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

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

    Results information
    Results version number
    		 v1
    This version publication date
    08 Oct 2023
    First version publication date
    08 Oct 2023
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    201791
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    GreatWest Road, Brentford,Middlesex, United Kingdom, TW8 9GS
    Public contact
    GlaxoSmithKline, GSK Response Center, +1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GlaxoSmithKline, GSK Response Center, +1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    09 Mar 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Jan 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy of GSK3196165 at doses of 90 mg and 150 mg weekly versus placebo for the treatment of participants with moderately to severely active RA who are on a stable background of csDMARDs and who have had an inadequate response to csDMARDs or bDMARDs.
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Jun 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 187
    Country: Number of subjects enrolled
    Colombia: 45
    Country: Number of subjects enrolled
    United Kingdom: 11
    Country: Number of subjects enrolled
    United States: 167
    Country: Number of subjects enrolled
    Bulgaria: 80
    Country: Number of subjects enrolled
    Estonia: 48
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Hungary: 28
    Country: Number of subjects enrolled
    Poland: 467
    Country: Number of subjects enrolled
    Spain: 11
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 27
    Country: Number of subjects enrolled
    Australia: 6
    Country: Number of subjects enrolled
    China: 165
    Country: Number of subjects enrolled
    Japan: 224
    Country: Number of subjects enrolled
    Mexico: 124
    Country: Number of subjects enrolled
    Russian Federation: 141
    Country: Number of subjects enrolled
    Thailand: 9
    Worldwide total number of subjects
    1764
    EEA total number of subjects
    658
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    1375
    From 65 to 84 years
    388
    85 years and over
    1

    Subject disposition

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

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

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

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

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

    Arm title
    		 GSK3196165 150mg + csDMARD (Global Cohort)
    Arm description
    		 Participants in Global Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

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

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

    Arm title
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)
    Arm description
    		 Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD from week 12 to week 52.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

    Arm title
    		 Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)
    Arm description
    		 Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD from week 12 to week 52.

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

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received Tofacitinib 5mg, capsule, orally, BID in combination with csDMARD plus placebo injection to maintain the blind from week 12 to week 52 weeks.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

    Arm title
    		 GSK3196165 90mg + csDMARD (Asia Cohort)
    Arm description
    		 Participants in Asia Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

    Arm title
    		 GSK3196165 150mg + csDMARD (Asia Cohort)
    Arm description
    		 Participants in Asia Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

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

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

    Arm title
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)
    Arm description
    		 Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD from week 12 to week 52.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

    Arm title
    		 Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)
    Arm description
    		 Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD from week 12 to week 52.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

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

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received Tofacitinib 5mg, capsule, orally, BID in combination with csDMARD plus placebo injection to maintain the blind from week 12 to week 52 weeks.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Placebo weekly SC injection in combination with csDMARD until Week 12.

    Number of subjects in period 1 [1]
    		GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort) GSK3196165 90mg + csDMARD (Asia Cohort) GSK3196165 150mg + csDMARD (Asia Cohort) Tofacitinib 5mg + csDMARD (Asia Cohort) Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort) Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort) Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
    Started
    545
    539
    271
    91
    89
    90
    47
    49
    19
    6
    8
    9
    Completed
    461
    447
    231
    73
    69
    68
    25
    23
    15
    4
    5
    4
    Not completed
    84
    92
    40
    18
    20
    22
    22
    26
    4
    2
    3
    5
         Physician decision
    5
    8
    4
    1
    5
    2
    4
    5
    -
    1
    -
    -
         Consent withdrawn by subject
    32
    35
    12
    8
    6
    8
    2
    3
    -
    -
    -
    1
         Adverse event, non-fatal
    23
    20
    16
    6
    4
    5
    1
    5
    -
    -
    1
    1
         STUDY TERMINATED BY SPONSOR
    -
    -
    -
    -
    -
    -
    8
    11
    2
    1
    2
    3
         PROTOCOL-SPECIFIED WITHDRAWAL CRITERION MET
    3
    12
    2
    -
    2
    1
    1
    1
    1
    -
    -
    -
         Lost to follow-up
    6
    5
    5
    1
    -
    2
    -
    -
    -
    -
    -
    -
         Lack of efficacy
    14
    12
    1
    2
    3
    4
    6
    1
    1
    -
    -
    -
         Protocol deviation
    1
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Total 1764 participants were randomized; one participant withdrew from 150mg GSK3196165 (Asia Cohort) before receiving intervention due to Physician Decision. The participant was removed from intent-to-treat and safety population (N=1763).

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    GSK3196165 90mg + csDMARD (Global Cohort)
    Reporting group description
    		 Participants in Global Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARD).

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

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

    Reporting group title
    Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)
    Reporting group description
    		 Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

    Reporting group title
    Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)
    Reporting group description
    		 Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

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

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

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

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

    Reporting group title
    Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)
    Reporting group description
    		 Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

    Reporting group title
    Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)
    Reporting group description
    		 Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

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

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

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    GSK3196165 90mg + csDMARD (Global Cohort)
    Reporting group description
    		 Participants in Global Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARD).

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

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

    Reporting group title
    Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort)
    Reporting group description
    		 Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

    Reporting group title
    Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)
    Reporting group description
    		 Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

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

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

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

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

    Reporting group title
    Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)
    Reporting group description
    		 Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

    Reporting group title
    Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)
    Reporting group description
    		 Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks

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

    Subject analysis set title
    Pooled Placebo (Global Cohort)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received Placebo weekly SC injection in combination with csDMARD until Week 12. The placebo arms are pooled into a single placebo arm.

