruitment details

Participants were enrolled at study sites in Asia, South Africa, Australia, Europe, North America, South America and New Zealand. The first participant was screened on 30 August 2016. The last study visit occurred on 20 June 2019.

Screening details

2582 participants were screened. Completed in the 'Placebo never received Filgotinib' arm included participants who completed 24 weeks of placebo treatment and were not rerandomized to Filgotinib 200 mg or 100 mg groups.

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

Are arms mutually exclusive

Yes

Filgotinib 200 mg

Arm description

Participants were administered a filgotinib 200 mg tablet orally, once daily + placebo to match [PTM] filgotinib 100 mg tablet orally, once daily + PTM adalimumab 40 mg subcutaneous (SC) injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 52.1 weeks.

Arm type

Experimental

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

Other name

GS-6034, GLPG0634

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

200 mg administered once daily

Investigational medicinal product name

PTM Filgotinib 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 100 mg administered once daily

Investigational medicinal product name

PTM Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

PTM adalimumab 40 mg administered once every 2 weeks

Filgotinib 100 mg

Arm description

Participants were administered a filgotinib 100 mg tablet orally, once daily + PTM filgotinib 200 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 52.1 weeks.

Arm type

Experimental

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

Other name

GS-6034, GLPG0634

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

100 mg administered once daily

Investigational medicinal product name

PTM Filgotinib 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 200 mg administered once daily

Investigational medicinal product name

PTM Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

PTM adalimumab 40 mg administered once every 2 weeks

Adalimumab

Arm description

Participants were administered PTM filgotinib 200 mg tablet orally, once daily + PTM filgotinib 100 mg tablet orally, once daily + adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 52.1 weeks.

Arm type

Active comparator

Investigational medicinal product name

PTM Filgotinib 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 200 mg administered once daily

Investigational medicinal product name

PTM Filgotinib 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 100 mg administered once daily

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

40 mg administered once every 2 weeks

Placebo to Filgotinib 200 mg

Arm description

Participants in the placebo arm were administered a PTM filgotinib 200 mg tablet orally, once daily+ a PTM filgotinib 100 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 24 weeks. Then the participants in the placebo arm were rerandomized to filgotinib 200 mg and were administered a filgotinib 200 mg tablet orally, once daily + PTM filgotinib 100 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 28.1 weeks.

Arm type

Experimental

Investigational medicinal product name

PTM Filgotinib 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 200 mg administered once daily

Investigational medicinal product name

PTM Filgotinib 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 100 mg administered once daily

Investigational medicinal product name

PTM Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

PTM adalimumab 40 mg administered once every 2 weeks

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

Other name

GS-6034, GLPG0634

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

200 mg administered once daily

Placebo to Filgotinib 100 mg

Arm description

Participants in the placebo arm were administered a PTM filgotinib 200 mg tablet orally, once daily+ a PTM filgotinib 100 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 24 weeks. Then the participants in the placebo arm were rerandomized to filgotinib 100 mg and were administered a filgotinib 100 mg tablet orally, once daily + PTM filgotinib 200 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 28.1 weeks.

Arm type

Experimental

Investigational medicinal product name

PTM Filgotinib 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 200 mg administered once daily

Investigational medicinal product name

PTM Filgotinib 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 100 mg administered once daily

Investigational medicinal product name

PTM Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

PTM adalimumab 40 mg administered once every 2 weeks

Investigational medicinal product name

Filgotinib

Investigational medicinal product code

Other name

GS-6034, GLPG0634

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

100 mg administered once daily

Placebo never received Filgotinib

Arm description

Arm type

Placebo

Investigational medicinal product name

PTM Filgotinib 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 200 mg administered once daily

Investigational medicinal product name

PTM Filgotinib 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

PTM filgotinib 100 mg administered once daily

Investigational medicinal product name

PTM Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

PTM adalimumab 40 mg administered once every 2 weeks

Number of subjects in period 1 ^[1]	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg	Placebo never received Filgotinib
Started	475	480	325	190	191	94
Completed	424	422	281	181	185	24
Not completed	51	58	44	9	6	70
Protocol violation	-	1	3	-	-	4
Death	1	1	-	1	-	1
Pregnancy	-	1	1	-	-	-
Adverse event	17	8	8	4	1	7
Non-compliance with study drug	-	2	-	-	1	2
Investigator`s discretion	10	9	10	3	-	15
Lost to follow-up	5	7	2	-	2	6
Withdrew consent	18	29	20	1	2	35

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Four participants who were randomized but did not receive the study drug are not included in analysis.

Baseline characteristics

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Reporting group title

Overall Study

Reporting group description

Reporting group values	Overall Study	Total
Number of subjects	1755	1755
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	53.0 ( 12.7 )	-
Gender categorical
Units: Subjects
Female	1435	1435
Male	320	320
Race
For participants in Not Permitted category: local regulators did not allow collection of race information.
Units: Subjects
American Indian or Alaska Native	103	103
Asian: Japanese	147	147
Asian: Chinese/Taiwanese/Hong Kong Chinese	51	51
Asian: Korean	34	34
Asian: Other	179	179
Black or African American	35	35
Native Hawaiian or Pacific Islander	3	3
White	1184	1184
Other	17	17
Not Permitted	2	2
Ethnicity
For participants in Not Permitted category: local regulators did not allow collection of ethnicity information.
Units: Subjects
Hispanic or Latino	262	262
Not Hispanic or Latino	1471	1471
Not Permitted	22	22

Subject analysis set title

Filgotinib 200 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants were administered a filgotinib 200 mg tablet orally, once daily + a placebo to match (PTM) filgotinib 100 mg tablet orally, once daily + PTM adalimumab 40 mg subcutaneous (SC) injection, once every 2 weeks in addition to a weekly stable dose of methotrexate (MTX), orally for median exposure of 52.1 weeks.

Subject analysis set title

Filgotinib 100 mg

Subject analysis set type

Full analysis

Subject analysis set description

Participants were administered a filgotinib 100 mg tablet orally, once daily + a PTM filgotinib 200 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 52.1 weeks.

Subject analysis set title

Adalimumab

Subject analysis set type

Full analysis

Subject analysis set description

Participants were administered a PTM filgotinib 200 mg tablet orally, once daily + a PTM filgotinib 100 mg tablet orally, once daily + adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 52.1 weeks.

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

The Placebo arm included all participants who received placebo in the study. Participants were administered a PTM filgotinib 200 mg tablet orally, once daily+ a PTM filgotinib 100 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 24 weeks. Participants could be rerandomized to filgotinib 200 mg or 100 mg groups.

Subject analysis sets values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects	475	480	325	475
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	52.0 ( 12.8 )	53.0 ( 12.6 )	53.0 ( 12.9 )	53.0 ( 12.8 )
Gender categorical
Units: Subjects
Female	379	399	266	391
Male	96	81	59	84
Race
For participants in Not Permitted category: local regulators did not allow collection of race information.
Units: Subjects
American Indian or Alaska Native	27	27	20	29
Asian: Japanese	40	41	28	38
Asian: Chinese/Taiwanese/Hong Kong Chinese	13	12	8	18
Asian: Korean	13	10	4	7
Asian: Other	56	52	25	46
Black or African American	6	7	10	12
Native Hawaiian or Pacific Islander	1	0	0	2
White	312	324	229	319
Other	7	6	1	3
Not Permitted	0	1	0	1
Ethnicity
For participants in Not Permitted category: local regulators did not allow collection of ethnicity information.
Units: Subjects
Hispanic or Latino	67	71	54	70
Not Hispanic or Latino	404	399	268	400
Not Permitted	4	10	3	5

End points

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Reporting group title

Filgotinib 200 mg

Reporting group description

Reporting group title

Filgotinib 100 mg

Reporting group description

Reporting group title

Adalimumab

Reporting group description

Reporting group title

Placebo to Filgotinib 200 mg

Reporting group description

Reporting group title

Placebo to Filgotinib 100 mg

Reporting group description

Participants in the placebo arm were administered a PTM filgotinib 200 mg tablet orally, once daily+ a PTM filgotinib 100 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 24 weeks. Then the participants in the placebo arm were rerandomized to filgotinib 100 mg and were administered a filgotinib 100 mg tablet orally, once daily + PTM filgotinib 200 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 28.1 weeks.

Reporting group title

Placebo never received Filgotinib

Reporting group description

Subject analysis set title

Filgotinib 200 mg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Filgotinib 100 mg

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Adalimumab

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Placebo

Subject analysis set type

Full analysis

Subject analysis set description

Primary: Percentage of Participants who Achieved an American College of Rheumatology (ACR) 20% Improvement (ACR20) Response at Week 12

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End point title

Percentage of Participants who Achieved an American College of Rheumatology (ACR) 20% Improvement (ACR20) Response at Week 12

End point description

ACR20 response is achieved when the participant has: ≥20% improvement (reduction) from baseline in tender joint count based on 68 joints (TJC68), swollen joint count based on 66 joints (SJC66) and in at least 3 of the following 5 items: physician’s global assessment of disease activity (PGA), subject’s global assessment of disease activity (SGA) using visual analog scale (VAS) on a scale of 0 (no disease activity) to 100 (maximum disease activity),participant`s pain assessment using VAS on a scale of 0 (no pain) to 100 (unbearable pain),health assessment questionnaire disability index (HAQ-DI) score contains 20 questions,8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities scored on a scale of 0 (without difficulty) to 3 (unable to do);high-sensitivity C-reactive protein (hsCRP). Full Analysis Set included participants who were randomized and received at least 1 dose of study drug. Participants with missing outcomes were set as non-responders.

End point type

Primary

End point timeframe

Week 12

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)	76.6 (72.7 to 80.5)	69.8 (65.6 to 74.0)	70.5 (65.3 to 75.6)	49.9 (45.3 to 54.5)

Filgotinib 200 mg vs Placebo

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[1]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

26.7

Confidence interval

level

95%

sides

2-sided

lower limit

20.6

upper limit

32.8

Notes
[1] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[2]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

19.9

Confidence interval

level

95%

sides

2-sided

lower limit

13.6

upper limit

26.2

Notes
[2] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: Percentage of Participants who Achieved Disease Activity Score for 28 Joint Count Using C-Reactive Protein [DAS28 (CRP)] ≤ 3.2 at Week 12

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End point title

Percentage of Participants who Achieved Disease Activity Score for 28 Joint Count Using C-Reactive Protein [DAS28 (CRP)] ≤ 3.2 at Week 12

End point description

The DAS28 score is a measure of the participant’s disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), Patient’s Global Assessment of Disease Activity (visual analog scale: 0 = no disease activity to 100 = maximum disease activity), and hsCRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. Participants in the Full Analysis Set were analyzed. Participants with missing outcomes were set as non-responders.

End point type

Secondary

End point timeframe

Week 12

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)	49.7 (45.1 to 54.3)	38.8 (34.3 to 43.2)	43.4 (37.8 to 48.9)	23.4 (19.5 to 27.3)

Filgotinib 200 mg vs Placebo

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[3]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

26.3

Confidence interval

level

95%

sides

2-sided

lower limit

20.2

upper limit

32.4

Notes
[3] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[4]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

15.4

Confidence interval

level

95%

sides

2-sided

lower limit

9.4

upper limit

21.4

Notes
[4] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Adalimumab

Comparison groups

Filgotinib 200 mg v Adalimumab

Number of subjects included in analysis

800

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

P-value

< 0.001 ^[6]

Method

Method proposed by [Liu 2014]

Confidence interval

Notes
[5] - For non-inferiority test, the approach proposed by Liu 2014 was used to demonstrate that each filgotinib dose preserves more than 50% of the effect of adalimumab on the response rate of DAS28 (CRP) ≤ 3.2 using NRI.
[6] - P-value of non-inferiority test was calculated from approach proposed by [Liu 2014].

Filgotinib 100 mg vs Adalimumab

Comparison groups

Filgotinib 100 mg v Adalimumab

Number of subjects included in analysis

805

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

P-value

= 0.054 ^[8]

Method

Method proposed by [Liu 2014]

Confidence interval

Notes
[7] - For non-inferiority test, the approach proposed by Liu 2014 was used to demonstrate that each filgotinib dose preserves more than 50% of the effect of adalimumab on the response rate of DAS28 (CRP) ≤ 3.2 using NRI.
[8] - P-value of non-inferiority test was calculated from approach proposed by [Liu 2014].

Filgotinib 200 mg vs Adalimumab

Comparison groups

Filgotinib 200 mg v Adalimumab

Number of subjects included in analysis

800

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.069 ^[9]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

6.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

13.6

Notes
[9] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Adalimumab

Comparison groups

Filgotinib 100 mg v Adalimumab

Number of subjects included in analysis

805

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.18 ^[10]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

-4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-11.8

upper limit

2.6

Notes
[10] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

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

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End point title

Change from Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 12

End point description

The HAQ-DI score is defined as the average of the scores of eight functional categories (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities), usually completed by the participant. Responses in each functional category are collected as 0 (without any difficulty) to 3 (unable to do a task in that area), with or without aids or devices. The eight category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). When 6 or more categories are non-missing, total possible score is 3. If more than 2 categories are missing, the HAQ-DI score is set to missing. Negative change from baseline indicates improvement (less disability). Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Week 12

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Baseline	1.59 ( 0.611 )	1.55 ( 0.625 )	1.59 ( 0.600 )	1.63 ( 0.613 )
Change at Week 12 (n=457, 459, 311, 435)	-0.69 ( 0.613 )	-0.56 ( 0.564 )	-0.61 ( 0.560 )	-0.42 ( 0.544 )

Filgotinib 200 mg vs Placebo

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority ^[11]

P-value

< 0.001 ^[12]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.034

Notes
[11] - Least squares (LS)-Mean, 95% CI, and P-value were provided from mixed effects model for repeated measure (MMRM). Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.
[12] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority ^[13]

P-value

< 0.001 ^[14]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.034

Notes
[13] - LS-Mean, 95% CI, and P-value were provided from MMRM. Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.
[14] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Percentage of Participants who Achieved DAS28 (CRP) < 2.6 at Week 24

Top of page

End point title

Percentage of Participants who Achieved DAS28 (CRP) < 2.6 at Week 24

End point description

End point type

Secondary

End point timeframe

Week 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)	48.4 (43.8 to 53.0)	35.2 (30.8 to 39.6)	35.7 (30.3 to 41.1)	16.2 (12.8 to 19.6)

Filgotinib 200 mg vs Placebo

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[15]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

32.2

Confidence interval

level

95%

sides

2-sided

lower limit

26.4

upper limit

Notes
[15] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[16]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

13.4

upper limit

24.6

Notes
[16] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: Change from Baseline in Modified Total Sharp Score (mTSS) at Week 24

Top of page

End point title

Change from Baseline in Modified Total Sharp Score (mTSS) at Week 24

End point description

Participant`s radiographs of bilateral hands, wrists and feet are taken and evaluated through central review using the mTSS method. The mTSS (range [0-448]) is defined as the erosion score (range [0-280]) plus the joint space narrowing (JSN) score (range [0-168]). An erosion score of 0 to 5 is given to each joint in the hands and wrists, and a score of 0 to 10 is given to each joint in the feet where 0 indicates no erosion while 5 or 10 indicates extensive loss of bone (maximum erosion). JSN is scored from 0 to 4, with 0 indicating normal or no narrowing and 4 indicating complete loss of joint space. The maximal TSS is 448. Negative change in value indicates improvement (less erosion of bone, normal joint spaces). Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Week 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	467	471	319	466
Units: score on a scale
arithmetic mean (standard deviation)
Baseline	32.47 ( 47.939 )	36.70 ( 53.065 )	34.82 ( 55.013 )	31.60 ( 53.217 )
Change at Week 24 (n=405, 404, 271, 351)	0.13 ( 0.937 )	0.17 ( 0.905 )	0.16 ( 0.948 )	0.37 ( 1.417 )

Filgotinib 200 mg vs Placebo

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

933

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

P-value

< 0.001 ^[18]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.078

Notes
[17] - LS-Mean, 95% CI, and P-value were provided from MMRM. Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.
[18] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

937

Analysis specification

Pre-specified

Analysis type

superiority ^[19]

P-value

= 0.001 ^[20]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.078

Notes
[19] - LS-Mean, 95% CI, and P-value were provided from MMRM. Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.
[20] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Percentage of Participants who Achieved ACR 50% Improvement (ACR50) at Weeks 2, 4, 12, and 24

Top of page

End point title

Percentage of Participants who Achieved ACR 50% Improvement (ACR50) at Weeks 2, 4, 12, and 24

End point description

ACR50 response is achieved when the participant has: ≥50% improvement (reduction) from baseline in TJC68, SJC66 and in at least 3 of the following 5 items: PGA and SGA assessed using VAS on a scale of 0-100 [0 and 100 indicating no disease activity and maximum disease activity]; subject`s pain assessment using VAS on a scale of 0-100 [0 and 100 indicating no pain and unbearable pain]; HAQ-DI score contains 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities and scored on a scale of 0 (without difficulty) to 3 (unable to do); hsCRP. Participants with missing outcomes were set as non-responders. Participants in the Full Analysis Set were analyzed.