    Subject analysis set title
    Pooled Placebo (Asia Cohort)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD until Week 12. The placebo arms are pooled into a single placebo arm.

    Subject analysis set title
    Tofacitinib 5mg + csDMARD (Global Cohort)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks

    Subject analysis set title
    Pooled Placebo (Global Cohort)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received Placebo weekly SC injection in combination with csDMARD until Week 12. The placebo arms are pooled into a single placebo arm.

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

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    End point title
    		 Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 superiority comparison with placebo (Global Cohort) [1]
    End point description
    ACR20 is calculated as 20% improvement from Baseline in Tender Joint Count 68 (TJC68), Swollen Joint Count 66 (SJC66) and 20% improvement in 3 of the following 5 measures:Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale [VAS] with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0=least difficulty to 3=extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as reference for the comparison of active treatment arms. The analysis was performed on Intent-to-Treat (ITT) set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Primary
    End point timeframe
    Week 12
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
        number (not applicable)
    54.9
    54.5
    71.1
    32.5
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The null hypothesis is defined as there is no difference between the 90mg dose of GSK3196165 and placebo in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 90mg dose of GSK3196165 differs from placebo in the proportion of participants achieving ACR20 response at Week 12.
    Comparison groups
    GSK3196165 90mg + csDMARD (Global Cohort) v Pooled Placebo (Global Cohort)
    Number of subjects included in analysis
    815
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.87
         upper limit
    		 3.53
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The null hypothesis is defined as there is no difference between the 150mg dose of GSK3196165 and placebo in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 150mg dose of GSK3196165 differs from placebo in the proportion of participants achieving ACR20 response at Week 12.
    Comparison groups
    GSK3196165 150mg + csDMARD (Global Cohort) v Pooled Placebo (Global Cohort)
    Number of subjects included in analysis
    809
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.85
         upper limit
    		 3.5
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    The null hypothesis is defined as there is no difference between the 05mg dose of Tofacitinib and placebo in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 05mg dose of Tofacitinib differs from placebo in the proportion of participants achieving ACR20 response at Week 12.
    Comparison groups
    Tofacitinib 5mg + csDMARD (Global Cohort) v Pooled Placebo (Global Cohort)
    Number of subjects included in analysis
    541
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.66
         upper limit
    		 7.9
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    The null hypothesis is defined as there is no difference between the 90 mg dose of GSK3196165 and 05mg dose of Tofacitinib in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 90 mg dose of GSK3196165 differs from 05mg dose of Tofacitinib in the proportion of participants achieving ACR20 response at Week 12.
    Comparison groups
    GSK3196165 90mg + csDMARD (Global Cohort) v Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects included in analysis
    816
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 0.66
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    The null hypothesis is defined as there is no difference between the 150mg dose of GSK3196165 and 05mg dose of Tofacitinib in the proportion of participants achieving ACR20 response at Week 12, versus the alternative hypothesis that the 150mg dose of GSK3196165 differs from 05mg dose of Tofacitinib in the proportion of participants achieving ACR20 response at Week 12.
    Comparison groups
    GSK3196165 150mg + csDMARD (Global Cohort) v Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 0.66

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

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    End point title
    		 Percentage (%) of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 (Asia Cohort) [2] [3]
    End point description
    ACR20 is calculated as 20% improvement from Baseline in Tender Joint Count 68 (TJC68), Swollen Joint Count 66 (SJC66) and 20% improvement in 3 of the following 5 measures:Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale [VAS] with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0=least difficulty to 3=extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)]. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as reference for the comparison of active treatment arms. The analysis was performed on ITT -Supplementary Asia Cohort set. Participants with data available at indicated timepoints are analyzed.
    End point type
    Primary
    End point timeframe
    Week 12
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary end point was descriptive analysis. Therefore, no statistical data are reported.
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Asia Cohort) GSK3196165 150mg + csDMARD (Asia Cohort) Tofacitinib 5mg + csDMARD (Asia Cohort) Pooled Placebo (Asia Cohort)
    Number of subjects analysed
    44
    42
    19
    21
    Units: Percentage of participants
        number (not applicable)
    45.0
    40.0
    68.0
    14.0
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving Clinical disease activity index (CDAI) total score less than or equal to (<=)10 [CDAI Low disease activity (LDA)] at Week 12 (Global Cohort) [4]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale [VAS] with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. For the purpose of all analyses up to week 12, the placebo arms were pooled into single placebo arm to primarily serve as reference for the comparison of active treatment arms. Analysis was performed on ITT set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
        number (not applicable)
    26.5
    25.1
    36.8
    11.4
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Global Cohort) [5]
    End point description
    Health Assessment Questionnaire-Disability Index (HAQ-DI) is 20-question instrument that assesses degree of difficulty in accomplishing tasks in eight functional areas:dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score is sum of domain scores divided by number of domains answered. The score ranges from 0 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline. For the purpose of all analyses up to week 12, placebo arms were pooled into single placebo arm to primarily serve as reference for comparison of active treatment arms. The analysis was performed on ITT set using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Scores on a scale
        least squares mean (standard error)
    -0.32 ( 0.029 )
    -0.31 ( 0.029 )
    -0.46 ( 0.037 )
    -0.14 ( 0.038 )
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving 20% improvement in ACR20 at Week 24: non-inferiority comparison with tofacitinib (Global Cohort) [6]
    End point description
    ACR20 is calculated as a 20% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) [visual analogue scale (VAS) with values from 0=best to 100=worst], Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein milligram per liter (mg/L) (hsCRP)]. The analysis was performed on the ITT set using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
        number (not applicable)
    65.0
    62.5
    79.8
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    GSK3196165 150mg + csDMARD (Global Cohort) v Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects included in analysis
    810
    Analysis specification
    Pre-specified
    Analysis type
    		 [7]
    Method
    		 Regression, Logistic
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -17.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.9
         upper limit
    		 -10.6
    Notes
    [7] - Non-inferiority over tofacitinib on ACR20 was concluded if the lower limit of the multiplicity corrected 95% Confidence Interval (CI) in the difference in proportions (GSK3196165 minus tofacitinib) was greater than -12%
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    GSK3196165 90mg + csDMARD (Global Cohort) v Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects included in analysis
    816
    Analysis specification
    Pre-specified
    Analysis type
    		 [8]
    Method
    		 Regression, Logistic
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -14.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.3
         upper limit
    		 -8.1
    Notes
    [8] - Non-inferiority over tofacitinib on ACR20 was concluded if the lower limit of the multiplicity corrected 95% Confidence Interval (CI) in the difference in proportions (GSK3196165 minus tofacitinib) was greater than -12%

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

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    End point title
    		 Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [9]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
    number (not applicable)
        Week 24
    32.8
    34.3
    49.6
        Week 52
    38.3
    38.0
    56.8
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving CDAI total score <=10 (CDAI LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort) [10]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Percentage of participants
    number (not applicable)
        Week 24
    37.5
    15.9
    46.4
        Week 52
    40.2
    38.2
    41.3
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 (Global Cohort) [11]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
        number (not applicable)
    4.7
    4.5
    9.7
    3.8
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [12]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
    number (not applicable)
        Week 24
    6.9
    7.2
    17.9
        Week 52
    11.9
    10.8
    21.2
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort) [13]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Percentage of participants
    number (not applicable)
        Week 24
    6.6
    5.7
    11.0
        Week 52
    11.4
    5.6
    17.2
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving 50%/70% improvement in American College of Rheumatology Criteria(ACR50/70) at Week 12 (Global Cohort) [14]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
    number (not applicable)
        ACR50
    21.6
    25.1
    39.4
    9.5
        ACR70
    6.9
    9.6
    18.9
    4.2
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving ACR50/70 at Week 24 and ACR20/50/70 Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [15]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
    number (not applicable)
        ACR20, Week 52
    64.3
    65.3
    75.6
        ACR50, Week 24
    31.6
    32.8
    53.6
        ACR50, Week 52
    36.5
    36.9
    52.9
        ACR70, Week 24
    14.0
    13.0
    28.7
        ACR70, Week 52
    19.1
    17.5
    35.7
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving ACR20/50/70 at Week 24 and Week 52 for placebo switched arms (Global Cohort) [16]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Percentage of participants
    number (not applicable)
        ACR20, Week 52
    56.3
    63.4
    70.1
        ACR50, Week 24
    35.6
    27.6
    41.8
        ACR50, Week 52
    43.7
    38.5
    47.2
        ACR70, Week 24
    18.7
    10.5
    21.8
        ACR70, Week 52
    22.6
    15.4
    20.7
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 (Global Cohort) [17]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score <=2.8. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
        number (not applicable)
    23.2
    23.6
    40.7
    10.4
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 (Global Cohort) [18]
    End point description
    The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
        number (not applicable)
    13.2
    14.6
    23.6
    7.3
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [19]
    End point description
    The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
    number (not applicable)
        Week 24
    31.3
    33.0
    55.3
        Week 52
    35.4
    36.4
    53.9
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [20]
    End point description
    The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
    number (not applicable)
        Week 24
    19.9
    24.1
    37.1
        Week 52
    26.2
    22.9
    38.8
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort) [21]
    End point description
    The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Percentage of participants
    number (not applicable)
        Week 24
    37.5
    19.3
    42.7
        Week 52
    41.4
    31.4
    39.6
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 and Week 52 for placebo switched arms (Global Cohort) [22]
    End point description
    The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Percentage of participants
    number (not applicable)
        Week 24
    30.2
    14.2
    23.4
        Week 52
    28.0
    16.6
    31.5
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 (Global Cohort) [23]
    End point description
    The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter [mm]/hour[hr]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
        number (not applicable)
    11.5
    12.0
    23.2
    5.5
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 (Global Cohort) [24]
    End point description
    The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
        number (not applicable)
    7.1
    6.1
    12.6
    3.8
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [25]
    End point description
    The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
    number (not applicable)
        Week 24
    16.7
    19.6
    38.0
        Week 52
    23.6
    21.2
    41.2
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [26]
    End point description
    The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
    number (not applicable)
        Week 24
    8.7
    11.7
    23.4
        Week 52
    14.3
    11.7
    19.9
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort) [27]
    End point description
    The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Percentage of participants
    number (not applicable)
        Week 24
    23.3
    11.5
    23.8
        Week 52
    30.4
    19.8
    26.4
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 24 and Week 52 for placebo switched arms (Global Cohort) [28]
    End point description
    The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Percentage of participants
    number (not applicable)
        Week 24
    13.4
    6.2
    13.4
        Week 52
    16.1
    11.5
    13.4
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving a good/moderate European league against rheumatism (EULAR) response at Week 12 (Global Cohort) [29]
    End point description
    DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response was defined based on combination of current DAS28 score and improvement in current score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response, >0.6 to <=1.2:moderate response, <=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:moderate response, <=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:no response, <=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. For purpose of all analyses up to week 12, placebo arms were pooled into single arm to primarily serve as reference for comparison of active treatment arms. Analysis was performed on ITT set using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
        number (not applicable)
    70.0
    71.3
    83.8
    46.3
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [30]
    End point description
    DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response was defined based on combination of current DAS28 score and improvement in current score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response, >0.6 to <=1.2:moderate response, <=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:moderate response, <=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:no response, <=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
    number (not applicable)
        Week 24
    79.8
    80.5
    90.4
        Week 52
    80.3
    78.9
    88.4
    No statistical analyses for this end point