End point type

Secondary

End point timeframe

Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)
Week 2	9.1 (6.4 to 11.7)	5.8 (3.6 to 8.0)	6.8 (3.9 to 9.7)	1.1 (0.0 to 2.1)
Week 4	22.3 (18.5 to 26.2)	12.9 (9.8 to 16.0)	17.2 (13.0 to 21.5)	5.9 (3.7 to 8.1)
Week 12	47.2 (42.6 to 51.8)	36.5 (32.0 to 40.9)	35.1 (29.7 to 40.4)	19.8 (16.1 to 23.5)
Week 24	57.9 (53.3 to 62.4)	52.7 (48.1 to 57.3)	52.3 (46.7 to 57.9)	33.3 (28.9 to 37.6)

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[21]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

5.1

upper limit

10.9

Notes
[21] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[22]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

4.8

Confidence interval

level

95%

sides

2-sided

lower limit

2.3

upper limit

7.3

Notes
[22] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[23]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

16.4

Confidence interval

level

95%

sides

2-sided

lower limit

11.9

upper limit

20.9

Notes
[23] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[24]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

3.1

upper limit

10.9

Notes
[24] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 12

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[25]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

27.4

Confidence interval

level

95%

sides

2-sided

lower limit

21.4

upper limit

33.3

Notes
[25] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 12

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[26]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

16.7

Confidence interval

level

95%

sides

2-sided

lower limit

10.9

upper limit

22.5

Notes
[26] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[27]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

24.6

Confidence interval

level

95%

sides

2-sided

lower limit

18.3

upper limit

Notes
[27] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[28]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

19.4

Confidence interval

level

95%

sides

2-sided

lower limit

13.1

upper limit

25.8

Notes
[28] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: Percentage of Participants Who Achieved ACR50 at Weeks 36 and 52

Top of page

End point title

Percentage of Participants Who Achieved ACR50 at Weeks 36 and 52 ^[29]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of participants
number (confidence interval 95%)
Week 36	63.2 (58.7 to 67.6)	57.7 (53.2 to 62.2)	57.5 (52.0 to 63.1)	67.9 (61.0 to 74.8)	63.4 (56.3 to 70.4)
Week 52	64.2 (59.8 to 68.6)	60.6 (56.2 to 65.1)	62.2 (56.7 to 67.6)	68.4 (61.5 to 75.3)	66.0 (59.0 to 72.9)

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved ACR 70% Improvement (ACR70) at Weeks 2, 4, 12, and 24

Top of page

End point title

Percentage of Participants Who Achieved ACR 70% Improvement (ACR70) at Weeks 2, 4, 12, and 24

End point description

ACR70 response is achieved when the participant has: ≥70% improvement (reduction) from baseline in TJC68, SJC66 and in at least 3 of the following 5 items: PGA and SGA assessed using VAS on a scale of 0-100 [0 and 100 indicating no disease activity and maximum disease activity]; subject`s pain assessment using VAS on a scale of 0-100 [0 and 100 indicating no pain and unbearable pain]; HAQ-DI score contains 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities and scored on a scale of 0 (without difficulty) to 3 (unable to do); hsCRP. Participants with missing outcomes were set as non-responders. Participants in the Full Analysis Set were analyzed.

End point type

Secondary

End point timeframe

Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)
Week 2	2.7 (1.2 to 4.3)	1.3 (0.2 to 2.3)	0.9 (0.0 to 2.1)	0.4 (0.0 to 1.1)
Week 4	9.1 (6.4 to 11.7)	3.3 (1.6 to 5.0)	3.7 (1.5 to 5.9)	1.5 (0.3 to 2.7)
Week 12	26.1 (22.1 to 30.2)	18.5 (15.0 to 22.1)	14.2 (10.2 to 18.1)	6.7 (4.4 to 9.1)
Week 24	36.2 (31.8 to 40.6)	29.6 (25.4 to 33.8)	29.5 (24.4 to 34.7)	14.9 (11.6 to 18.3)

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008 ^[30]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

4.1

Notes
[30] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.18 ^[31]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

2.2

Notes
[31] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[32]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

7.6

Confidence interval

level

95%

sides

2-sided

lower limit

4.6

upper limit

10.6

Notes
[32] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.067 ^[33]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Notes
[33] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 12

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[34]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

19.4

Confidence interval

level

95%

sides

2-sided

lower limit

14.6

upper limit

24.1

Notes
[34] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 12

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[35]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

11.8

Confidence interval

level

95%

sides

2-sided

lower limit

7.5

upper limit

16.2

Notes
[35] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[36]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

21.3

Confidence interval

level

95%

sides

2-sided

lower limit

15.7

upper limit

26.9

Notes
[36] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[37]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

14.6

Confidence interval

level

95%

sides

2-sided

lower limit

9.2

upper limit

Notes
[37] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: Percentage of Participants Who Achieved ACR70 at Weeks 36 and 52

Top of page

End point title

Percentage of Participants Who Achieved ACR70 at Weeks 36 and 52 ^[38]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of participants
number (confidence interval 95%)
Week 36	40.2 (35.7 to 44.7)	35.4 (31.0 to 39.8)	32.9 (27.7 to 38.2)	44.7 (37.4 to 52.1)	34.6 (27.5 to 41.6)
Week 52	44.4 (39.8 to 49.0)	39.0 (34.5 to 43.4)	41.2 (35.7 to 46.7)	48.4 (41.1 to 55.8)	37.7 (30.6 to 44.8)

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved ACR20 Response at Weeks 2, 4, and 24

Top of page

End point title

Percentage of Participants Who Achieved ACR20 Response at Weeks 2, 4, and 24

End point description

ACR20 response is achieved when the participant has: ≥20% improvement (reduction) from baseline in TJC68, SJC66 and in at least 3 of the following 5 items: PGA and SGA assessed using VAS on a scale of 0-100 [0 and 100 indicating no disease activity and maximum disease activity]; subject`s pain assessment using VAS on a scale of 0-100 [0 and 100 indicating no pain and unbearable pain]; HAQ-DI score contains 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities and scored on a scale of 0 (without difficulty) to 3 (unable to do); hsCRP. Participants with missing outcomes were set as non-responders. Participants in the Full Analysis Set were analyzed.

End point type

Secondary

End point timeframe

Weeks 2, 4, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)
Week 2	37.3 (32.8 to 41.7)	27.5 (23.4 to 31.6)	33.5 (28.3 to 38.8)	14.9 (11.6 to 18.3)
Week 4	51.6 (47.0 to 56.2)	45.6 (41.1 to 50.2)	47.1 (41.5 to 52.7)	31.8 (27.5 to 36.1)
Week 24	78.1 (74.3 to 81.9)	77.7 (73.9 to 81.5)	74.5 (69.6 to 79.4)	59.2 (54.6 to 63.7)

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[39]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

22.3

Confidence interval

level

95%

sides

2-sided

lower limit

16.7

upper limit

27.9

Notes
[39] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[40]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

12.6

Confidence interval

level

95%

sides

2-sided

lower limit

7.2

upper limit

17.9

Notes
[40] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[41]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

19.8

Confidence interval

level

95%

sides

2-sided

lower limit

13.4

upper limit

26.1

Notes
[41] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[42]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

13.8

Confidence interval

level

95%

sides

2-sided

lower limit

7.5

upper limit

20.2

Notes
[42] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[43]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

24.9

Notes
[43] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[44]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

18.6

Confidence interval

level

95%

sides

2-sided

lower limit

12.6

upper limit

24.5

Notes
[44] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: Percentage of Participants Who Achieved ACR20 Response at Weeks 36 and 52

Top of page

End point title

Percentage of Participants Who Achieved ACR20 Response at Weeks 36 and 52 ^[45]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of participants
number (confidence interval 95%)
Week 36	82.9 (79.5 to 86.4)	79.2 (75.4 to 82.9)	76.3 (71.5 to 81.1)	90.5 (86.1 to 95.0)	86.9 (81.9 to 92.0)
Week 52	82.9 (79.5 to 86.4)	79.6 (75.9 to 83.3)	77.8 (73.2 to 82.5)	86.3 (81.2 to 91.5)	85.9 (80.7 to 91.1)

No statistical analyses for this end point

Secondary: Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 2, 4, and 24

Top of page

End point title

Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 2, 4, and 24

End point description

The HAQ-DI score is defined as the average of the scores of eight functional categories (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities), usually completed by the participant. Responses in each functional category are collected as 0 (without any difficulty) to 3 (unable to do a task in that area), with or without aids or devices. The eight category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Baseline	1.59 ( 0.611 )	1.55 ( 0.625 )	1.59 ( 0.600 )	1.63 ( 0.613 )
Change from Baseline at Week 2 (N=463,474,317,466)	-0.30 ( 0.443 )	-0.22 ( 0.406 )	-0.29 ( 0.440 )	-0.15 ( 0.357 )
Change from Baseline at Week 4 (N=469,471,320,461)	-0.43 ( 0.493 )	-0.33 ( 0.454 )	-0.40 ( 0.460 )	-0.26 ( 0.431 )
Change from Baseline at Week 24(N=418,423,283,376)	-0.82 ( 0.632 )	-0.75 ( 0.597 )	-0.78 ( 0.632 )	-0.62 ( 0.598 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 2; LS-Mean, 95% CI, and P-value were provided from MMRM. Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[46]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

-0.12

Variability estimate

Standard error of the mean

Dispersion value

0.025

Notes
[46] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[47]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.025

Notes
[47] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 4; LS-Mean, 95% CI, and P-value were provided from MMRM. Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[48]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

-0.13

Variability estimate

Standard error of the mean

Dispersion value

0.028

Notes
[48] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[49]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

-0.04

Variability estimate

Standard error of the mean

Dispersion value

0.028

Notes
[49] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 24; LS-Mean, 95% CI, and P-value were provided from MMRM. Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[50]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

-0.19

Variability estimate

Standard error of the mean

Dispersion value

0.037

Notes
[50] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[51]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

-0.11

Variability estimate

Standard error of the mean

Dispersion value

0.037

Notes
[51] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 36 and 52

Top of page

End point title

Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 36 and 52 ^[52]

End point description

The HAQ-DI score is defined as the average of the scores of eight functional categories (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities), usually completed by the participant. Responses in each functional category are collected as 0 (without any difficulty) to 3 (unable to do a task in that area), with or without aids or devices. The eight category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	1.59 ( 0.611 )	1.55 ( 0.625 )	1.59 ( 0.600 )	1.68 ( 0.578 )	1.58 ( 0.603 )
Change from BL at Week 36 (N=412,417,275,180,188)	-0.88 ( 0.633 )	-0.80 ( 0.611 )	-0.81 ( 0.634 )	-0.96 ( 0.637 )	-0.69 ( 0.610 )
Change from BL at Week 52 (N=400,398,265,173,177)	-0.93 ( 0.649 )	-0.85 ( 0.621 )	-0.85 ( 0.647 )	-0.99 ( 0.644 )	-0.73 ( 0.650 )

No statistical analyses for this end point

Secondary: Change From Baseline in Individual ACR Component: Tender Joint Count Based on 68 Joints (TJC68) at Weeks 2, 4, 12, and 24

Top of page

End point title

Change From Baseline in Individual ACR Component: Tender Joint Count Based on 68 Joints (TJC68) at Weeks 2, 4, 12, and 24

End point description

TJC was examined on 68 joints of the fingers, elbows, hips, knees, ankles, and toes distal for pain in response to pressure or passive motion at the study time points. Joint pain was scored as 0 = Absent; 1 = Present for each joint. The overall Tender Joint Count ranged from 0 to 68. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: tender joint count
arithmetic mean (standard deviation)
Baseline (BL)	25 ( 13.5 )	25 ( 13.4 )	24 ( 13.2 )	24 ( 13.5 )
Change from BL at Week 2 (N=464,473,317,464)	-8 ( 10.1 )	-7 ( 9.3 )	-7 ( 8.8 )	-5 ( 9.0 )
Change from BL at Week 4 (N=469,471,320,461)	-11 ( 11.1 )	-10 ( 10.3 )	-9 ( 9.2 )	-8 ( 10.5 )
Change from BL at Week 12 (N=458,458,311,435)	-17 ( 11.1 )	-15 ( 10.7 )	-15 ( 9.9 )	-13 ( 11.6 )
Change from BL at Week 24 (N=418,423,283,375)	-20 ( 12.1 )	-19 ( 10.9 )	-18 ( 11.1 )	-17 ( 11.7 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[53]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

-2

Variability estimate

Standard error of the mean

Dispersion value

0.6

Notes
[53] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01 ^[54]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.6

Notes
[54] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[55]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

-2

Variability estimate

Standard error of the mean

Dispersion value

0.6

Notes
[55] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[56]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.6

Notes
[56] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 12; LS-Mean, 95% CI, and P-value were provided from MMRM. Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[57]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

-2

Variability estimate

Standard error of the mean

Dispersion value

0.6

Notes
[57] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[58]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.6

Notes
[58] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[59]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

-2

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[59] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[60]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[60] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in Individual ACR Component: TJC68 at Weeks 36 and 52

Top of page

End point title

Change From Baseline in Individual ACR Component: TJC68 at Weeks 36 and 52 ^[61]

End point description

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: tender joint count
arithmetic mean (standard deviation)
Baseline (BL)	25 ( 13.5 )	25 ( 13.4 )	24 ( 13.2 )	25 ( 12.8 )	24 ( 12.9 )
Change from BL at Week 36 (N=411,417,275,178,188)	-21 ( 11.9 )	-20 ( 11.2 )	-19 ( 11.0 )	-21 ( 11.4 )	-19 ( 11.5 )
Change from BL at Week 52 (N=400,397,265,173,177)	-21 ( 12.2 )	-21 ( 11.4 )	-20 ( 11.4 )	-21 ( 11.9 )	-20 ( 11.2 )

No statistical analyses for this end point

Secondary: Change From Baseline in Individual ACR Component: Swollen Joint Count Based on 66 Joints (SJC66) at Weeks 2, 4, 12, and 24

Top of page

End point title

Change From Baseline in Individual ACR Component: Swollen Joint Count Based on 66 Joints (SJC66) at Weeks 2, 4, 12, and 24

End point description

The total SJC66 was based on 66 joints (same 68 joints counted in TJC68 minus hips). It was derived as the sum of all "1s" (presence of a joint swelling was scored as "1" and the absence of swelling was scored as "0," provided the joint was not replaced or could not be assessed due to other reasons) thus collected with no penalty considered for the joints not assessed or those which had been replaced. The range for SJC66 is 0 to 66. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: swollen joint count
arithmetic mean (standard deviation)
Baseline (BL)	15 ( 8.5 )	15 ( 8.5 )	16 ( 8.4 )	16 ( 8.5 )
Change from BL at Week 2 (N=464,473,317,464)	-6 ( 6.7 )	-5 ( 6.8 )	-6 ( 5.8 )	-5 ( 6.9 )
Change from BL at Week 4 (N=469,471,320,461)	-8 ( 7.1 )	-8 ( 7.8 )	-7 ( 6.6 )	-6 ( 7.8 )
Change from BL at Week 12 (N=458,458,311,435)	-11 ( 7.5 )	-11 ( 8.1 )	-11 ( 7.1 )	-10 ( 8.4 )
Change from BL at Week 24 (N=418,423,283,375)	-13 ( 7.8 )	-13 ( 7.4 )	-13 ( 6.9 )	-12 ( 7.7 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[62]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[62] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.047 ^[63]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[63] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[64]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[64] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[65]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[65] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[66]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[66] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[67]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[67] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[68]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.3

Notes
[68] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[69]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

0.3

Notes
[69] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in Individual ACR Component: SJC66 at Weeks 36 and 52

Top of page

End point title

Change From Baseline in Individual ACR Component: SJC66 at Weeks 36 and 52 ^[70]

End point description

The total SJC66 was based on 66 joints. It was derived as the sum of all "1s" (presence of a joint swelling was scored as "1" and the absence of swelling was scored as "0," provided the joint was not replaced or could not be assessed due to other reasons) thus collected with no penalty considered for the joints not assessed or those which had been replaced. The range for SJC66 is 0 to 66. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: swollen joint count
arithmetic mean (standard deviation)
Baseline (BL)	15 ( 8.5 )	15 ( 8.5 )	16 ( 8.4 )	16 ( 8.2 )	15 ( 7.9 )
Change from BL at Week 36 (N=411,417,275,178,188)	-14 ( 7.8 )	-13 ( 7.6 )	-14 ( 7.1 )	-14 ( 7.3 )	-13 ( 7.2 )
Change from BL at Week 52 (N=400,397,265,173,177)	-14 ( 8.1 )	-13 ( 7.6 )	-14 ( 7.5 )	-14 ( 7.8 )	-13 ( 7.4 )

No statistical analyses for this end point

Secondary: Change From Baseline in Individual ACR Component: Subject’s Global Assessment of Disease Activity (SGA) at Weeks 2, 4, 12, and 24

Top of page

End point title

Change From Baseline in Individual ACR Component: Subject’s Global Assessment of Disease Activity (SGA) at Weeks 2, 4, 12, and 24