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

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    End point title
    		 Number of participants achieving ACR/EULAR remission at Week 12 (Global Cohort) [31]
    End point description
    Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) <= 1, Swollen Joint Count 66 (SJC66) <= 1, high sensitivity C-reactive Protein (hsCRP) <= 1mg/dl and patient's global assessment of disease activity (PtGA) <= 10. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set that includes all randomized participants who received at least one dose of study treatment. This population was based on the treatment the participant was randomized to. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Participants
    13
    12
    15
    3
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving a good/moderate EULAR response at Week 24 and Week 52 for placebo switched arms (Global Cohort) [32]
    End point description
    DAS28-CRP and DAS28-ESR scores were categorized using EULAR response criteria. Response was defined based on combination of current DAS28 score and improvement in current score relative to Baseline. The definition of no response, moderate response and good response was as; DAS28 <=3.2 and DAS28 decrease from Baseline (>1.2:good response, >0.6 to <=1.2:moderate response, <=0.6:no response); DAS28 >3.2 to <=5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:moderate response, <=0.6:no response) and DAS28 >5.1 and DAS28 decrease from Baseline (>1.2:moderate response, >0.6 to <=1.2:no response, <=0.6:no response). If the post-Baseline DAS28-CRP score was missing, then the corresponding EULAR category was set to missing. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Percentage of participants
    number (not applicable)
        Week 24
    78.4
    73.0
    82.7
        Week 52
    74.5
    81.1
    81.5
    No statistical analyses for this end point

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

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    End point title
    		 Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for placebo switched arms (Global Cohort) [33]
    End point description
    Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) <= 1, Swollen Joint Count 66 (SJC66) <= 1, high sensitivity C-reactive Protein (hsCRP) <= 1mg/dl and patient's global assessment of disease activity (PtGA) <= 10. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    83
    75
    76
    Units: Participants
        Week 24, n=83,75,76
    4
    2
    3
        Week 52, n=74,68,67
    8
    4
    7
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving no radiographic progression Van der Heijde modified total sharp scores (mTSS) <= 0.5) at Week 12 (Global Cohort) [34]
    End point description
    Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Percentage of participants
        number (not applicable)
    88.2
    92.7
    94.1
    85.8
    No statistical analyses for this end point

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

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    End point title
    		 Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [35]
    End point description
    Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) <= 1, Swollen Joint Count 66 (SJC66) <= 1, high sensitivity C-reactive Protein (hsCRP) <= 1mg/dl and patient's global assessment of disease activity (PtGA) <= 10. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    497
    477
    247
    Units: Participants
        Week 24, n=497,477,247
    21
    18
    28
        Week 52, n=461,448,227
    37
    26
    27
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [36]
    End point description
    Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Percentage of participants
    number (not applicable)
        Week 24
    84.6
    89.9
    92.7
        Week 52
    78.2
    83.8
    87.7
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving no radiographic progression (mTSS <= 0.5) at Week 24 and Week 52 for placebo switched arms (Global Cohort) [37]
    End point description
    Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Percentage of participants
    number (not applicable)
        Week 24
    88.1
    82.2
    83.9
        Week 52
    85.6
    71.9
    87.9
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in CDAI total score at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [38]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale . CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -20.14 ( 0.669 )
    -20.68 ( 0.677 )
    -24.93 ( 0.848 )
        Week 52
    -20.84 ( 0.750 )
    -21.14 ( 0.762 )
    -24.87 ( 0.936 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in CDAI total score at Week 12 (Global Cohort) [39]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to 0-10 scale. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline. For the purpose of analyses up to week 12, the placebo arms were pooled into single placebo arm to primarily serve as reference for comparison of active treatment arms. Analysis was performed on ITT set. Multiple imputation method was used to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and week 12
    Notes
    [39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Scores on a scale
        least squares mean (standard error)
    -15.50 ( 0.680 )
    -16.31 ( 0.678 )
    -21.06 ( 0.878 )
    -9.56 ( 0.896 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in CDAI total score at Week 24 and Week 52 for placebo switched arms (Global Cohort) [40]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (VAS with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score <=10. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data. For efficacy assessments baseline is interpreted as Day 1.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -20.26 ( 1.334 )
    -16.78 ( 1.396 )
    -20.60 ( 1.385 )
        Week 52
    -20.52 ( 1.472 )
    -20.95 ( 1.547 )
    -22.01 ( 1.545 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12 (Global Cohort) [41]
    End point description
    DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score range from 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Scores on a scale
    least squares mean (standard error)
        DAS28-CRP
    -1.28 ( 0.064 )
    -1.35 ( 0.064 )
    -2.02 ( 0.082 )
    -0.71 ( 0.085 )
        DAS28-ESR
    -1.34 ( 0.066 )
    -1.40 ( 0.066 )
    -1.95 ( 0.084 )
    -0.73 ( 0.087 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for placebo switched arms (Global Cohort) [42]
    End point description
    DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score range from 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data. For efficacy assessments baseline is interpreted as Day 1.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Scores on a scale
    least squares mean (standard error)
        DAS28-CRP, Week 24
    -1.76 ( 0.139 )
    -1.39 ( 0.146 )
    -1.88 ( 0.145 )
        DAS28-CRP, Week 52
    -1.81 ( 0.156 )
    -1.70 ( 0.164 )
    -1.97 ( 0.165 )
        DAS28-ESR, Week 24
    -1.88 ( 0.144 )
    -1.48 ( 0.149 )
    -1.93 ( 0.148 )
        DAS28-ESR, Week 52
    -1.88 ( 0.165 )
    -1.74 ( 0.172 )
    -1.96 ( 0.169 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in DAS28-CRP/DAS28-ESR at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [43]
    End point description
    DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR) [ESR in millimeter/hour (mm/hr)] and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score range from 0-9.4, with higher scores indicating more disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Scores on a scale
    least squares mean (standard error)
        DAS28-CRP, Week 24
    -1.65 ( 0.070 )
    -1.71 ( 0.071 )
    -2.45 ( 0.089 )
        DAS28-CRP, Week 52
    -1.77 ( 0.079 )
    -1.76 ( 0.080 )
    -2.40 ( 0.098 )
        DAS28-ESR, Week 24
    -1.73 ( 0.073 )
    -1.79 ( 0.074 )
    -2.40 ( 0.092 )
        DAS28-ESR, Week 52
    -1.87 ( 0.084 )
    -1.82 ( 0.084 )
    -2.38 ( 0.102 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Van der Heijde mTSS at Week 12 (Global Cohort) [44]
    End point description
    Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Scores on a scale
        least squares mean (standard error)
    0.31 ( 0.072 )
    0.15 ( 0.073 )
    0.09 ( 0.092 )
    0.13 ( 0.095 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [45]
    End point description
    Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    0.42 ( 0.092 )
    0.32 ( 0.094 )
    0.15 ( 0.115 )
        Week 52
    0.84 ( 0.148 )
    0.46 ( 0.150 )
    0.30 ( 0.184 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in HAQ-DI at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [46]
    End point description
    HAQ-DI is a 20-question instrument that assesses the degree of difficulty of a participant in accomplishing tasks in eight functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of the domain scores divided by the number of domains answered. The total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -0.38 ( 0.033 )
    -0.37 ( 0.033 )
    -0.53 ( 0.041 )
        Week 52
    -0.40 ( 0.035 )
    -0.37 ( 0.035 )
    -0.52 ( 0.043 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Van der Heijde mTSS at Week 24 and Week 52 for placebo switched arms (Global Cohort) [47]
    End point description
    Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score range from 0 to 448 for mTSS with higher values representing higher disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data. For efficacy assessments baseline is interpreted as Day 1.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    0.18 ( 0.185 )
    0.51 ( 0.196 )
    0.21 ( 0.196 )
        Week 52
    -0.05 ( 0.288 )
    0.76 ( 0.304 )
    0.09 ( 0.307 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Arthritis pain VAS at Week 12 (Global Cohort) [48]
    End point description
    For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Scores on a scale
        least squares mean (standard error)
    -18.06 ( 1.266 )
    -17.13 ( 1.256 )
    -27.17 ( 1.610 )
    -10.28 ( 1.657 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in HAQ-DI at Week 24 and Week 52 for placebo switched arms (Global Cohort) [49]
    End point description
    HAQ-DI is a 20-question instrument that assesses degree of difficulty of participant in accomplishing tasks in 8 functional areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Overall HAQ-DI score was computed as sum of domain scores divided by number of domains answered. Total possible score ranges from 0 to 3 where 0=least difficulty and 3=extreme difficulty. Higher overall score indicates greater disability. Negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. Analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data. For efficacy assessments baseline is interpreted as Day 1.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 52