End point description

SGA was assessed by the participant using a VAS on a scale of 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	67 ( 19.2 )	65 ( 19.7 )	67 ( 19.1 )	68 ( 18.7 )
Change from BL at Week 2 (N=464,474,318,466)	-16 ( 20.1 )	-11 ( 18.4 )	-13 ( 18.1 )	-8 ( 17.2 )
Change from BL at Week 4 (N=469,472,319,461)	-22 ( 21.5 )	-16 ( 20.8 )	-19 ( 20.8 )	-13 ( 20.2 )
Change from BL at Week 12 (N=457,458,311,435)	-33 ( 24.8 )	-28 ( 24.7 )	-28 ( 23.2 )	-21 ( 24.8 )
Change from BL at Week 24 (N=418,423,283,376)	-39 ( 25.8 )	-36 ( 24.9 )	-36 ( 24.9 )	-31 ( 26.9 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[71]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-9

Confidence interval

level

95%

sides

2-sided

lower limit

-11

upper limit

-7

Variability estimate

Standard error of the mean

Dispersion value

1.1

Notes
[71] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[72]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-5

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

-2

Variability estimate

Standard error of the mean

Dispersion value

1.1

Notes
[72] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[73]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-9

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

-7

Variability estimate

Standard error of the mean

Dispersion value

1.3

Notes
[73] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[74]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-5

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

-2

Variability estimate

Standard error of the mean

Dispersion value

1.3

Notes
[74] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[75]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-13

Confidence interval

level

95%

sides

2-sided

lower limit

-16

upper limit

-10

Variability estimate

Standard error of the mean

Dispersion value

1.5

Notes
[75] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[76]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-10

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

-7

Variability estimate

Standard error of the mean

Dispersion value

1.5

Notes
[76] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[77]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-11

Confidence interval

level

95%

sides

2-sided

lower limit

-14

upper limit

-7

Variability estimate

Standard error of the mean

Dispersion value

1.6

Notes
[77] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[78]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-8

Confidence interval

level

95%

sides

2-sided

lower limit

-11

upper limit

-5

Variability estimate

Standard error of the mean

Dispersion value

1.6

Notes
[78] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in Individual ACR Component: SGA at Weeks 36 and 52

Top of page

End point title

Change From Baseline in Individual ACR Component: SGA at Weeks 36 and 52 ^[79]

End point description

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	67 ( 19.2 )	65 ( 19.7 )	67 ( 19.1 )	70 ( 17.8 )	66 ( 18.7 )
Change from BL at Week 36 (N=412,417,274,180,188)	-42 ( 24.2 )	-39 ( 25.3 )	-39 ( 25.2 )	-45 ( 24.7 )	-38 ( 25.5 )
Change from BL at Week 52 (N=400,398,265,173,177)	-44 ( 24.4 )	-41 ( 25.4 )	-42 ( 25.7 )	-45 ( 27.6 )	-41 ( 25.3 )

No statistical analyses for this end point

Secondary: Change From Baseline in Individual ACR Component: Physician’s Global Assessment of Disease Activity (PGA) at Weeks 2, 4, 12, and 24

Top of page

End point title

Change From Baseline in Individual ACR Component: Physician’s Global Assessment of Disease Activity (PGA) at Weeks 2, 4, 12, and 24

End point description

PGA was assessed by the physician using a VAS on a scale of 0 (no disease activity) to 100 (maximum disease activity). A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	66 ( 16.0 )	65 ( 16.5 )	67 ( 15.5 )	66 ( 16.2 )
Change from BL at Week 2 (N=463,469,315,463)	-20 ( 19.3 )	-18 ( 18.5 )	-19 ( 17.9 )	-13 ( 17.8 )
Change from BL at Week 4 (N=468,466,318,457)	-28 ( 21.2 )	-26 ( 19.7 )	-26 ( 19.6 )	-20 ( 19.6 )
Change from BL at Week 12 (N=457,450,308,433)	-41 ( 20.2 )	-39 ( 20.3 )	-39 ( 20.4 )	-34 ( 22.4 )
Change from BL at Week 24 (N=413,419,283,373)	-48 ( 19.2 )	-46 ( 19.6 )	-47 ( 19.4 )	-42 ( 20.4 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[80]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-8

Confidence interval

level

95%

sides

2-sided

lower limit

-10

upper limit

-6

Variability estimate

Standard error of the mean

Dispersion value

1.1

Notes
[80] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[81]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

-4

Variability estimate

Standard error of the mean

Dispersion value

1.1

Notes
[81] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[82]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-8

Confidence interval

level

95%

sides

2-sided

lower limit

-11

upper limit

-6

Variability estimate

Standard error of the mean

Dispersion value

1.2

Notes
[82] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[83]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-9

upper limit

-5

Variability estimate

Standard error of the mean

Dispersion value

1.2

Notes
[83] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[84]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-8

Confidence interval

level

95%

sides

2-sided

lower limit

-10

upper limit

-6

Variability estimate

Standard error of the mean

Dispersion value

1.2

Notes
[84] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[85]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-10

upper limit

-5

Variability estimate

Standard error of the mean

Dispersion value

1.2

Notes
[85] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[86]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-8

Confidence interval

level

95%

sides

2-sided

lower limit

-11

upper limit

-6

Variability estimate

Standard error of the mean

Dispersion value

1.1

Notes
[86] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[87]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-7

Confidence interval

level

95%

sides

2-sided

lower limit

-10

upper limit

-5

Variability estimate

Standard error of the mean

Dispersion value

1.1

Notes
[87] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in Individual ACR Component: PGA at Weeks 36 and 52

Top of page

End point title

Change From Baseline in Individual ACR Component: PGA at Weeks 36 and 52 ^[88]

End point description

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	66 ( 16.0 )	65 ( 16.5 )	67 ( 15.5 )	68 ( 15.6 )	64 ( 16.3 )
Change from BL at Week 36 (N=409,416,273,176,187)	-51 ( 19.0 )	-49 ( 19.8 )	-50 ( 18.6 )	-53 ( 19.5 )	-47 ( 20.0 )
Change from BL at Week 52 (N=400,398,265,173,177)	-53 ( 18.2 )	-50 ( 19.2 )	-52 ( 18.9 )	-54 ( 19.7 )	-50 ( 19.3 )

No statistical analyses for this end point

Secondary: Change From Baseline in Individual ACR Component: Subject`s Pain Assessment at Weeks 2, 4, 12, and 24

Top of page

End point title

Change From Baseline in Individual ACR Component: Subject`s Pain Assessment at Weeks 2, 4, 12, and 24

End point description

The participant assessed their pain severity using a VAS on a scale of 0 (no pain) to 100 (severe pain). A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	65 ( 20.4 )	64 ( 20.1 )	64 ( 19.5 )	66 ( 19.0 )
Change from BL at Week 2 (N=463,474,317,466)	-16 ( 21.0 )	-12 ( 18.7 )	-13 ( 20.4 )	-7 ( 18.2 )
Change from BL at Week 4 (N=469,471,319,461)	-21 ( 23.7 )	-18 ( 20.9 )	-18 ( 21.9 )	-12 ( 20.8 )
Change from BL at Week 12 (N=457,458,311,435)	-31 ( 26.9 )	-29 ( 25.3 )	-27 ( 23.6 )	-21 ( 26.0 )
Change from BL at Week 24 (N=418,423,283,376)	-38 ( 27.0 )	-37 ( 25.6 )	-35 ( 24.2 )	-30 ( 27.0 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[89]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-9

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

-7

Variability estimate

Standard error of the mean

Dispersion value

1.2

Notes
[89] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[90]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

-3

Variability estimate

Standard error of the mean

Dispersion value

1.2

Notes
[90] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[91]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-9

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

-7

Variability estimate

Standard error of the mean

Dispersion value

1.3

Notes
[91] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[92]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-9

upper limit

-4

Variability estimate

Standard error of the mean

Dispersion value

1.3

Notes
[92] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[93]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-12

Confidence interval

level

95%

sides

2-sided

lower limit

-15

upper limit

-9

Variability estimate

Standard error of the mean

Dispersion value

1.5

Notes
[93] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[94]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-10

Confidence interval

level

95%

sides

2-sided

lower limit

-13

upper limit

-7

Variability estimate

Standard error of the mean

Dispersion value

1.5

Notes
[94] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[95]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-11

Confidence interval

level

95%

sides

2-sided

lower limit

-14

upper limit

-7

Variability estimate

Standard error of the mean

Dispersion value

1.6

Notes
[95] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[96]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-9

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

-6

Variability estimate

Standard error of the mean

Dispersion value

1.6

Notes
[96] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in Individual ACR Component: Subject`s Pain Assessment at Weeks 36 and 52

Top of page

End point title

Change From Baseline in Individual ACR Component: Subject`s Pain Assessment at Weeks 36 and 52 ^[97]

End point description

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	65 ( 20.4 )	64 ( 20.1 )	64 ( 19.5 )	68 ( 18.0 )	65 ( 19.2 )
Change from BL at Week 36 (N=412,417,274,180,188)	-40 ( 26.3 )	-38 ( 26.2 )	-37 ( 25.5 )	-44 ( 24.9 )	-39 ( 25.9 )
Change from BL at Week 52 (N=400,398,265,173,177)	-43 ( 26.2 )	-41 ( 25.9 )	-41 ( 25.6 )	-45 ( 26.6 )	-41 ( 25.6 )

No statistical analyses for this end point

Secondary: Change From Baseline in Individual ACR Component: High-Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 12, and 24

Top of page

End point title

Change From Baseline in Individual ACR Component: High-Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 12, and 24

End point description

Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: mg/L
arithmetic mean (standard deviation)
Baseline (BL)	16.13 ( 21.005 )	16.74 ( 22.982 )	14.56 ( 18.003 )	16.25 ( 24.051 )
Change from BL at Week 2 (N=455,467,315,463)	-10.85 ( 20.154 )	-7.67 ( 17.888 )	-8.03 ( 15.594 )	-0.07 ( 17.244 )
Change from BL at Week 4 (N=465,468,319,456)	-9.99 ( 21.146 )	-8.44 ( 20.201 )	-7.17 ( 16.896 )	-1.12 ( 19.940 )
Change from BL at Week 12 (N=456,454,308,431)	-11.00 ( 18.659 )	-9.55 ( 21.330 )	-7.85 ( 20.632 )	-3.26 ( 22.711 )
Change from BL at Week 24 (N=416,419,281,370)	-11.84 ( 20.693 )	-10.54 ( 22.215 )	-6.17 ( 24.224 )	-4.00 ( 19.614 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[98]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-10.83

Confidence interval

level

95%

sides

2-sided

lower limit

-12.7

upper limit

-8.96

Variability estimate

Standard error of the mean

Dispersion value

0.952

Notes
[98] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[99]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-7.73

Confidence interval

level

95%

sides

2-sided

lower limit

-9.58

upper limit

-5.87

Variability estimate

Standard error of the mean

Dispersion value

0.947

Notes
[99] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[100]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-9.39

Confidence interval

level

95%

sides

2-sided

lower limit

-11.33

upper limit

-7.45

Variability estimate

Standard error of the mean

Dispersion value

0.989

Notes
[100] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[101]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-7.35

Confidence interval

level

95%

sides

2-sided

lower limit

-9.29

upper limit

-5.42

Variability estimate

Standard error of the mean

Dispersion value

0.987

Notes
[101] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[102]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-8.02

Confidence interval

level

95%

sides

2-sided

lower limit

-9.9

upper limit

-6.13

Variability estimate

Standard error of the mean

Dispersion value

0.961

Notes
[102] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[103]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-6.46

Confidence interval

level

95%

sides

2-sided

lower limit

-8.35

upper limit

-4.58

Variability estimate

Standard error of the mean

Dispersion value

0.96

Notes
[103] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[104]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-7.91

Confidence interval

level

95%

sides

2-sided

lower limit

-9.88

upper limit

-5.93

Variability estimate

Standard error of the mean

Dispersion value

1.007

Notes
[104] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[105]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-6.59

Confidence interval

level

95%

sides

2-sided

lower limit

-8.56

upper limit

-4.62

Variability estimate

Standard error of the mean

Dispersion value

1.005

Notes
[105] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in Individual ACR Component: hsCRP at Weeks 36 and 52

Top of page

End point title

Change From Baseline in Individual ACR Component: hsCRP at Weeks 36 and 52 ^[106]

End point description

Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[106] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: mg/L
arithmetic mean (standard deviation)
Baseline (BL)	16.13 ( 21.005 )	16.74 ( 22.982 )	14.56 ( 18.003 )	16.54 ( 24.782 )	15.76 ( 21.871 )
Change from BL at Week 36 (N=408,413,273,179,184)	-11.51 ( 21.990 )	-10.72 ( 22.569 )	-8.73 ( 18.214 )	-12.12 ( 23.151 )	-8.50 ( 19.749 )
Change from BL at Week 52 (N=396,386,259,169,171)	-12.19 ( 20.773 )	-11.27 ( 23.129 )	-9.60 ( 16.511 )	-11.43 ( 20.873 )	-8.74 ( 19.921 )

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved an Improvement (Decrease) in the HAQ-DI Score ≥ 0.22 at Weeks 2, 4, 12, and 24

Top of page

End point title

Percentage of Participants Who Achieved an Improvement (Decrease) in the HAQ-DI Score ≥ 0.22 at Weeks 2, 4, 12, and 24

End point description

The HAQ-DI score is defined as the average of the scores of eight functional categories (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities), usually completed by the participant. Responses in each functional category are collected as 0 (without any difficulty) to 3 (unable to do a task in that area), with or without aids or devices. The eight category scores are averaged into an overall HAQ-DI score on a scale from 0-3 [0 (no disability) to 3 (completely disabled) when 6 or more categories are non-missing, so total possible score is 3. Improvement is defined as reduction in HAQ-DI, (baseline value - postbaseline value) ≥ 0.22. If more than 2 categories are missing, the HAQ-DI score is set to missing. Participants with missing outcomes were set as non-responders. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)
Week 2 (N=459,467,316,463)	52.5 (47.8 to 57.2)	46.7 (42.0 to 51.3)	51.9 (46.2 to 57.6)	40.2 (35.6 to 44.7)
Week 4 (N=459,467,316,463)	66.2 (61.8 to 70.7)	58.0 (53.4 to 62.6)	63.9 (58.5 to 69.4)	49.9 (45.2 to 54.6)
Week 12 (N=459,467,316,463)	78.9 (75.0 to 82.7)	71.5 (67.3 to 75.7)	72.8 (67.6 to 77.9)	57.9 (53.3 to 62.5)
Week 24 (N=459,467,316,463)	76.0 (72.0 to 80.0)	73.4 (69.3 to 77.6)	71.2 (66.1 to 76.4)	59.4 (54.8 to 64.0)

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[107]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

12.3

Confidence interval

level

95%

sides

2-sided

lower limit

5.7

upper limit

18.9

Notes
[107] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.043 ^[108]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

6.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

13.1

Notes
[108] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[109]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

16.3

Confidence interval

level

95%

sides

2-sided

lower limit

9.8

upper limit

22.8

Notes
[109] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011 ^[110]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

14.7

Notes
[110] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 12

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[111]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

14.9

upper limit

Notes
[111] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 12

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[112]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

13.6

Confidence interval

level

95%

sides

2-sided

lower limit

7.3

upper limit

19.9

Notes
[112] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[113]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

16.6

Confidence interval

level

95%

sides

2-sided

lower limit

10.5

upper limit

22.8

Notes
[113] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[114]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

14.1

Confidence interval

level

95%

sides

2-sided

lower limit

7.8

upper limit

20.3

Notes
[114] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: Percentage of Participants Who Achieved an Improvement (Decrease) in the HAQ-DI Score ≥ 0.22 at Weeks 36 and 52

Top of page

End point title

Percentage of Participants Who Achieved an Improvement (Decrease) in the HAQ-DI Score ≥ 0.22 at Weeks 36 and 52 ^[115]

End point description

The HAQ-DI score is defined as the average of the scores of eight functional categories (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities), usually completed by the participant. Responses in each functional category are collected as 0 (without any difficulty) to 3 (unable to do a task in that area), with or without aids or devices. The eight category scores are averaged into an overall HAQ-DI score on a scale from 0-3 [0 (no disability) to 3 (completely disabled) when 6 or more categories are non-missing, so total possible score is 3. Improvement is defined as reduction in HAQ-DI, (baseline value - postbaseline value) ≥ 0.22. If more than 2 categories are missing, the HAQ-DI score is set to missing. Participants with missing outcomes were set as non-responders. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[115] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of participants
number (confidence interval 95%)
Week 36 (N=459,467,316,185,188)	77.1 (73.2 to 81.1)	74.9 (70.9 to 79.0)	71.5 (66.4 to 76.7)	83.2 (77.6 to 88.9)	77.7 (71.4 to 83.9)
Week 52 (N=459,467,316,185,188)	75.8 (71.8 to 79.8)	73.0 (68.9 to 77.2)	70.3 (65.1 to 75.5)	81.6 (75.8 to 87.5)	71.8 (65.1 to 78.5)