    Notes
    [49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -0.36 ( 0.065 )
    -0.38 ( 0.067 )
    -0.33 ( 0.067 )
        Week 52
    -0.30 ( 0.069 )
    -0.37 ( 0.070 )
    -0.40 ( 0.071 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for placebo switched arms (Global Cohort) [50]
    End point description
    For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who switched from placebo to study intervention at Week 12. Analysis was performed using multiple imputation method to handle missing data. For efficacy assessments baseline is interpreted as Day 1.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24 and Week 52
    Notes
    [50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -23.26 ( 2.710 )
    -18.45 ( 2.793 )
    -22.88 ( 2.791 )
        Week 52
    -23.71 ( 2.967 )
    -21.72 ( 3.071 )
    -21.62 ( 3.082 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [51]
    End point description
    For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24 and Week 52
    Notes
    [51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -23.32 ( 1.351 )
    -22.32 ( 1.371 )
    -31.27 ( 1.699 )
        Week 52
    -25.42 ( 1.506 )
    -25.14 ( 1.525 )
    -31.49 ( 1.846 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 domain scores at Week 12 (Global Cohort) [52]
    End point description
    SF-36 is a health-related survey that assesses quality of life covering 8 domains: physical functioning (PF), bodily pain (BP), role limitations due to physical/emotional problems, general health (GH), mental health (MH), social functioning (SF), vitality. The MCS consists of 4 domains (SF, MH, vitality, role-emotional) and PCS consists of 4 domains (PF, role-physical, BP, GH). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. Positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed for participants with data available at the indicated time points.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    506
    514
    252
    244
    Units: Scores on a scale
    least squares mean (standard error)
        Bodily Pain, n=506,514,252,244
    14.82 ( 20.264 )
    16.13 ( 20.997 )
    23.75 ( 22.916 )
    9.21 ( 21.040 )
        General Health, n=506,514,252,244
    7.48 ( 16.025 )
    6.74 ( 15.582 )
    10.48 ( 15.647 )
    5.16 ( 14.863 )
        Mental Health, n=506,514,252,244
    6.21 ( 17.655 )
    6.96 ( 18.312 )
    9.13 ( 19.229 )
    4.88 ( 18.257 )
        Physical Function, n=506,514,252,244
    12.78 ( 19.321 )
    14.47 ( 21.133 )
    18.63 ( 20.724 )
    8.42 ( 20.505 )
        Role Emotional, n=506,514,252,244
    6.41 ( 24.390 )
    7.90 ( 25.675 )
    9.85 ( 24.815 )
    7.00 ( 23.912 )
        Role Physical, n=506,514,252,244
    12.08 ( 21.650 )
    12.57 ( 22.044 )
    17.66 ( 21.724 )
    9.78 ( 20.593 )
        Social Function, n=506,514,252,244
    8.10 ( 23.132 )
    9.75 ( 25.484 )
    14.78 ( 25.900 )
    6.76 ( 23.984 )
        Vitality, n=506,514,252,244
    8.99 ( 18.971 )
    10.54 ( 19.349 )
    15.18 ( 21.491 )
    7.07 ( 18.624 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 mental component scores at Week 12 (Global Cohort) [53]
    End point description
    SF-36 survey evaluates health-related quality of life, covering physical functioning,bodily pain,role limitations due to physical/emotional issues,general health,mental health(MH),social functioning(SF),vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.MCS is primarily derived from 4 domains(SF,MH,vitality,role-emotional) representing overall mental health.Positive change from baseline, reported using T-score change, indicates improvement in overall mental health.Quality Metric software was used for scoring.Baseline was defined as most recent pre-dose NMV, including unscheduled visits.CB=subtracting PD value from BV.For analysis up to week 12, placebo arms were pooled into single arm to serve as reference for active treatment arm comparison.ITT set was analyzed using multiple imputation to manage missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: T-Score
        least squares mean (standard error)
    2.24 ( 0.474 )
    2.68 ( 0.471 )
    3.56 ( 0.604 )
    2.21 ( 0.624 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Short form (SF)-36 physical component scores at Week 12 (Global Cohort) [54]
    End point description
    SF-36 survey evaluates health-related quality of life, covering physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional issues,general health(GH),mental health,social functioning,vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health.Positive change from baseline, reported using T-score change, indicates improvement in overall physical health.Quality Metric software was used for scoring.Baseline was defined as most recent pre-dose NMV, including unscheduled visits.CB=subtracting PD value from BV.For analysis up to week 12, placebo arms were pooled into single arm to serve as reference for active treatment arm comparison.ITT set was analyzed using multiple imputation to manage missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: T-Score
        least squares mean (standard error)
    4.29 ( 0.363 )
    4.48 ( 0.361 )
    6.58 ( 0.464 )
    2.05 ( 0.478 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [55]
    End point description
    SF-36 survey evaluates health-related quality of life, covering physical functioning, bodily pain, role limitations due to physical/emotional issues, general health, mental health(MH), social functioning(SF), vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains(SF, MH, vitality, role-emotional) representing overall mental health. Positive change from baseline, reported using T-score change, indicates improvement in overall mental health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: T-Score
    least squares mean (standard error)
        Week 24
    2.69 ( 0.522 )
    3.16 ( 0.528 )
    4.80 ( 0.652 )
        Week 52
    3.06 ( 0.527 )
    3.38 ( 0.530 )
    4.08 ( 0.650 )
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [56]
    End point description
    SF-36 survey evaluates health-related quality of life, covering physical functioning(PF) ,bodily pain(BP) ,role limitations due to physical/emotional issues, general health(GH), mental health, social functioning, vitality. Each of 8 domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains(PF, role-physical, BP, GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: T-Score
    least squares mean (standard error)
        Week 24
    5.42 ( 0.416 )
    5.24 ( 0.421 )
    7.33 ( 0.520 )
        Week 52
    5.08 ( 0.460 )
    5.06 ( 0.464 )
    7.47 ( 0.569 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [57]
    End point description
    SF-36 is a health-related survey that assesses quality of life covering 8 domains: physical functioning (PF), bodily pain (BP), role limitations due to physical/emotional problems, general health (GH), mental health (MH), social functioning (SF), vitality. The MCS consists of 4 domains (SF, MH, vitality, role-emotional) and PCS consists of 4 domains (PF, role-physical, BP, GH). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. Positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed for participants with data available at the indicated time points.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    494
    486
    249
    Units: Scores on a scale
    least squares mean (standard error)
        Bodily Pain, Week 24, n=494,486,249
    18.06 ( 21.568 )
    18.87 ( 23.164 )
    26.26 ( 24.870 )
        Bodily Pain, Week 52, n=461,459,234
    19.38 ( 22.807 )