No statistical analyses for this end point

Secondary: Change From Baseline in DAS28 (CRP) at Weeks 2, 4, 12, and 24

Top of page

End point title

Change From Baseline in DAS28 (CRP) at Weeks 2, 4, 12, and 24

End point description

The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), SGA (VAS: 0 = no disease activity to 100 = maximum disease activity), and hsCRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Baseline	5.8 ( 0.88 )	5.7 ( 0.95 )	5.7 ( 0.88 )	5.7 ( 0.91 )
Change from Baseline at Week 2 (N=452,464,314,461)	-1.3 ( 1.05 )	-1.0 ( 0.90 )	-1.1 ( 0.90 )	-0.6 ( 0.79 )
Change from Baseline at Week 4 (N=463,467,318,454)	-1.7 ( 1.19 )	-1.4 ( 1.07 )	-1.4 ( 1.04 )	-0.9 ( 0.98 )
Change from Baseline at Week 12(N=455,452,308,431)	-2.5 ( 1.24 )	-2.2 ( 1.17 )	-2.2 ( 1.12 )	-1.6 ( 1.19 )
Change from Baseline at Week 24(N=415,419,281,368)	-3.1 ( 1.17 )	-2.8 ( 1.08 )	-2.7 ( 1.20 )	-2.2 ( 1.20 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[116]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

-0.6

Variability estimate

Standard error of the mean

Dispersion value

0.06

Notes
[116] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[117]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

-0.3

Variability estimate

Standard error of the mean

Dispersion value

0.06

Notes
[117] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[118]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

-0.7

Variability estimate

Standard error of the mean

Dispersion value

0.07

Notes
[118] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[119]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.4

Variability estimate

Standard error of the mean

Dispersion value

0.07

Notes
[119] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[120]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

-0.8

Variability estimate

Standard error of the mean

Dispersion value

0.07

Notes
[120] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[121]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.07

Notes
[121] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[122]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

-0.8

Variability estimate

Standard error of the mean

Dispersion value

0.08

Notes
[122] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[123]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.08

Notes
[123] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in DAS28 (CRP) at Weeks 36 and 52

Top of page

End point title

Change From Baseline in DAS28 (CRP) at Weeks 36 and 52 ^[124]

End point description

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[124] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	5.8 ( 0.88 )	5.7 ( 0.95 )	5.7 ( 0.88 )	5.9 ( 0.89 )	5.6 ( 0.89 )
Change from BL at Week 36 (N=407,413,272,177,184)	-3.2 ( 1.09 )	-2.9 ( 1.17 )	-2.9 ( 1.16 )	-3.3 ( 1.10 )	-2.8 ( 1.08 )
Change from BL at Week 52 (N=393,385,259,169,171)	-3.4 ( 1.11 )	-3.1 ( 1.09 )	-3.1 ( 1.13 )	-3.3 ( 1.16 )	-3.0 ( 1.04 )

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 2, 4, and 24

Top of page

End point title

Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 2, 4, and 24

End point description

The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), SGA (VAS: 0 = no disease activity to 100 = maximum disease activity), and hsCRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. Participants with missing outcomes were set as non-responders. Participants in the Full Analysis Set were analyzed.

End point type

Secondary

End point timeframe

Weeks 2, 4, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)
Week 2	13.1 (9.9 to 16.2)	8.1 (5.6 to 10.7)	9.8 (6.5 to 13.2)	3.6 (1.8 to 5.4)
Week 4	25.5 (21.5 to 29.5)	20.4 (16.7 to 24.1)	20.9 (16.3 to 25.5)	9.3 (6.6 to 12.0)
Week 24	60.6 (56.1 to 65.1)	53.1 (48.6 to 57.7)	50.5 (44.9 to 56.1)	33.7 (29.3 to 38.0)

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[125]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

9.5

Confidence interval

level

95%

sides

2-sided

lower limit

5.8

upper limit

13.1

Notes
[125] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[126]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

4.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

7.7

Notes
[126] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[127]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

11.3

upper limit

21.1

Notes
[127] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[128]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

11.2

Confidence interval

level

95%

sides

2-sided

lower limit

6.5

upper limit

15.8

Notes
[128] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[129]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

26.9

Confidence interval

level

95%

sides

2-sided

lower limit

20.6

upper limit

33.3

Notes
[129] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 24

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[130]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

19.4

Confidence interval

level

95%

sides

2-sided

lower limit

13.1

upper limit

25.8

Notes
[130] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 36 and 52

Top of page

End point title

Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 36 and 52 ^[131]

End point description

The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), SGA (VAS: 0 = no disease activity to 100 = maximum disease activity), and hsCRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. Participants with missing outcomes were set as non-responders. Participants in the Full Analysis Set were analyzed.

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[131] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of participants
number (confidence interval 95%)
Week 36	67.4 (63.0 to 71.7)	60.2 (55.7 to 64.7)	58.2 (52.6 to 63.7)	74.7 (68.3 to 81.2)	66.5 (59.5 to 73.4)
Week 52	68.2 (63.9 to 72.5)	62.1 (57.6 to 66.5)	61.8 (56.4 to 67.3)	69.5 (62.7 to 76.3)	67.5 (60.6 to 74.4)

No statistical analyses for this end point

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) < 2.6 at Weeks 2, 4, and 12

Top of page

End point title

Percentage of Participants Who Achieved DAS28 (CRP) < 2.6 at Weeks 2, 4, and 12

End point description

The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), SGA (VAS: 0 = no disease activity to 100 = maximum disease activity), and hsCRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. Participants with missing outcomes were set as non-responders. Participants in the Full Analysis Set were analyzed.

End point type

Secondary

End point timeframe

Weeks 2, 4, and 12

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)
Week 2	5.1 (3.0 to 7.1)	1.7 (0.4 to 2.9)	3.4 (1.3 to 5.5)	0.6 (0.0 to 1.4)
Week 4	13.7 (10.5 to 16.9)	8.8 (6.1 to 11.4)	8.0 (4.9 to 11.1)	2.9 (1.3 to 4.6)
Week 12	34.1 (29.7 to 38.5)	23.8 (19.8 to 27.7)	23.7 (18.9 to 28.5)	9.3 (6.6 to 12.0)

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[132]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

4.4

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

6.7

Notes
[132] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 2

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.17 ^[133]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

2.6

Notes
[133] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[134]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

10.7

Confidence interval

level

95%

sides

2-sided

lower limit

7.1

upper limit

14.4

Notes
[134] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 4

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[135]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

Notes
[135] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Week 12

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[136]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

24.8

Confidence interval

level

95%

sides

2-sided

lower limit

19.6

upper limit

Notes
[136] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Week 12

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[137]

Method

Regression, Logistic

Parameter type

Difference in Response Rates

Point estimate

14.5

Confidence interval

level

95%

sides

2-sided

lower limit

9.7

upper limit

19.3

Notes
[137] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) < 2.6 at Weeks 36 and 52

Top of page

End point title

Percentage of Participants Who Achieved DAS28 (CRP) < 2.6 at Weeks 36 and 52 ^[138]

End point description

The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), SGA (VAS: 0 = no disease activity to 100 = maximum disease activity), and hsCRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. Participants with missing outcomes were set as non-responders. Participants in the Full Analysis Set were analyzed.

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[138] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of participants
number (confidence interval 95%)
Week 36	50.3 (45.7 to 54.9)	42.9 (38.4 to 47.4)	42.5 (36.9 to 48.0)	52.1 (44.7 to 59.5)	46.1 (38.7 to 53.4)
Week 52	54.5 (49.9 to 59.1)	44.8 (40.2 to 49.3)	48.6 (43.0 to 54.2)	50.5 (43.2 to 57.9)	50.8 (43.4 to 58.1)

No statistical analyses for this end point

Secondary: American College of Rheumatology N Percent Improvement (ACR-N) at Weeks 2, 4, 12, and 24

Top of page

End point title

American College of Rheumatology N Percent Improvement (ACR-N) at Weeks 2, 4, 12, and 24

End point description

ACR-N is defined as the smallest percentage improvement from baseline in swollen joints, tender joints and the median of the following 5 items (PGA, SGA, subject`s pain assessment, HAQ-DI and hsCRP). It has a range between 0 and 100%. PGA and SGA assessed using VAS on a scale of 0-100 [0 and 100 indicating no disease activity and maximum disease activity]; subject`s pain assessment using VAS on a scale of 0-100 [0 and 100 indicating no pain and unbearable pain]; HAQ-DI score contains 20 questions,8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities and scored on a scale of 0 (without difficulty) to 3 (unable to do). If this calculation results in a negative value, then the ACR-N is set to 0. The ACR-N value indicates an improvement of N%, with higher numbers indicating greater improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percent improvement
arithmetic mean (standard deviation)
Week 2 (N=441,451,306,450)	18.3 ( 19.98 )	14.0 ( 17.14 )	16.3 ( 18.41 )	8.0 ( 12.82 )
Week 4 (N=453,453,311,443)	27.4 ( 25.24 )	23.0 ( 22.26 )	23.8 ( 22.94 )	15.1 ( 18.92 )
Week 12 (N=445,436,300,422)	46.8 ( 28.46 )	40.6 ( 27.32 )	40.4 ( 26.18 )	28.1 ( 25.22 )
Week 24 (N=402,408,276,360)	58.8 ( 27.76 )	55.4 ( 26.47 )	54.3 ( 28.13 )	42.6 ( 27.73 )

No statistical analyses for this end point

Secondary: ACR N Percent Improvement (ACR-N) at Weeks 36 and 52

Top of page

End point title

ACR N Percent Improvement (ACR-N) at Weeks 36 and 52 ^[139]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[139] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percent improvement
arithmetic mean (standard deviation)
Week 36 (N=397,406,267,171,181)	62.5 ( 26.01 )	59.1 ( 27.47 )	58.6 ( 27.17 )	63.2 ( 24.59 )	56.1 ( 27.30 )
Week 52 (N=385,379,255,165,170)	66.0 ( 25.89 )	63.1 ( 26.34 )	63.5 ( 27.03 )	63.8 ( 28.00 )	59.7 ( 26.81 )

No statistical analyses for this end point

Secondary: Number of Participants With European League Against Rheumatism (EULAR) Response at Weeks 2, 4, 12, and 24

Top of page

End point title

Number of Participants With European League Against Rheumatism (EULAR) Response at Weeks 2, 4, 12, and 24

End point description

Good Response: DAS28(CRP) at visit ≤3.2 and improvement from baseline >1.2. Moderate Response: DAS28(CRP) at visit ≤3.2 and improvement from baseline >0.6 and ≤1.2; DAS28(CRP) at visit >3.2 and ≤5.1 and improvement from baseline >0.6; DAS 28(CRP) at visit >5.1 and improvement from baseline >1.2. No Response: DAS28(CRP) at visit ≤5.1 and improvement from baseline ≤0.6; DAS 28(CRP) >5.1 at visit and improvement from baseline ≤1.2. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: participants
Week 2: Good Response (N=452,464,314,461)	58	32	27	15
Week 2: Moderate Response (N=452,464,314,461)	237	213	158	133
Week 2: No Response (N=452,464,314,461)	157	219	129	313
Week 4: Good Response (N=463,467,318,454)	117	86	61	37
Week 4: Moderate Response (N=463,467,318,454)	231	242	156	189
Week 4: No Response (N=463,467,318,454)	115	139	101	228
Week 12: Good Response (N=455,452,308,431)	234	177	138	106
Week 12: Moderate Response (N=455,452,308,431)	188	225	138	224
Week 12: No Response (N=455,452,308,431)	33	50	32	101
Week 24: Good Response (N=415,419,281,368)	284	250	163	154
Week 24: Moderate Response (N=415,419,281,368)	124	156	97	170
Week 24: No Response (N=415,419,281,368)	7	13	21	44

No statistical analyses for this end point

Secondary: Number of Participants With EULAR Response at Weeks 36 and 52

Top of page

End point title

Number of Participants With EULAR Response at Weeks 36 and 52 ^[140]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[140] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: participants
Week 36: Good Response (N=407,413,272,177,184)	306	276	180	139	124
Week 36: Moderate Response (N=407,413,272,177,184)	99	126	84	38	54
Week 36: No Response (N=407,413,272,177,184)	2	11	8	0	6
Week 52: Good Response (N=393,385,259,169,171)	308	282	189	129	126
Week 52: Moderate Response (N=393,385,259,169,171)	82	98	66	38	42
Week 52: No Response (N=393,385,259,169,171)	3	5	4	2	3

No statistical analyses for this end point

Secondary: Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 12, and 24

Top of page

End point title

Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 12, and 24

End point description

CDAI is calculated using formula: CDAI = TJC based on 28 joints (TJC28) + SJC based on 28 joints (SJC28) + SGA + PGA. PGA and SGA are assessed using a VAS on a scale of 0-10 [0 and 10 indicating no disease activity and maximum disease activity]. CDAI can range from 0 to 76, with higher score indicating more severe disease activity status. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	39.5 ( 11.85 )	38.6 ( 12.23 )	39.2 ( 11.51 )	39.6 ( 11.66 )
Change from BL at Week 2 (N=463,469,315,461)	-12.7 ( 11.86 )	-10.7 ( 11.17 )	-11.7 ( 10.06 )	-8.2 ( 10.10 )
Change from BL at Week 4 (N=468,466,317,457)	-17.6 ( 12.66 )	-15.6 ( 12.07 )	-15.4 ( 11.13 )	-12.4 ( 11.79 )
Change from BL at Week 12 (N=456,449,308,433)	-26.0 ( 12.41 )	-23.3 ( 12.32 )	-23.5 ( 11.43 )	-20.3 ( 13.30 )
Change from BL at Week 24 (N=413,419,283,373)	-30.6 ( 11.88 )	-28.6 ( 11.57 )	-28.4 ( 11.45 )	-26.3 ( 12.38 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[141]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

-3.2

Variability estimate

Standard error of the mean

Dispersion value

0.68

Notes
[141] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[142]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

-1.6

Variability estimate

Standard error of the mean

Dispersion value

0.68

Notes
[142] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[143]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-6.6

upper limit

-3.8

Variability estimate

Standard error of the mean

Dispersion value

0.73

Notes
[143] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[144]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

-2.4

Variability estimate

Standard error of the mean

Dispersion value

0.73

Notes
[144] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[145]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-5.9

Confidence interval

level

95%

sides

2-sided

lower limit

-7.3

upper limit

-4.6

Variability estimate

Standard error of the mean

Dispersion value

0.69

Notes
[145] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[146]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-4.4

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

-3.1

Variability estimate

Standard error of the mean

Dispersion value

0.69

Notes
[146] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[147]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-5.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.9

upper limit

-4.5

Variability estimate

Standard error of the mean

Dispersion value

0.62

Notes
[147] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[148]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

-2.9

Variability estimate

Standard error of the mean

Dispersion value

0.62

Notes
[148] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in CDAI at Weeks 36 and 52

Top of page

End point title

Change From Baseline in CDAI at Weeks 36 and 52 ^[149]

End point description

CDAI is calculated using formula: CDAI = TJC28 + SJC28 + SGA + PGA. PGA and SGA are assessed using a VAS on a scale of 0-10 [0 and 10 indicating no disease activity and maximum disease activity]. CDAI can range from 0 to 76, with higher score indicating more severe disease activity status. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[149] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	39.5 ( 11.85 )	38.6 ( 12.23 )	39.2 ( 11.51 )	41.4 ( 11.03 )	37.8 ( 11.23 )
Change from BL at Week 36 (N=409,416,273,176,187)	-32.1 ( 11.60 )	-29.9 ( 12.18 )	-30.4 ( 11.21 )	-33.8 ( 11.15 )	-29.0 ( 11.02 )
Change from BL at Week 52 (N=399,397,265,173,177)	-32.9 ( 11.69 )	-30.9 ( 11.70 )	-31.6 ( 11.44 )	-34.0 ( 11.20 )	-30.7 ( 10.80 )

No statistical analyses for this end point

Secondary: Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 12, and 24

Top of page

End point title

Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 12, and 24

End point description

SDAI is a composite measure that sums the TJC28, SJC28, SGA, PGA, and the hsCRP (in mg/dL). PGA and SGA assessed using VAS on a scale of 0-10 [0 and 10 indicating no disease activity and maximum disease activity]. Higher score indicates more severe disease activity status and total possible score is 0 to 86. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 2, 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	41.2 ( 12.26 )	40.2 ( 12.79 )	40.6 ( 11.88 )	41.2 ( 12.37 )
Change from BL at Week 2 (N=451,460,312,458)	-14.0 ( 12.19 )	-11.4 ( 11.41 )	-12.5 ( 10.52 )	-8.2 ( 10.38 )
Change from BL at Week 4 (N=462,462,316,450)	-18.6 ( 13.08 )	-16.4 ( 12.31 )	-16.1 ( 11.47 )	-12.5 ( 12.18 )
Change from BL at Week 12 (N=454,444,305,429)	-27.1 ( 12.69 )	-24.1 ( 12.54 )	-24.3 ( 12.03 )	-20.6 ( 13.85 )
Change from BL at Week 24 (N=410,415,281,366)	-31.8 ( 12.18 )	-29.7 ( 12.01 )	-29.0 ( 12.19 )	-26.6 ( 12.91 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[150]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-5.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

-4.4

Variability estimate

Standard error of the mean

Dispersion value

0.7

Notes
[150] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[151]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-3.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

-2.2

Variability estimate

Standard error of the mean

Dispersion value

0.7

Notes
[151] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[152]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-6.1

Confidence interval

level

95%

sides

2-sided

lower limit

-7.6

upper limit

-4.6

Variability estimate

Standard error of the mean

Dispersion value

0.75

Notes
[152] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[153]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

-3.1

Variability estimate

Standard error of the mean

Dispersion value

0.75

Notes
[153] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[154]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-6.8

Confidence interval

level

95%

sides

2-sided

lower limit

-8.2

upper limit

-5.4

Variability estimate

Standard error of the mean

Dispersion value

0.71

Notes
[154] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[155]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-5.1

Confidence interval

level

95%

sides

2-sided

lower limit

-6.5

upper limit

-3.7

Variability estimate

Standard error of the mean

Dispersion value

0.71

Notes
[155] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[156]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-6.5

Confidence interval

level

95%

sides

2-sided

lower limit

-7.8

upper limit

-5.3

Variability estimate

Standard error of the mean

Dispersion value

0.65

Notes
[156] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[157]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

-3.5

Variability estimate

Standard error of the mean

Dispersion value

0.65

Notes
[157] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in SDAI at Weeks 36 and 52

Top of page

End point title

Change From Baseline in SDAI at Weeks 36 and 52 ^[158]

End point description

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[158] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	41.2 ( 12.26 )	40.2 ( 12.79 )	40.6 ( 11.88 )	43.0 ( 11.81 )	39.4 ( 11.81 )
Change from BL at Week 36 (N=405,412,271,175,183)	-33.3 ( 11.92 )	-31.0 ( 12.69 )	-31.2 ( 11.73 )	-35.1 ( 11.83 )	-29.9 ( 11.40 )
Change from BL at Week 52 (N=393,385,259,169,171)	-34.1 ( 12.15 )	-32.0 ( 12.25 )	-32.6 ( 11.99 )	-34.9 ( 11.83 )	-31.6 ( 11.11 )

No statistical analyses for this end point

Secondary: Change From Baseline in mTSS at Week 52

Top of page

End point title

Change From Baseline in mTSS at Week 52 ^[159]

End point description

End point type

Secondary

End point timeframe

Baseline; Week 52

Notes
[159] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	468	472	319	187	188
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	32.62 ( 48.306 )	36.24 ( 52.956 )	33.94 ( 53.803 )	26.68 ( 45.870 )	32.38 ( 55.012 )
Change from BL at Week 52 (N=417,411,273,180,178)	0.21 ( 1.434 )	0.50 ( 2.098 )	0.58 ( 3.621 )	0.63 ( 2.782 )	0.90 ( 3.152 )

Filgotinib 200 mg vs Placebo to Filgotinib 200 mg

Statistical analysis description

LS-Mean, 95% CI, and P-value were provided from MMRM. Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.

Comparison groups

Placebo to Filgotinib 200 mg v Filgotinib 200 mg

Number of subjects included in analysis

655

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.042 ^[160]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

-0.01

Notes
[160] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo to Filgotinib 100 mg

Statistical analysis description

LS-Mean, 95% CI, and P-value were provided from MMRM. Missing change scores were not imputed using the MMRM approach assuming an unstructured variance-covariance matrix for the repeated measures.

Comparison groups

Filgotinib 100 mg v Placebo to Filgotinib 100 mg

Number of subjects included in analysis

660

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.039 ^[161]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

-0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

-0.02

Notes
[161] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Percentage of Participants With no Radiographic Progression From Baseline at Week 24

Top of page

End point title

Percentage of Participants With no Radiographic Progression From Baseline at Week 24

End point description

Participant`s radiographs of bilateral hands, wrists and feet are taken and evaluated through central review using the mTSS method. No radiographic progression is defined by the change from baseline in mTSS and is reported for the following categories: Change in mTSS ≤ 0.5, Change in mTSS ≤ 0 and Change in mTSS ≤ smallest detectable change (SDC). Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of participants
number (confidence interval 95%)
Change in mTSS ≤ 0.5 (N=405,404,271,351)	93.8 (91.4 to 96.3)	91.1 (88.2 to 94.0)	91.9 (88.4 to 95.3)	87.2 (83.5 to 90.8)
Change in mTSS ≤ 0 (N=405,404,271,351)	87.9 (84.6 to 91.2)	85.9 (82.4 to 89.4)	86.3 (82.1 to 90.6)	80.9 (76.7 to 85.2)
Change in mTSS ≤ SDC (1.36) (N=405,404,271,351)	95.8 (93.7 to 97.9)	95.0 (92.8 to 97.3)	94.5 (91.6 to 97.4)	90.3 (87.1 to 93.6)

Filgotinib 200 mg vs Placebo

Statistical analysis description

Change in mTSS ≤ 0.5.

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[162]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

6.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

11.1

Notes
[162] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Change in mTSS ≤ 0.5.

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.073 ^[163]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

8.6

Notes
[163] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Change in mTSS ≤ 0.

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009 ^[164]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

12.5

Notes
[164] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Change in mTSS ≤ 0.

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.061 ^[165]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

10.6

Notes
[165] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Change in mTSS ≤ SDC (1.36).

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

950

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004 ^[166]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

5.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.6

upper limit

9.4

Notes
[166] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Change in mTSS ≤ SDC (1.36).

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

955

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.012 ^[167]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

8.8

Notes
[167] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: Percentage of Participants With no Radiographic Progression From Baseline at Week 52

Top of page

End point title

Percentage of Participants With no Radiographic Progression From Baseline at Week 52 ^[168]

End point description

End point type

Secondary

End point timeframe

Baseline; Week 52

Notes
[168] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of participants
number (confidence interval 95%)
Change in mTSS ≤ 0.5 (N=417,411,273,180,178)	92.1 (89.4 to 94.8)	87.1 (83.7 to 90.5)	88.6 (84.7 to 92.6)	83.9 (78.2 to 89.5)	83.7 (78.0 to 89.4)
Change in mTSS ≤ 0 (N=417,411,273,180,178)	87.5 (84.2 to 90.8)	81.3 (77.4 to 85.2)	82.4 (77.7 to 87.1)	73.3 (66.6 to 80.1)	77.0 (70.5 to 83.4)
Change in mTSS ≤ SDC(1.83) (N=417,411,273,180,178)	95.0 (92.7 to 97.2)	91.5 (88.7 to 94.3)	94.1 (91.2 to 97.1)	90.0 (85.3 to 94.7)	87.6 (82.5 to 92.8)

Filgotinib 200 mg vs Placebo to Filgotinib 200 mg

Statistical analysis description

Change in mTSS ≤ 0.5

Comparison groups

Filgotinib 200 mg v Placebo to Filgotinib 200 mg

Number of subjects included in analysis

665

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[169]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

8.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

14.6

Notes
[169] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo to Filgotinib 100 mg

Statistical analysis description

Change in mTSS ≤ 0.5

Comparison groups

Filgotinib 100 mg v Placebo to Filgotinib 100 mg

Number of subjects included in analysis

671

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.26 ^[170]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

10.1

Notes
[170] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo to Filgotinib 200 mg

Statistical analysis description

Change in mTSS ≤ 0

Comparison groups

Filgotinib 200 mg v Placebo to Filgotinib 200 mg

Number of subjects included in analysis

665

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[171]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

14.2

Confidence interval

level

95%

sides

2-sided

lower limit

6.6

upper limit

21.8

Notes
[171] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo to Filgotinib 100 mg

Statistical analysis description

Change in mTSS ≤ 0

Comparison groups

Filgotinib 100 mg v Placebo to Filgotinib 100 mg

Number of subjects included in analysis

671

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.22 ^[172]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

11.9

Notes
[172] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 200 mg vs Placebo to Filgotinib 200 mg

Statistical analysis description

Change in mTSS ≤ SDC (1.36)

Comparison groups

Filgotinib 200 mg v Placebo to Filgotinib 200 mg

Number of subjects included in analysis

665

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027 ^[173]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

10.2

Notes
[173] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Filgotinib 100 mg vs Placebo to Filgotinib 100 mg

Statistical analysis description

Change in mTSS ≤ SDC (1.36)

Comparison groups

Filgotinib 100 mg v Placebo to Filgotinib 100 mg

Number of subjects included in analysis

671

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.12 ^[174]

Method

Regression, Logistic

Parameter type

Difference in non-progression rate

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

9.8

Notes
[174] - P-value was calculated from the logistic regression with treatment groups and stratification factors in the model.

Secondary: 36-Item Short Form Survey (SF-36) Physical Component Summary (PCS) Score at Weeks 4, 12, and 24

Top of page

End point title

36-Item Short Form Survey (SF-36) Physical Component Summary (PCS) Score at Weeks 4, 12, and 24

End point description

The SF-36 is a 36-item, self-reported, generic, comprehensive, and health-related quality of life questionnaire based on 8 health domains in 2 components: physical well-being (physical functioning, role-physical, bodily pain, general health perceptions), mental well-being (vitality, social functioning, role-emotional, and mental health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with highest possible score of 100. Higher scores indicate better health status or functioning. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Week 4 (N=471,475,321,465)	39.0 ( 8.22 )	38.2 ( 8.35 )	37.7 ( 8.07 )	36.1 ( 7.40 )
Week 12 (N=461,464,312,441)	42.7 ( 8.30 )	42.1 ( 8.69 )	41.3 ( 8.57 )	38.8 ( 7.83 )
Week 24 (N=426,427,285,376)	43.9 ( 8.49 )	43.7 ( 8.64 )	43.2 ( 8.95 )	40.7 ( 8.10 )

No statistical analyses for this end point

Secondary: SF-36 PCS Score at Weeks 36 and 52

Top of page

End point title

SF-36 PCS Score at Weeks 36 and 52 ^[175]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[175] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Week 36 (N=413,417,276,181,188)	45.2 ( 8.28 )	44.4 ( 8.54 )	43.8 ( 8.84 )	45.2 ( 7.99 )	43.2 ( 8.82 )
Week 52 (N=400,399,267,174,180)	45.6 ( 8.35 )	45.1 ( 8.57 )	45.2 ( 8.55 )	45.1 ( 8.26 )	44.1 ( 8.88 )

No statistical analyses for this end point

Secondary: Change From Baseline in SF-36 PCS Score at Weeks 4, 12, and 24

Top of page

End point title

Change From Baseline in SF-36 PCS Score at Weeks 4, 12, and 24

End point description

The SF-36 is a 36-item, self-reported, generic, comprehensive, and health-related quality of life questionnaire based on 8 health domains in 2 components: physical well-being (physical functioning, role-physical, bodily pain, general health perceptions), mental well-being (vitality, social functioning, role-emotional, and mental health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with highest possible score of 100. Higher scores indicate better health status or functioning. Positive change in value indicates improvement and better quality of life. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	473	479	323	474
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	33.4 ( 7.17 )	33.6 ( 7.75 )	32.8 ( 7.74 )	32.9 ( 7.11 )
Change from BL at Week 4 (N=469,474,319,464)	5.6 ( 6.57 )	4.6 ( 6.50 )	5.0 ( 6.65 )	3.1 ( 6.32 )
Change from BL at Week 12 (N=459,463,310,440)	9.2 ( 8.10 )	8.5 ( 7.72 )	8.4 ( 7.89 )	5.8 ( 7.10 )
Change from BL at Week 24 (N=424,426,283,376)	10.4 ( 8.49 )	10.3 ( 8.64 )	10.4 ( 8.47 )	7.7 ( 7.97 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

947

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[176]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

1.9

upper limit

3.4

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[176] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

953

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[177]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

2.5

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[177] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

947

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[178]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

3.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.8

upper limit

4.6

Variability estimate

Standard error of the mean

Dispersion value

0.47

Notes
[178] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

953

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[179]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

3.1

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.46

Notes
[179] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

947

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[180]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

3.1

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

4.1

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[180] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

953

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[181]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

3.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

4.1

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[181] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in SF-36 PCS Score at Weeks 36 and 52

Top of page

End point title

Change From Baseline in SF-36 PCS Score at Weeks 36 and 52 ^[182]

End point description

The SF-36 is a 36-item, self-reported, generic, comprehensive, and health-related quality of life questionnaire based on 8 health domains in 2 components: physical well-being (physical functioning, role-physical, bodily pain, general health perceptions), mental well-being (vitality, social functioning, role-emotional, and mental health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with highest possible score of 100. Higher scores indicate better health status or functioning. Positive change in value indicates improvement and better quality of life. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[182] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	473	479	323	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	33.4 ( 7.17 )	33.6 ( 7.75 )	32.8 ( 7.74 )	32.2 ( 6.96 )	33.7 ( 6.96 )
Change from BL at Week 36 (N=412,416,274,181,188)	11.6 ( 8.28 )	11.0 ( 8.53 )	11.1 ( 9.07 )	12.9 ( 8.92 )	9.5 ( 8.13 )
Change from BL at Week 52 (N=399,398,265,174,180)	12.0 ( 8.73 )	11.5 ( 8.74 )	12.4 ( 9.21 )	13.0 ( 9.58 )	10.4 ( 8.05 )

No statistical analyses for this end point

Secondary: SF-36 Mental Component Summary (MCS) Score at Weeks 4, 12, and 24

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End point title

SF-36 Mental Component Summary (MCS) Score at Weeks 4, 12, and 24

End point description

End point type

Secondary

End point timeframe

Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Week 4 (N=471,475,321,465)	47.8 ( 9.90 )	47.9 ( 9.63 )	47.9 ( 10.04 )	45.8 ( 10.35 )
Week 12 (N=460,464,312,441)	49.3 ( 9.14 )	49.9 ( 8.90 )	48.9 ( 10.28 )	47.7 ( 10.16 )
Week 24 (N=426,427,285,376)	50.0 ( 8.82 )	50.2 ( 8.93 )	49.3 ( 10.26 )	49.2 ( 9.90 )

No statistical analyses for this end point

Secondary: SF-36 MCS Score at Weeks 36 and 52

Top of page

End point title

SF-36 MCS Score at Weeks 36 and 52 ^[183]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[183] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Week 36 (N=413,417,276,181,188)	50.1 ( 8.96 )	51.3 ( 8.88 )	50.7 ( 9.67 )	50.7 ( 9.04 )	50.3 ( 9.47 )
Week 52 (N=400,399,267,174,180)	50.6 ( 9.30 )	51.5 ( 8.99 )	50.8 ( 9.51 )	50.8 ( 8.55 )	50.1 ( 9.21 )

No statistical analyses for this end point

Secondary: Change From Baseline in SF-36 MCS Score at Weeks 4, 12, and 24

Top of page

End point title

Change From Baseline in SF-36 MCS Score at Weeks 4, 12, and 24

End point description

The SF-36 is a 36-item, self-reported, generic, comprehensive, and health-related quality of life questionnaire based on 8 health domains in 2 components: physical well-being (physical functioning, role-physical, bodily pain, general health perceptions), mental well-being (vitality, social functioning, role-emotional, and mental health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with highest possible score of 100. Higher scores indicate better health status or functioning. Positive change in value indicates improvement and better quality of life. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	473	479	323	474
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	43.9 ( 10.44 )	44.6 ( 10.44 )	44.1 ( 10.44 )	43.4 ( 11.01 )
Change from BL at Week 4 (N=469,474,319,464)	3.9 ( 7.96 )	3.4 ( 8.35 )	3.7 ( 7.66 )	2.3 ( 8.72 )
Change from BL at Week 12 (N=458,463,310,440)	5.4 ( 9.45 )	5.4 ( 8.97 )	4.9 ( 9.69 )	4.1 ( 9.50 )
Change from BL at Week 24 (N=424,426,283,376)	6.1 ( 9.23 )	5.7 ( 9.57 )	5.3 ( 9.25 )	5.6 ( 10.28 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

947

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[184]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

2.8

Variability estimate

Standard error of the mean

Dispersion value

0.48

Notes
[184] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

953

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[185]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.6

upper limit

2.5

Variability estimate

Standard error of the mean

Dispersion value

0.48

Notes
[185] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

947

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[186]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

2.5

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[186] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

953

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001 ^[187]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

2.7

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[187] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

947

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.086 ^[188]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.55

Notes
[188] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

953

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.12 ^[189]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

1.9

Variability estimate

Standard error of the mean

Dispersion value

0.55

Notes
[189] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in SF-36 MCS Score at Weeks 36 and 52

Top of page

End point title

Change From Baseline in SF-36 MCS Score at Weeks 36 and 52 ^[190]

End point description

The SF-36 is a 36-item, self-reported, generic, comprehensive, and health-related quality of life questionnaire based on 8 health domains in 2 components: physical well-being (physical functioning, role-physical, bodily pain, general health perceptions), mental well-being (vitality, social functioning, role-emotional, and mental health). Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with highest possible score of 100. Higher scores indicate better health status or functioning. Positive change in value indicates improvement and better quality of life. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[190] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	473	479	323	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	43.9 ( 10.44 )	44.6 ( 10.44 )	44.1 ( 10.44 )	43.9 ( 11.06 )	43.4 ( 11.03 )
Change from BL at Week 36 (N=412,416,274,181,188)	6.2 ( 10.03 )	6.6 ( 10.46 )	6.6 ( 9.40 )	6.9 ( 12.05 )	6.8 ( 9.84 )
Change from BL at Week 52 (N=399,398,265,174,180)	6.7 ( 10.53 )	6.9 ( 10.61 )	6.7 ( 9.90 )	7.2 ( 11.31 )	6.5 ( 10.35 )