    20.50 ( 23.781 )
    27.01 ( 24.068 )
        General Health, Week 24, n=494,486,249
    8.80 ( 17.357 )
    8.18 ( 16.569 )
    11.82 ( 18.258 )
        General Health, Week 52, n=461,459,234
    8.72 ( 17.635 )
    8.74 ( 17.157 )
    12.71 ( 18.374 )
        Mental Health, Week 24, n=494,486,249
    7.33 ( 18.871 )
    7.81 ( 19.930 )
    11.24 ( 19.875 )
        Mental Health, Week 52, n=461,459,234
    8.03 ( 18.819 )
    8.21 ( 19.132 )
    9.87 ( 19.417 )
        Physical Function, Week 24, n=494,486,249
    16.20 ( 21.646 )
    16.59 ( 22.660 )
    21.73 ( 23.769 )
        Physical Function, Week 52, n=461,459,234
    16.90 ( 21.458 )
    17.40 ( 23.162 )
    22.31 ( 26.462 )
        Role Emotional, Week 24, n=494,486,249
    8.33 ( 27.318 )
    10.01 ( 24.860 )
    13.45 ( 24.656 )
        Role Emotional, Week 52, n=461,459,234
    9.31 ( 24.987 )
    10.77 ( 25.914 )
    13.85 ( 25.643 )
        Role Physical, Week 24, n=494,486,249
    15.51 ( 22.052 )
    15.60 ( 22.507 )
    18.90 ( 22.618 )
        Role Physical, Week 52, n=461,459,234
    15.58 ( 23.558 )
    16.29 ( 24.110 )
    21.98 ( 24.671 )
        Social Function, Week 24, n=494,486,249
    10.25 ( 24.377 )
    11.34 ( 26.893 )
    15.91 ( 27.581 )
        Social Function, Week 52, n=461,459,234
    11.23 ( 24.368 )
    12.06 ( 26.941 )
    14.42 ( 27.313 )
        Vitality, Week 24, n=494,486,249
    11.21 ( 20.320 )
    12.71 ( 20.389 )
    18.02 ( 22.463 )
        Vitality, Week 52, n=461,459,234
    12.96 ( 20.197 )
    12.58 ( 19.150 )
    16.35 ( 22.327 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 physical component scores at Week 24 and Week 52 for placebo switched arms (Global Cohort) [58]
    End point description
    SF-36 survey evaluates health-related quality of life, covering physical functioning(PF), bodily pain(BP), role limitations due to physical/emotional issues, general health(GH), MH, SF, vitality. Each domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains(PF, role-physical, BP, GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data. For efficacy assessments baseline is interpreted as Day 1.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: T-Score
    least squares mean (standard error)
        Week 24
    5.89 ( 0.821 )
    4.36 ( 0.851 )
    5.43 ( 0.857 )
        Week 52
    4.15 ( 0.902 )
    4.89 ( 0.929 )
    3.99 ( 0.941 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 mental component scores at Week 24 and Week 52 for placebo switched arms (Global Cohort) [59]
    End point description
    SF-36 survey evaluates health-related quality of life, covering PF, BP, role limitations due to physical/emotional issues, GH, mental health(MH), social functioning(SF), vitality. Each domains is scored using average, 0-100; higher score represents better health. MCS was aggregated across domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains(SF, MH, vitality, role-emotional) representing overall mental health. Positive change from baseline, reported using T-score change, indicates improvement in overall mental health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data. For efficacy assessments baseline is interpreted as Day 1.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: T-Score
    least squares mean (standard error)
        Week 24
    3.59 ( 1.041 )
    4.37 ( 1.076 )
    3.76 ( 1.082 )
        Week 52
    2.87 ( 1.051 )
    4.53 ( 1.081 )
    2.74 ( 1.092 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 domain scores at Week 24 and Week 52 for placebo switched arms (Global Cohort) [60]
    End point description
    SF-36 is a health-related survey that assesses quality of life covering 8 domains: physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health(MH),social functioning(SF),vitality. The MCS consists of 4 domains (SF,MH,vitality,role-emotional) and PCS consists of 4 domains (PF,role-physical,BP,GH). The individual question items are first summed, then domain scores are weighted to a scale between 0 to 100, where higher score represents better health. Positive change from baseline indicates an improvement. Quality Metric software was used for scoring for SF-36. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline value. For efficacy assessments baseline is interpreted as Day 1. ITT set was analyzed for participants with data available at the indicated time points.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    82
    76
    75
    Units: Scores on a scale
    least squares mean (standard error)
        Bodily Pain, Week 24, n=82,76,75
    19.61 ( 22.430 )
    17.93 ( 17.710 )
    22.73 ( 21.012 )
        Bodily Pain, Week 52, n=76,71,68
    18.43 ( 23.444 )
    19.35 ( 19.873 )
    20.69 ( 23.501 )
        General Health, Week 24, n=82,76,75
    9.34 ( 13.259 )
    8.96 ( 16.231 )
    8.35 ( 17.087 )
        General Health, Week 52, n=76,71,68
    6.16 ( 15.885 )
    10.52 ( 17.755 )
    6.69 ( 16.707 )
        Mental Health, Week 24, n=82,76,75
    8.72 ( 19.623 )
    10.20 ( 15.842 )
    8.87 ( 19.270 )
        Mental Health, Week 52, n=76,71,68
    8.68 ( 19.585 )
    12.25 ( 19.907 )
    8.60 ( 19.256 )
        Physical Function, Week 24, n=82,76,75
    16.89 ( 20.407 )
    17.30 ( 20.744 )
    16.93 ( 21.433 )
        Physical Function, Week 52, n=76,71,68
    13.55 ( 24.025 )
    19.72 ( 20.769 )
    18.53 ( 20.608 )
        Role Emotional, Week 24, n=82,76,75
    9.35 ( 26.495 )
    15.57 ( 25.325 )
    11.44 ( 27.901 )
        Role Emotional, Week 52, n=76,71,68
    6.91 ( 27.467 )
    16.78 ( 28.189 )
    10.29 ( 28.907 )
        Role Physical, Week 24, n=82,76,75
    16.92 ( 22.168 )
    17.02 ( 19.568 )
    20.17 ( 21.197 )
        Role Physical, Week 52, n=76,71,68
    14.80 ( 23.581 )
    20.86 ( 20.727 )
    17.46 ( 24.087 )
        Social Function, Week 24, n=82,76,75
    12.80 ( 25.381 )
    12.17 ( 25.247 )
    14.33 ( 24.634 )
        Social Function, Week 52, n=76,71,68
    8.55 ( 29.312 )
    16.20 ( 25.477 )
    15.26 ( 24.131 )
        Vitality, Week 24, n=82,76,75
    14.25 ( 18.770 )
    13.40 ( 18.839 )
    13.67 ( 21.100 )
        Vitality, Week 52, n=76,71,68
    13.32 ( 19.826 )
    12.50 ( 21.417 )
    11.31 ( 20.581 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12 (Global Cohort) [61]
    End point description
    The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the ITT set. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    270
    Units: Scores on a scale
        least squares mean (standard error)
    4.76 ( 0.482 )
    4.91 ( 0.479 )
    7.92 ( 0.615 )
    3.68 ( 0.637 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [62]
    End point description
    The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Participants who received study intervention from Day 1 to Week 52 were analyzed. Missing data was handled by multiple imputation method.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    545
    539
    271
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    6.10 ( 0.523 )
    6.12 ( 0.528 )
    8.37 ( 0.654 )
        Week 52
    6.97 ( 0.538 )
    6.41 ( 0.543 )
    8.38 ( 0.664 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for placebo switched arms (Global Cohort) [63]
    End point description
    The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Participants who received study intervention from Week 12 to Week 52 were analyzed. For efficacy assessments baseline is interpreted as Day 1. Missing data was handled by multiple imputation method.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    91
    89
    90
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    6.95 ( 1.034 )
    6.08 ( 1.072 )
    6.87 ( 1.070 )
        Week 52
    5.73 ( 1.061 )
    6.50 ( 1.096 )
    6.01 ( 1.105 )
    No statistical analyses for this end point