No statistical analyses for this end point

Secondary: Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 4, 12, and 24

Top of page

End point title

Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 4, 12, and 24

End point description

FACIT-Fatigue scale is a brief, 13-item, symptom-specific questionnaire that specifically assesses the self-reported severity of fatigue and its impact upon daily activities and functioning in the past 7 days. The FACIT-Fatigue uses 0 (not at all) to 4 (very much) numeric rating scales for a total possible score of 0 to 52. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Week 4 (N=468,471,319,457)	33.9 ( 10.32 )	33.3 ( 9.76 )	32.9 ( 10.11 )	30.9 ( 10.43 )
Week 12 (N=455,457,307,437)	36.8 ( 9.64 )	36.7 ( 9.67 )	36.1 ( 9.68 )	33.9 ( 10.32 )
Week 24 (N=416,419,277,372)	38.5 ( 9.17 )	38.5 ( 8.74 )	37.6 ( 9.82 )	35.8 ( 9.94 )

No statistical analyses for this end point

Secondary: FACIT-Fatigue Score at Weeks 36 and 52

Top of page

End point title

FACIT-Fatigue Score at Weeks 36 and 52 ^[191]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[191] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Week 36 (N=395,405,270,177,184)	38.9 ( 8.84 )	39.5 ( 8.73 )	38.6 ( 9.45 )	39.6 ( 8.78 )	37.4 ( 9.88 )
Week 52 (N=386,379,257,167,174)	39.8 ( 8.64 )	39.8 ( 8.54 )	38.9 ( 9.87 )	39.4 ( 8.78 )	38.0 ( 9.77 )

No statistical analyses for this end point

Secondary: Change From Baseline in FACIT-Fatigue Score at Weeks 4, 12, and 24

Top of page

End point title

Change From Baseline in FACIT-Fatigue Score at Weeks 4, 12, and 24

End point description

FACIT-Fatigue scale is a brief, 13-item, symptom-specific questionnaire that specifically assesses the self-reported severity of fatigue and its impact upon daily activities and functioning in the past 7 days. The FACIT-Fatigue uses 0 (not at all) to 4 (very much) numeric rating scales for a total possible score of 0 to 52. Positive change in value indicates improvement (no or less severity of fatigue). Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	472	477	319	469
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	27.6 ( 10.68 )	27.8 ( 10.60 )	27.2 ( 10.20 )	26.9 ( 10.34 )
Change from BL at Week 4 (N=465,470,316,455)	6.3 ( 8.59 )	5.7 ( 8.77 )	5.7 ( 8.47 )	3.8 ( 8.76 )
Change from BL at Week 12 (N=452,455,304,432)	9.2 ( 9.82 )	9.1 ( 10.15 )	8.8 ( 9.19 )	6.8 ( 9.89 )
Change from BL at Week 24 (N=413,417,273,369)	10.5 ( 10.63 )	10.8 ( 10.77 )	10.3 ( 9.67 )	8.4 ( 10.48 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[192]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

3.8

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[192] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

946

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[193]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

3.2

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[193] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[194]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

3.9

Variability estimate

Standard error of the mean

Dispersion value

0.56

Notes
[194] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

946

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[195]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

3.7

Variability estimate

Standard error of the mean

Dispersion value

0.55

Notes
[195] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[196]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

3.8

Variability estimate

Standard error of the mean

Dispersion value

0.59

Notes
[196] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

946

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[197]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.6

upper limit

3.9

Variability estimate

Standard error of the mean

Dispersion value

0.59

Notes
[197] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in FACIT-Fatigue Score at Weeks 36 and 52

Top of page

End point title

Change From Baseline in FACIT-Fatigue Score at Weeks 36 and 52 ^[198]

End point description

FACIT-Fatigue scale is a brief, 13-item, symptom-specific questionnaire that specifically assesses the self-reported severity of fatigue and its impact upon daily activities and functioning in the past 7 days. The FACIT-Fatigue uses 0 (not at all) to 4 (very much) numeric rating scales for a total possible score of 0 to 52. Positive change in value indicates improvement (no or less severity of fatigue). Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[198] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	472	477	319	189	189
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	27.6 ( 10.68 )	27.8 ( 10.60 )	27.2 ( 10.20 )	26.8 ( 10.13 )	27.9 ( 10.56 )
Change from BL at Week 36 (N=393,403,268,176,182)	11.0 ( 10.22 )	11.7 ( 10.90 )	11.3 ( 10.18 )	12.8 ( 10.76 )	9.5 ( 10.25 )
Change from BL at Week 52 (N=384,376,254,166,172)	11.9 ( 10.21 )	12.2 ( 10.88 )	11.7 ( 10.79 )	12.9 ( 11.55 )	10.1 ( 10.06 )

No statistical analyses for this end point

Secondary: Number of Participants by European Quality of Life 5 Dimensions (EQ-5D) Health Profile Categories at Weeks 4, 12, and 24

Top of page

End point title

Number of Participants by European Quality of Life 5 Dimensions (EQ-5D) Health Profile Categories at Weeks 4, 12, and 24

End point description

The EQ-5D-5 levels (EQ-5D-5L) is a standardized measure of health status of the participant at the visit (same day) that provides a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of 2 components: a descriptive system of the participant`s health and a rating of his or her current health state on a 0-100 VAS. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities (Usu Act), pain/discomfort (Pai/Disc), and anxiety/depression (Anx/Dep). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Rating gets recorded on a vertical VAS in which the endpoints are labelled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks (Wk) 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: participants
Mobility: Wk4: No Problems (N=468,471,319,457)	130	129	84	100
Mobility: Wk4: Slight Problems (N=468,471,319,457)	176	173	107	149
Mobility:Wk4:Moderate Problems (N=468,471,319,457)	113	122	96	150
Mobility: Wk4: Severe Problems (N=468,471,319,457)	44	46	31	56
Mobility: Wk4:Extreme Problems (N=468,471,319,457)	5	1	1	2
Mobility: Wk12: No Problems (N=455,457,307,437)	178	177	116	132
Mobility: Wk12:Slight Problems (N=455,457,307,437)	153	151	103	154
Mobility:Wk12:Moderate Problems(N=455,457,307,437)	99	97	67	112
Mobility:Wk12:Severe Problems (N=455,457,307,437)	21	31	21	38
Mobility:Wk12:Extreme Problems (N=455,457,307,437)	4	1	0	1
Mobility: Wk24: No Problems (N=416,419,277,372)	182	189	117	131
Mobility: Wk24:Slight Problems (N=416,419,277,372)	142	136	90	126
Mobility:Wk24:Moderate Problems(N=416,419,277,372)	68	75	57	89
Mobility:Wk24:Severe Problems (N=416,419,277,372)	19	17	12	24
Mobility:Wk24:Extreme Problems (N=416,419,277,372)	5	2	1	2
Selfcare: Wk4: No Problems (N=468,471,319,457)	177	163	111	138
Selfcare: Wk4: Slight Problems (N=468,471,319,457)	180	183	120	164
Selfcare:Wk4:Moderate Problems (N=468,471,319,457)	86	103	74	124
Selfcare: Wk4: Severe Problems (N=468,471,319,457)	23	20	13	25
Selfcare: Wk4:Extreme Problems (N=468,471,319,457)	2	2	1	6
Selfcare: Wk12: No Problems (N=455,457,307,437)	243	222	147	165
Selfcare: Wk12:Slight Problems (N=455,457,307,437)	149	150	102	159
Selfcare:Wk12:Moderate Problems(N=455,457,307,437)	53	74	49	88
Selfcare: Wk12:Severe Problems (N=455,457,307,437)	8	9	9	21
Selfcare:Wk12:Extreme Problems (N=455,457,307,437)	2	2	0	4
Selfcare: Wk24: No Problems (N=416,419,277,372)	255	249	157	164
Selfcare: Wk24:Slight Problems (N=416,419,277,372)	109	121	75	140
Selfcare:Wk24:Moderate Problems(N=416,419,277,372)	45	39	36	54
Selfcare: Wk24:Severe Problems (N=416,419,277,372)	4	8	7	14
Selfcare:Wk24:Extreme Problems (N=416,419,277,372)	3	2	2	0
Usu Act: Wk4: No Problems (N=468,471,319,457)	110	102	69	65
Usu Act: Wk4: Slight Problems (N=468,471,319,457)	203	193	133	195
Usu Act: Wk4:Moderate Problems (N=468,471,319,457)	111	142	90	143
Usu Act: Wk4: Severe Problems (N=468,471,319,457)	38	33	25	52
Usu Act: Wk4: Extreme Problems (N=468,471,319,457)	6	1	2	2
Usu Act: Wk12: No Problems (N=455,457,307,437)	157	149	97	103
Usu Act: Wk12: Slight Problems (N=455,457,307,437)	200	191	130	184
Usu Act:Wk12:Moderate Problems (N=455,457,307,437)	80	90	67	116
Usu Act: Wk12: Severe Problems (N=455,457,307,437)	16	23	13	32
Usu Act: Wk12:Extreme Problems (N=455,457,307,437)	2	4	0	2
Usu Act: Wk24: No Problems (N=416,419,277,372)	184	175	109	107
Usu Act: Wk24: Slight Problems (N=416,419,277,372)	164	171	105	163
Usu Act:Wk24:Moderate Problems (N=416,419,277,372)	54	63	52	86
Usu Act: Wk24: Severe Problems (N=416,419,277,372)	13	9	9	15
Usu Act: Wk24:Extreme Problems (N=416,419,277,372)	1	1	2	1
Pain/Disc: Wk4: No Problems (N=468,471,319,457)	42	38	26	14
Pain/Disc: Wk4:Slight Problems (N=468,471,319,457)	215	185	118	157
Pain/Disc:Wk4:Moderate Problems(N=468,471,319,457)	154	204	127	198
Pain/Disc: Wk4:Severe Problems (N=468,471,319,457)	51	41	47	80
Pain/Disc:Wk4:Extreme Problems (N=468,471,319,457)	6	3	1	8
Pain/Disc: Wk12: No Problems (N=455,457,307,437)	58	71	34	29
Pain/Disc:Wk12:Slight Problems (N=455,457,307,437)	260	217	145	200
Pain/Disc:Wk12:Moderate Problem(N=455,457,307,437)	117	150	106	154
Pain/Disc:Wk12:Severe Problems (N=455,457,307,437)	20	17	22	51
Pain/Disc:Wk12:Extreme Problems(N=455,457,307,437)	0	2	0	3
Pain/Disc: Wk24: No Problems (N=416,419,277,372)	82	78	56	39
Pain/Disc:Wk24:Slight Problems (N=416,419,277,372)	226	224	127	196
Pain/Disc:Wk24:Moderate Problem(N=416,419,277,372)	86	103	82	110
Pain/Disc:Wk24:Severe Problems (N=416,419,277,372)	21	13	12	27
Pain/Disc:Wk24:Extreme Problems(N=416,419,277,372)	1	1	0	0
Anx/Dep: Wk4: No Problems (N=468,471,319,457)	211	224	151	196
Anx/Dep: Wk4: Slight Problems (N=468,471,319,457)	163	158	111	149
Anx/Dep: Wk4:Moderate Problems (N=468,471,319,457)	72	81	44	86
Anx/Dep: Wk4: Severe Problems (N=468,471,319,457)	21	8	13	25
Anx/Dep: Wk4: Extreme Problems (N=468,471,319,457)	1	0	0	1
Anx/Dep: Wk12: No Problems (N=455,457,307,437)	235	246	152	216
Anx/Dep: Wk12: Slight Problems (N=455,457,307,437)	154	143	106	137
Anx/Dep:Wk12:Moderate Problems (N=455,457,307,437)	54	63	44	62
Anx/Dep: Wk12: Severe Problems (N=455,457,307,437)	12	5	4	19
Anx/Dep: Wk12:Extreme Problems (N=455,457,307,437)	0	0	1	3
Anx/Dep: Wk24: No Problems (N=416,419,277,372)	230	256	160	204
Anx/Dep: Wk24: Slight Problems (N=416,419,277,372)	136	119	75	120
Anx/Dep:Wk24:Moderate Problems (N=416,419,277,372)	42	37	33	39
Anx/Dep: Wk24: Severe Problems (N=416,419,277,372)	8	5	6	8
Anx/Dep: Wk24:Extreme Problems (N=416,419,277,372)	0	2	3	1

No statistical analyses for this end point

Secondary: Number of Participants by EQ-5D Health Profile Categories at Weeks 36 and 52

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End point title

Number of Participants by EQ-5D Health Profile Categories at Weeks 36 and 52 ^[199]

End point description

The EQ-5D-5 levels (EQ-5D-5L) is a standardized measure of health status of the participant at the visit (same day) that provides a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of 2 components: a descriptive system of the participant`s health and a rating of his or her current health state on a 0-100 VAS. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities (Usu Act), pain/discomfort (Pai/Disc), and anxiety/depression (Anx/Dep). Each dimension has 5 levels: no problems, slight problems (Sli), moderate (Mod) problems, severe (Sev) problems, and extreme (Extre) problems. Rating gets recorded on a vertical VAS in which the endpoints are labelled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks (Wk) 36 and 52

Notes
[199] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: participants
Mobility:Wk36:No Problems(N=395,405,270,177,184)	202	189	122	86	78
Mobility:Wk36:Sli Problems(N=395,405,270,177,184)	121	136	82	58	67
Mobility:Wk36:Mod Problems(N=395,405,270,177,184)	58	64	48	26	28
Mobility:Wk36:Sev Problems(N=395,405,270,177,184)	13	15	16	7	11
Mobility:Wk36:Extre Problem(N=395,405,270,177,184)	1	1	2	0	0
Mobility:Wk52:No Problems(N=386,379,257,167,174)	197	187	130	82	77
Mobility:Wk52:Sli Problems(N=386,379,257,167,174)	117	115	79	47	61
Mobility:Wk52:Mod Problems(N=386,379,257,167,174)	57	58	38	34	27
Mobility:Wk52:Sev Problems(N=386,379,257,167,174)	11	19	10	3	8
Mobility:Wk52:Extre Problem(N=386,379,257,167,174)	4	0	0	1	1
Selfcare:Wk36:No Problems (N=395,405,270,177,184)	254	249	164	114	108
Selfcare:Wk36:Sli Problems (N=395,405,270,177,184)	104	113	67	45	46
Selfcare:Wk36:Mod Problems (N=395,405,270,177,184)	31	36	30	17	25
Selfcare:Wk36:Sev Problems (N=395,405,270,177,184)	5	5	6	1	5
Selfcare:Wk36:Extre Problem(N=395,405,270,177,184)	1	2	3	0	0
Selfcare:Wk52:No Problems (N=386,379,257,167,174)	251	245	159	105	101
Selfcare:Wk52:Sli Problems (N=386,379,257,167,174)	98	102	72	44	48
Selfcare:Wk52:Mod Problems (N=386,379,257,167,174)	30	25	24	16	18
Selfcare:Wk52:Sev Problems (N=386,379,257,167,174)	5	6	2	1	6
Selfcare:Wk52:Extre Problem(N=386,379,257,167,174)	2	1	0	1	1
Usu Act:Wk36:No Problems (N=395,405,270,177,184)	176	172	125	82	72
Usu Act:Wk36:Sli Problems (N=395,405,270,177,184)	160	171	90	71	70
Usu Act:Wk36:Mod Problems (N=395,405,270,177,184)	50	52	46	21	36
Usu Act:Wk36:Sev Problems (N=395,405,270,177,184)	7	9	7	3	5
Usu Act:Wk36:Extre Problems(N=395,405,270,177,184)	2	1	2	0	1
Usu Act:Wk52:No Problems (N=386,379,257,167,174)	183	177	121	75	71
Usu Act:Wk52:Sli Problems (N=386,379,257,167,174)	151	147	87	64	72
Usu Act:Wk52:Mod Problems (N=386,379,257,167,174)	40	41	42	22	19
Usu Act:Wk52:Sev Problems (N=386,379,257,167,174)	8	12	6	5	12
Usu Act:Wk52:Extre Problems(N=386,379,257,167,174)	4	2	1	1	0
Pain/Disc:Wk36:No Problems (N=395,405,270,177,184)	95	84	55	47	35
Pain/Disc:Wk36:Sli Problems(N=395,405,270,177,184)	206	220	127	94	97
Pain/Disc:Wk36:Mod Problems(N=395,405,270,177,184)	81	89	79	34	45
Pain/Disc:Wk36:Sev Problems(N=395,405,270,177,184)	13	11	8	2	7
Pain/Disc:Wk36:ExtreProblem(N=395,405,270,177,184)	0	1	1	0	0
Pain/Disc:Wk52:No Problems (N=386,379,257,167,174)	90	88	57	45	44
Pain/Disc:Wk52:Sli Problems(N=386,379,257,167,174)	209	210	130	80	93
Pain/Disc:Wk52:Mod Problems(N=386,379,257,167,174)	77	72	61	38	31
Pain/Disc:Wk52:Sev Problems(N=386,379,257,167,174)	10	9	9	3	6
Pain/Disc:Wk52:ExtreProblem(N=386,379,257,167,174)	0	0	0	1	0
Anx/Dep:Wk36:No Problems (N=395,405,270,177,184)	230	259	162	115	112
Anx/Dep:Wk36:Sli Problems (N=395,405,270,177,184)	123	113	79	44	51
Anx/Dep:Wk36:Mod Problems (N=395,405,270,177,184)	37	27	19	18	16
Anx/Dep:Wk36:Sev Problems (N=395,405,270,177,184)	4	5	7	0	5
Anx/Dep:Wk36:Extre Problems(N=395,405,270,177,184)	1	1	3	0	0
Anx/Dep:Wk52:No Problems (N=386,379,257,167,174)	227	254	169	111	110
Anx/Dep:Wk52:Sli Problems (N=386,379,257,167,174)	106	86	61	38	41
Anx/Dep:Wk52:Mod Problems (N=386,379,257,167,174)	48	34	23	17	19
Anx/Dep:Wk52:Sev Problems (N=386,379,257,167,174)	5	5	4	0	4
Anx/Dep:Wk52:Extre Problems(N=386,379,257,167,174)	0	0	0	1	0

No statistical analyses for this end point

Secondary: EQ-5D Current Health VAS at Weeks 4, 12, and 24

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End point title

EQ-5D Current Health VAS at Weeks 4, 12, and 24

End point description

EQ-5D-5L is a standardized measure of health status of the participant at the visit (same day) that provides a simple, generic measure of health for clinical and economic appraisal. Participant rates their current health state on a 0-100 VAS. It gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: score on a scale
arithmetic mean (standard deviation)
Week 4 (N=468,471,319,457)	59 ( 20.5 )	59 ( 19.9 )	60 ( 20.4 )	56 ( 19.5 )
Week 12 (N=455,457,307,437)	66 ( 20.3 )	66 ( 20.3 )	65 ( 19.6 )	59 ( 20.7 )
Week 24 (N=416,419,277,372)	67 ( 23.1 )	69 ( 21.6 )	68 ( 22.2 )	64 ( 21.4 )

No statistical analyses for this end point

Secondary: EQ-5D Current Health VAS at Weeks 36 and 52

Top of page

End point title

EQ-5D Current Health VAS at Weeks 36 and 52 ^[200]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[200] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: score on a scale
arithmetic mean (standard deviation)
Week 36 (N=395,405,270,177,184)	69 ( 22.7 )	72 ( 21.2 )	67 ( 24.3 )	73 ( 19.9 )	71 ( 21.1 )
Week 52 (N=386,379,257,167,174)	72 ( 21.3 )	73 ( 21.0 )	71 ( 22.5 )	73 ( 20.6 )	70 ( 22.8 )

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D Current Health VAS at Weeks 4, 12, and 24

Top of page

End point title

Change From Baseline in EQ-5D Current Health VAS at Weeks 4, 12, and 24

End point description

The EQ-5D-5L is a standardized measure of health status of the participant at the visit (same day) that provides a simple, generic measure of health for clinical and economic appraisal. Participant rates their current health state on a 0-100 VAS. It gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health. Positive change indicates improvement (better health). Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	472	477	319	469
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	48 ( 22.5 )	49 ( 22.8 )	47 ( 21.8 )	46 ( 21.8 )
Change from BL at Week 4 (N=465,470,316,455)	11 ( 24.4 )	10 ( 25.2 )	13 ( 24.4 )	10 ( 25.1 )
Change from BL at Week 12 (N=452,455,304,432)	18 ( 26.3 )	17 ( 27.4 )	17 ( 27.1 )	13 ( 26.5 )
Change from BL at Week 24 (N=413,417,273,369)	19 ( 30.5 )	21 ( 28.9 )	21 ( 28.8 )	18 ( 29.3 )

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.049 ^[201]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.2

Notes
[201] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

946

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.069 ^[202]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.2

Notes
[202] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[203]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.3

Notes
[203] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

946

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[204]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.3

Notes
[204] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 200 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 200 mg v Placebo

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.06 ^[205]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.5

Notes
[205] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Filgotinib 100 mg vs Placebo

Statistical analysis description

Comparison groups

Filgotinib 100 mg v Placebo

Number of subjects included in analysis

946

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003 ^[206]

Method

MMRM

Parameter type

Least Squares Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.5

Notes
[206] - MMRM model included treatment, visit, treatment by visit, stratification factors, and baseline value as fixed effects, and participants being the random effect.

Secondary: Change From Baseline in EQ-5D Current Health VAS at Weeks 36 and 52

Top of page

End point title

Change From Baseline in EQ-5D Current Health VAS at Weeks 36 and 52 ^[207]

End point description

End point type

Secondary

End point timeframe

Baseline; Weeks 36, and 52

Notes
[207] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	472	477	319	189	189
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (BL)	48 ( 22.5 )	49 ( 22.8 )	47 ( 21.8 )	45 ( 21.6 )	47 ( 21.1 )
Change from BL at Week 36 (N=393,403,268,176,182)	21 ( 30.6 )	23 ( 28.5 )	20 ( 30.9 )	28 ( 28.2 )	24 ( 26.0 )
Change from BL at Week 52 (N=384,376,254,166,172)	25 ( 29.3 )	24 ( 28.5 )	24 ( 29.2 )	29 ( 28.6 )	23 ( 29.6 )

No statistical analyses for this end point

Secondary: Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA): Mean Percentage of Work Time Missed (Absenteeism) at Weeks 4, 12, and 24

Top of page

End point title

Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA): Mean Percentage of Work Time Missed (Absenteeism) at Weeks 4, 12, and 24

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Absenteeism (work time missed) due to RA: 100×{Q2/(Q2+Q4)}. Higher numbers indicate greater impairment and less productivity. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of work time missed
arithmetic mean (standard deviation)
Week 4 (N=191,185,112,161)	8.5 ( 21.27 )	6.6 ( 16.47 )	9.2 ( 21.99 )	9.4 ( 21.41 )
Week 12 (N=189,177,111,153)	6.6 ( 17.06 )	5.4 ( 14.56 )	7.1 ( 18.46 )	9.5 ( 22.66 )
Week 24 (N=178,168,112,132)	4.4 ( 13.54 )	3.6 ( 10.24 )	7.2 ( 17.72 )	10.5 ( 21.86 )

No statistical analyses for this end point

Secondary: WPAI-RA: Mean Percentage of Work Time Missed (Absenteeism) at Weeks 36 and 52

Top of page

End point title

WPAI-RA: Mean Percentage of Work Time Missed (Absenteeism) at Weeks 36 and 52 ^[208]

End point description

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[208] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of work time missed
arithmetic mean (standard deviation)
Week 36 (N=178,169,106,72,63)	5.5 ( 16.17 )	7.7 ( 19.46 )	7.0 ( 19.65 )	6.8 ( 19.79 )	8.4 ( 19.97 )
Week 52 (N=180,156,99,66,55)	4.8 ( 14.39 )	5.4 ( 15.10 )	7.4 ( 20.12 )	5.5 ( 13.24 )	5.8 ( 14.29 )

No statistical analyses for this end point

Secondary: WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 4, 12, and 24

Top of page

End point title

WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 4, 12, and 24

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Presenteeism (impairment while working) due to RA: 100×{Q5/10}. Higher numbers indicate greater impairment and less productivity. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of impairment while working
arithmetic mean (standard deviation)
Week 4 (N=185,182,108,156)	34.3 ( 22.69 )	36.9 ( 24.01 )	35.6 ( 22.39 )	42.5 ( 23.54 )
Week 12 (N=187,176,109,147)	26.3 ( 21.07 )	26.9 ( 22.57 )	27.6 ( 21.51 )	34.0 ( 21.98 )
Week 24 (N=177,168,110,128)	22.0 ( 21.28 )	21.0 ( 20.74 )	25.7 ( 21.99 )	30.9 ( 23.11 )

No statistical analyses for this end point

Secondary: WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 36 and 52

Top of page

End point title

WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 36 and 52 ^[209]

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Presenteeism (impairment while working) due to RA: 100×{Q5/10}. Higher numbers indicate greater impairment and less productivity. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[209] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of impairment while working
arithmetic mean (standard deviation)
Week 36 (N=176,166,103,71,62)	20.2 ( 19.54 )	19.6 ( 20.27 )	21.2 ( 20.74 )	21.5 ( 18.72 )	25.8 ( 23.51 )
Week 52 (N=179,155,97,66,55)	18.2 ( 18.83 )	17.3 ( 19.25 )	20.8 ( 21.78 )	22.3 ( 21.82 )	19.5 ( 20.04 )

No statistical analyses for this end point

Secondary: WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 4, 12, and 24

Top of page

End point title

WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 4, 12, and 24

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Work productivity loss (overall work impairment) due to RA: 100×{Q2/(Q2+Q4) + [(1-Q2/(Q2+Q4) × (Q5/10)]}. Higher numbers indicate greater impairment and less productivity. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of work productivity loss
arithmetic mean (standard deviation)
Week 4 (N=185,182,108,156)	37.0 ( 24.64 )	39.5 ( 25.17 )	38.4 ( 24.59 )	45.1 ( 25.18 )
Week 12 (N=187,176,109,147)	29.5 ( 24.25 )	29.3 ( 24.73 )	30.7 ( 24.34 )	36.7 ( 24.27 )
Week 24 (N=177,168,110,128)	24.4 ( 23.06 )	23.2 ( 22.64 )	29.1 ( 23.88 )	34.9 ( 26.04 )

No statistical analyses for this end point

Secondary: WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 36 and 52

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End point title

WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 36 and 52 ^[210]

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Work productivity loss (overall work impairment) due to RA: 100×{Q2/(Q2+Q4) + [(1-Q2/(Q2+Q4) × (Q5/10)]}. Higher numbers indicate greater impairment and less productivity. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[210] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of work productivity loss
arithmetic mean (standard deviation)
Week 36 (N=176,166,103,71,62)	23.3 ( 22.02 )	23.9 ( 23.98 )	23.8 ( 22.95 )	24.0 ( 21.33 )	29.1 ( 26.79 )
Week 52 (N=179,155,97,66,55)	20.6 ( 21.74 )	20.5 ( 22.15 )	24.3 ( 24.77 )	25.7 ( 24.32 )	22.3 ( 24.10 )

No statistical analyses for this end point

Secondary: WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 4, 12, and 24

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End point title

WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 4, 12, and 24

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Activity impairment due to RA: 100×{Q6/10}. If Question 1 (Are you currently employed?) is 'NO', then only the activity impairment score can be determined. Higher numbers indicate greater impairment and less productivity. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	475	480	325	475
Units: percentage of activity impairment
arithmetic mean (standard deviation)
Week 4 (N=468,471,319,457)	44.6 ( 24.18 )	46.2 ( 24.05 )	46.4 ( 23.84 )	52.1 ( 23.41 )
Week 12 (N=455,457,306,437)	35.1 ( 23.86 )	36.6 ( 24.51 )	38.3 ( 25.57 )	44.3 ( 23.73 )
Week 24 (N=416,419,277,372)	30.2 ( 24.69 )	30.4 ( 23.07 )	32.5 ( 24.40 )	39.3 ( 23.69 )

No statistical analyses for this end point

Secondary: WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 36 and 52

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End point title

WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 36 and 52 ^[211]

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Activity impairment due to RA: 100×{Q6/10}. If Question 1 (Are you currently employed?) is 'NO', then only the activity impairment score can be determined. Higher numbers indicate greater impairment and less productivity. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Weeks 36 and 52

Notes
[211] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	475	480	325	190	191
Units: percentage of activity impairment
arithmetic mean (standard deviation)
Week 36 (N=395,404,270,177,184)	28.3 ( 23.30 )	28.7 ( 23.47 )	31.3 ( 25.44 )	28.3 ( 22.47 )	32.3 ( 23.62 )
Week 52 (N=386,379,257,167,174)	26.0 ( 22.44 )	26.3 ( 22.71 )	28.1 ( 24.38 )	28.6 ( 23.57 )	28.9 ( 23.07 )

No statistical analyses for this end point

Secondary: Change From Baseline in WPAI-RA: Mean Percentage of Work Time Missed (Absenteeism) at Weeks 4, 12, and 24

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End point title

Change From Baseline in WPAI-RA: Mean Percentage of Work Time Missed (Absenteeism) at Weeks 4, 12, and 24

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Absenteeism (work time missed) due to RA: 100×{Q2/(Q2+Q4)}. Higher numbers indicate greater impairment and less productivity. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	195	193	127	162
Units: percentage of work time missed
arithmetic mean (standard deviation)
Baseline (BL)	12.0 ( 25.77 )	9.9 ( 20.91 )	16.0 ( 27.57 )	17.0 ( 29.52 )
Change from BL at Week 4 (N=176,169,107,143)	-1.4 ( 21.24 )	-2.1 ( 18.14 )	-7.5 ( 24.26 )	-5.7 ( 25.65 )
Change from BL at Week 12 (N=167,160,103,129)	-4.3 ( 22.55 )	-3.8 ( 18.37 )	-7.5 ( 28.79 )	-5.9 ( 27.94 )
Change from BL at Week 24 (N=157,148,100,110)	-6.1 ( 24.77 )	-3.8 ( 16.92 )	-9.3 ( 28.99 )	-1.5 ( 27.24 )

No statistical analyses for this end point

Secondary: Change From Baseline in WPAI-RA: Mean Percentage of Work Time Missed (Absenteeism) at Weeks 36 and 52

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End point title

Change From Baseline in WPAI-RA: Mean Percentage of Work Time Missed (Absenteeism) at Weeks 36 and 52 ^[212]

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Absenteeism (work time missed) due to RA: 100×{Q2/(Q2+Q4)}. Higher numbers indicate greater impairment and less productivity. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[212] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	195	193	127	76	62
Units: percentage of work time missed
arithmetic mean (standard deviation)
Baseline (BL)	12.0 ( 25.77 )	9.9 ( 20.91 )	16.0 ( 27.57 )	18.3 ( 31.61 )	14.6 ( 26.88 )
Change from BL at Week 36 (N=149,143,94,63,48)	-4.4 ( 24.04 )	-1.5 ( 24.41 )	-8.7 ( 27.43 )	-6.2 ( 30.25 )	-7.5 ( 25.00 )
Change from BL at Week 52 (N=154,131,89,55,43)	-6.8 ( 26.27 )	-1.7 ( 21.89 )	-7.1 ( 24.00 )	-7.4 ( 26.76 )	-8.9 ( 27.90 )

No statistical analyses for this end point

Secondary: Change From Baseline in WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 4, 12, and 24

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End point title

Change From Baseline in WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 4, 12, and 24

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Presenteeism (impairment while working) due to RA: 100×{Q5/10}. Higher numbers indicate greater impairment and less productivity. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	184	187	119	150
Units: percentage of impairment while working
arithmetic mean (standard deviation)
Baseline (BL)	49.1 ( 25.23 )	48.0 ( 24.61 )	50.8 ( 22.98 )	52.5 ( 25.89 )
Change from BL at Week 4 (N=166,164,100,132)	-15.1 ( 23.19 )	-10.2 ( 22.82 )	-15.3 ( 24.84 )	-9.5 ( 23.68 )
Change from BL at Week 12 (N=160,156,96,118)	-24.1 ( 25.83 )	-21.9 ( 23.22 )	-22.9 ( 24.88 )	-17.1 ( 27.24 )
Change from BL at Week 24 (N=151,146,93,102)	-27.4 ( 26.37 )	-25.9 ( 26.59 )	-23.3 ( 27.56 )	-21.2 ( 29.33 )

No statistical analyses for this end point

Secondary: Change From Baseline in WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 36 and 52

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End point title

Change From Baseline in WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 36 and 52 ^[213]

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Presenteeism (impairment while working) due to RA: 100×{Q5/10}. Higher numbers indicate greater impairment and less productivity. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[213] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	184	187	119	69	59
Units: percentage of impairment while working
arithmetic mean (standard deviation)
Baseline (BL)	49.1 ( 25.23 )	48.0 ( 24.61 )	50.8 ( 22.98 )	53.8 ( 26.35 )	53.6 ( 23.40 )
Change from BL at Week 36 (N=144,138,87,61,45)	-29.7 ( 26.73 )	-27.5 ( 26.28 )	-27.8 ( 29.90 )	-32.0 ( 26.82 )	-26.4 ( 29.86 )
Change from BL at Week 52 (N=144,128,84,52,40)	-31.7 ( 27.44 )	-29.5 ( 24.66 )	-29.4 ( 27.91 )	-30.6 ( 28.24 )	-32.5 ( 28.17 )

No statistical analyses for this end point

Secondary: Change From Baseline in WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 4, 12, and 24

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End point title

Change From Baseline in WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 4, 12, and 24

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Work productivity loss (overall work impairment) due to RA: 100×{Q2/(Q2+Q4) + [(1-Q2/(Q2+Q4) × (Q5/10)]}. Higher numbers indicate greater impairment and less productivity. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	184	187	119	150
Units: percentage of work productivity loss
arithmetic mean (standard deviation)
Baseline (BL)	51.3 ( 25.95 )	50.6 ( 25.87 )	54.3 ( 24.85 )	55.8 ( 27.33 )
Change from BL at Week 4 (N=166,164,100,132)	-14.6 ( 24.59 )	-10.2 ( 23.71 )	-16.8 ( 26.29 )	-10.0 ( 24.06 )
Change from BL at Week 12 (N=160,156,96,118)	-23.2 ( 28.18 )	-22.3 ( 24.34 )	-22.8 ( 26.61 )	-17.5 ( 28.09 )
Change from BL at Week 24 (N=151,146,93,102)	-27.1 ( 27.78 )	-26.3 ( 27.29 )	-23.6 ( 29.40 )	-19.3 ( 30.81 )

No statistical analyses for this end point

Secondary: Change From Baseline in WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 36 and 52

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End point title

Change From Baseline in WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 36 and 52 ^[214]

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Work productivity loss (overall work impairment) due to RA: 100×{Q2/(Q2+Q4) + [(1-Q2/(Q2+Q4) × (Q5/10)]}. Higher numbers indicate greater impairment and less productivity. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[214] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	184	187	119	69	59
Units: percentage of work productivity loss
arithmetic mean (standard deviation)
Baseline (BL)	51.3 ( 25.95 )	50.6 ( 25.87 )	54.3 ( 24.85 )	56.6 ( 27.36 )	57.1 ( 25.14 )
Change from BL at Week 36 (N=144,138,87,61,45)	-28.9 ( 27.16 )	-25.7 ( 29.54 )	-28.6 ( 31.48 )	-31.7 ( 30.53 )	-26.9 ( 31.02 )
Change from BL at Week 52 (N=144,128,84,52,40)	-31.6 ( 29.17 )	-28.4 ( 27.11 )	-29.3 ( 29.38 )	-30.3 ( 30.73 )	-32.7 ( 29.65 )

No statistical analyses for this end point

Secondary: Change From Baseline in WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 4, 12, and 24

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End point title

Change From Baseline in WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 4, 12, and 24

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Activity impairment due to RA: 100×{Q6/10}. If Question 1 (Are you currently employed?) is 'NO', then only the activity impairment score can be determined. Higher numbers indicate greater impairment and less productivity. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 4, 12, and 24

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo
Number of subjects analysed	472	477	319	469
Units: percentage of activity impairment
arithmetic mean (standard deviation)
Baseline (BL)	61.5 ( 22.74 )	60.5 ( 23.85 )	61.3 ( 21.20 )	62.2 ( 22.11 )
Change from BL at Week 4 (N=465,470,316,455)	-17.0 ( 22.46 )	-14.7 ( 22.07 )	-14.8 ( 23.36 )	-9.8 ( 20.98 )
Change from BL at Week 12 (N=452,455,303,432)	-26.5 ( 25.17 )	-24.1 ( 24.95 )	-22.6 ( 24.93 )	-16.9 ( 25.98 )
Change from BL at Week 24 (N=413,417,273,369)	-30.7 ( 26.20 )	-30.4 ( 25.45 )	-28.6 ( 24.99 )	-21.9 ( 27.78 )

No statistical analyses for this end point

Secondary: Change From Baseline in WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 36 and 52

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End point title

Change From Baseline in WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 36 and 52 ^[215]

End point description

The WPAI is a questionnaire that measures impairments in work activities in participants with RA which consists of 6 questions: Q1-currently employed; Q2-work time missed due to RA; Q3-work time missed due to other reasons; Q4-hours actually worked; Q5-degree RA affected productivity while working (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant from working); Q6-degree RA affected productivity in regular unpaid activities (0-10 VAS, with 0 indicating no effect and 10 indicating RA completely prevented the participant`s daily activities). Outcomes are expressed as impairment percentages: Activity impairment due to RA: 100×{Q6/10}. If Question 1 (Are you currently employed?) is 'NO', then only the activity impairment score can be determined. Higher numbers indicate greater impairment and less productivity. A negative change from baseline indicates improvement. Participants in the Full Analysis Set with available data were analyzed.

End point type

Secondary

End point timeframe

Baseline; Weeks 36 and 52

Notes
[215] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Not applicable for the arm 'Placebo never received Filgotinib' at the specified time points.

End point values	Filgotinib 200 mg	Filgotinib 100 mg	Adalimumab	Placebo to Filgotinib 200 mg	Placebo to Filgotinib 100 mg
Number of subjects analysed	472	477	319	189	189
Units: percentage of activity impairment
arithmetic mean (standard deviation)
Baseline (BL)	61.5 ( 22.74 )	60.5 ( 23.85 )	61.3 ( 21.20 )	62.9 ( 21.74 )	59.7 ( 22.10 )
Change from BL at Week 36 (N=393,402,268,176,182)	-32.6 ( 26.66 )	-31.5 ( 25.66 )	-30.2 ( 26.93 )	-34.9 ( 26.60 )	-27.5 ( 26.14 )
Change from BL at Week 52 (N=384,376,254,166,172)	-34.8 ( 26.74 )	-33.7 ( 26.44 )	-32.9 ( 26.03 )	-35.2 ( 28.00 )	-30.8 ( 25.99 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

First dose date up to last dose date (Maximum: 54 weeks) plus 30 days

Adverse event reporting additional description

The Safety Analysis Set included all participants who received at least 1 dose of study drug. Treatment relatedness refers to study drug filgotinib, adalimumab and placebo to match, not other background treatment (MTX).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Placebo to Filgotinib 100 mg

Reporting group description

Participants in the placebo arm were administered a PTM filgotinib 200 mg tablet orally, once daily+ a PTM filgotinib 100 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 24 weeks. Then the participants in the placebo arm were rerandomized to filgotinib 100 mg and were administered a filgotinib 100 mg tablet orally, once daily + PTM filgotinib 200 mg tablet orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 28.1 weeks.

Reporting group title

Placebo

Reporting group description

The Placebo arm included all participants who received placebo in the study. Participants were administered PTM filgotinib 200 mg tablets orally, once daily+ PTM filgotinib 100 mg tablets orally, once daily + PTM adalimumab 40 mg SC injection, once every 2 weeks in addition to a weekly stable dose of MTX, orally for median exposure of 24 weeks.

Reporting group title

Placebo to Filgotinib 200 mg

Reporting group description

Reporting group title

Adalimumab

Reporting group description

Reporting group title

Filgotinib 100 mg

Reporting group description

Reporting group title

Filgotinib 200 mg

Reporting group description

Serious adverse events	Placebo to Filgotinib 100 mg	Placebo	Placebo to Filgotinib 200 mg	Adalimumab	Filgotinib 100 mg	Filgotinib 200 mg
Total subjects affected by serious adverse events
subjects affected / exposed	8 / 191 (4.19%)	21 / 475 (4.42%)	7 / 190 (3.68%)	22 / 325 (6.77%)	40 / 480 (8.33%)	35 / 475 (7.37%)
number of deaths (all causes)	1	2	1	1	1	3
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Breast cancer stage I
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cervix carcinoma stage III
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leiomyosarcoma metastatic
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant glioma
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to liver
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	1 / 190 (0.53%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral artery occlusion
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	1 / 190 (0.53%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Metrorrhagia
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	1 / 191 (0.52%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine haemorrhage
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vaginal haemorrhage
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	2 / 475 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	1 / 190 (0.53%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
Alveolitis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Bronchiectasis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Organising pneumonia
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary fibrosis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Pulmonary oedema
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Rheumatoid lung
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Vocal cord polyp
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Adjustment disorder with depressed mood
subjects affected / exposed	1 / 191 (0.52%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lipase increased
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery restenosis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	1 / 190 (0.53%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Scapula fracture
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Angina unstable
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cor pulmonale chronic
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Coronary artery disease
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinus tachycardia
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	1 / 191 (0.52%)	0 / 475 (0.00%)	1 / 190 (0.53%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	2 / 480 (0.42%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Carotid artery stenosis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hemiplegia
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Pancytopenia
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Meniere's disease
subjects affected / exposed	1 / 191 (0.52%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vertigo
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Macular fibrosis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vitreous opacities
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
subjects affected / exposed	1 / 191 (0.52%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	2 / 480 (0.42%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer perforation
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal inflammation
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal haemorrhage
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mouth ulceration
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peptic ulcer
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	2 / 475 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Skin ulcer
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angioedema
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	1 / 190 (0.53%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dermatitis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	1 / 190 (0.53%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pustular psoriasis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prerenal failure
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal cell dysplasia
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
subjects affected / exposed	1 / 191 (0.52%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foot deformity
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc disorder
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	1 / 190 (0.53%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Limb asymmetry
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	1 / 190 (0.53%)	3 / 325 (0.92%)	4 / 480 (0.83%)	4 / 475 (0.84%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1	2 / 3	3 / 4	4 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2
Bronchitis
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	2 / 475 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Cellulitis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	1 / 480 (0.21%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis infective
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	2 / 475 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2
Urinary tract infection
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varicella
subjects affected / exposed	1 / 191 (0.52%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abscess limb
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 191 (0.52%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Candida infection
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Helicobacter infection
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infected skin ulcer
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infectious pleural effusion
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infective tenosynovitis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paronychia
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia fungal
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia pneumococcal
subjects affected / exposed	0 / 191 (0.00%)	1 / 475 (0.21%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	1 / 325 (0.31%)	0 / 480 (0.00%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Electrolyte imbalance
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypervitaminosis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	1 / 480 (0.21%)	0 / 475 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	0 / 191 (0.00%)	0 / 475 (0.00%)	0 / 190 (0.00%)	0 / 325 (0.00%)	0 / 480 (0.00%)	1 / 475 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo to Filgotinib 100 mg	Placebo	Placebo to Filgotinib 200 mg	Adalimumab	Filgotinib 100 mg	Filgotinib 200 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	23 / 191 (12.04%)	61 / 475 (12.84%)	36 / 190 (18.95%)	82 / 325 (25.23%)	142 / 480 (29.58%)	128 / 475 (26.95%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	3 / 191 (1.57%)	11 / 475 (2.32%)	7 / 190 (3.68%)	21 / 325 (6.46%)	25 / 480 (5.21%)	17 / 475 (3.58%)
occurrences all number	3	11	7	24	31	24
Aspartate aminotransferase increased
subjects affected / exposed	3 / 191 (1.57%)	9 / 475 (1.89%)	8 / 190 (4.21%)	17 / 325 (5.23%)	20 / 480 (4.17%)	12 / 475 (2.53%)
occurrences all number	3	9	9	19	29	16
Gastrointestinal disorders
Nausea
subjects affected / exposed	1 / 191 (0.52%)	7 / 475 (1.47%)	4 / 190 (2.11%)	6 / 325 (1.85%)	16 / 480 (3.33%)	26 / 475 (5.47%)
occurrences all number	1	7	4	6	19	30
Infections and infestations
Nasopharyngitis
subjects affected / exposed	6 / 191 (3.14%)	25 / 475 (5.26%)	7 / 190 (3.68%)	24 / 325 (7.38%)	48 / 480 (10.00%)	43 / 475 (9.05%)
occurrences all number	8	31	9	27	58	53
Upper respiratory tract infection
subjects affected / exposed	6 / 191 (3.14%)	14 / 475 (2.95%)	8 / 190 (4.21%)	21 / 325 (6.46%)	49 / 480 (10.21%)	41 / 475 (8.63%)
occurrences all number	6	16	10	27	65	49
Urinary tract infection
subjects affected / exposed	8 / 191 (4.19%)	6 / 475 (1.26%)	10 / 190 (5.26%)	17 / 325 (5.23%)	19 / 480 (3.96%)	18 / 475 (3.79%)
occurrences all number	8	6	10	20	21	21

More information

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Were there any global substantial amendments to the protocol? Yes

05 Jul 2016

• Terminology for the Open Label Extension study was changed to long-term extension (LTE) study • Updated study procedures to collect body weight at all study visits • Added urine biomarker samples as an exploratory endpoint • Updated study procedures to include Treatment Satisfaction Questionnaire for Medication (TSQM) collection at Day 1 and Week 12, 24, 36, and 52 visits. • Clarified eligibility criteria as needed • Updated Study Procedures, to reflect global protocol changes in study procedures and time points • Updated the Prior and Concomitant Medications section to clarify documentation of prior medications and restriction window on injectable corticosteroids • Updated to stipulate that viably frozen peripheral blood mononuclear cells and leukocyte subset samples would be drawn in the US and Canada only; removed peripheral blood mononuclear cell substudy • Clarified that the magnetic resonance imaging (MRI) substudy would be performed postrandomization within 7 days of first dose and at Week 12 within ± 7 days • Clarified that radiographs performed after randomization could be done ± 7 days of the scheduled visit • Added carotid artery ultrasound substudy at selected sites, when available • Updated Criteria for Interruption or Discontinuation of Study Treatment, to align across protocols

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants who Achieved an American College of Rheumatology (ACR) 20% Improvement (ACR20) Response at Week 12

Primary: Percentage of Participants who Achieved an American College of Rheumatology (ACR) 20% Improvement (ACR20) Response at Week 12

Secondary: Percentage of Participants who Achieved Disease Activity Score for 28 Joint Count Using C-Reactive Protein [DAS28 (CRP)] ≤ 3.2 at Week 12

Secondary: Percentage of Participants who Achieved Disease Activity Score for 28 Joint Count Using C-Reactive Protein [DAS28 (CRP)] ≤ 3.2 at Week 12

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

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

Secondary: Percentage of Participants who Achieved DAS28 (CRP) < 2.6 at Week 24

Secondary: Percentage of Participants who Achieved DAS28 (CRP) < 2.6 at Week 24

Secondary: Change from Baseline in Modified Total Sharp Score (mTSS) at Week 24

Secondary: Change from Baseline in Modified Total Sharp Score (mTSS) at Week 24

Secondary: Percentage of Participants who Achieved ACR 50% Improvement (ACR50) at Weeks 2, 4, 12, and 24

Secondary: Percentage of Participants who Achieved ACR 50% Improvement (ACR50) at Weeks 2, 4, 12, and 24

Secondary: Percentage of Participants Who Achieved ACR50 at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved ACR50 at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved ACR 70% Improvement (ACR70) at Weeks 2, 4, 12, and 24

Secondary: Percentage of Participants Who Achieved ACR 70% Improvement (ACR70) at Weeks 2, 4, 12, and 24

Secondary: Percentage of Participants Who Achieved ACR70 at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved ACR70 at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved ACR20 Response at Weeks 2, 4, and 24

Secondary: Percentage of Participants Who Achieved ACR20 Response at Weeks 2, 4, and 24

Secondary: Percentage of Participants Who Achieved ACR20 Response at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved ACR20 Response at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 2, 4, and 24

Secondary: Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 2, 4, and 24

Secondary: Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: Tender Joint Count Based on 68 Joints (TJC68) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: Tender Joint Count Based on 68 Joints (TJC68) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: TJC68 at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: TJC68 at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: Swollen Joint Count Based on 66 Joints (SJC66) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: Swollen Joint Count Based on 66 Joints (SJC66) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: SJC66 at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: SJC66 at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: Subject’s Global Assessment of Disease Activity (SGA) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: Subject’s Global Assessment of Disease Activity (SGA) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: SGA at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: SGA at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: Physician’s Global Assessment of Disease Activity (PGA) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: Physician’s Global Assessment of Disease Activity (PGA) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: PGA at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: PGA at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: Subject`s Pain Assessment at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: Subject`s Pain Assessment at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: Subject`s Pain Assessment at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: Subject`s Pain Assessment at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: High-Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: High-Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in Individual ACR Component: hsCRP at Weeks 36 and 52

Secondary: Change From Baseline in Individual ACR Component: hsCRP at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved an Improvement (Decrease) in the HAQ-DI Score ≥ 0.22 at Weeks 2, 4, 12, and 24

Secondary: Percentage of Participants Who Achieved an Improvement (Decrease) in the HAQ-DI Score ≥ 0.22 at Weeks 2, 4, 12, and 24

Secondary: Percentage of Participants Who Achieved an Improvement (Decrease) in the HAQ-DI Score ≥ 0.22 at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved an Improvement (Decrease) in the HAQ-DI Score ≥ 0.22 at Weeks 36 and 52

Secondary: Change From Baseline in DAS28 (CRP) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in DAS28 (CRP) at Weeks 2, 4, 12, and 24

Secondary: Change From Baseline in DAS28 (CRP) at Weeks 36 and 52

Secondary: Change From Baseline in DAS28 (CRP) at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 2, 4, and 24

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 2, 4, and 24

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) < 2.6 at Weeks 2, 4, and 12

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) < 2.6 at Weeks 2, 4, and 12

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) < 2.6 at Weeks 36 and 52

Secondary: Percentage of Participants Who Achieved DAS28 (CRP) < 2.6 at Weeks 36 and 52

Secondary: American College of Rheumatology N Percent Improvement (ACR-N) at Weeks 2, 4, 12, and 24

Secondary: American College of Rheumatology N Percent Improvement (ACR-N) at Weeks 2, 4, 12, and 24

Secondary: ACR N Percent Improvement (ACR-N) at Weeks 36 and 52

Secondary: ACR N Percent Improvement (ACR-N) at Weeks 36 and 52

Secondary: Number of Participants With European League Against Rheumatism (EULAR) Response at Weeks 2, 4, 12, and 24