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

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    End point title
    		 Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) (Global Cohort) [64]
    End point description
    AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with use of a study intervention, whether or not considered related to study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs were included. Fifteen participants in Pooled placebo received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm. The analysis was performed on Safety Set that includes all randomized participants who received at least one dose of study treatment. Pooled Placebo collected data from Day 01 to Week 12. Placebo switched arms collected data from Week 12 to 59. Experimental arms collected data from Day 01 to Week 59.
    End point type
    Secondary
    End point timeframe
    Up to Week 59
    Notes
    [64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    545
    539
    286
    255
    Units: Participants
        AE
    420
    408
    127
    127
        SAE
    44
    43
    6
    6
        AESI
    72
    75
    5
    5
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in hematology parameter of white blood cell (WBC) count, platelet count, neutrophils, lymphocytes at Week 12 (Giga cells per liter) (Global Cohort) [65]
    End point description
    Blood samples were collected for the assessment of change from baseline in hematology parameters including WBC count, platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    494
    490
    267
    229
    Units: Giga cells per liter (10^9/L)
    arithmetic mean (standard deviation)
        Lymphocytes
    0.002 ( 0.5235 )
    -0.019 ( 0.5304 )
    0.045 ( 0.5477 )
    -0.011 ( 0.4783 )
        Neutrophils
    -0.444 ( 1.8305 )
    -0.647 ( 1.9192 )
    -1.054 ( 2.1874 )
    0.053 ( 1.9956 )
        Platelets
    -19.0 ( 50.74 )
    -19.9 ( 53.15 )
    -34.3 ( 64.33 )
    0.8 ( 54.75 )
        Leukocytes
    -0.45 ( 1.919 )
    -0.70 ( 1.992 )
    -1.02 ( 2.215 )
    0.02 ( 1.984 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in hematology parameter of WBC count, platelet count, neutrophils, lymphocytes at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [66]
    End point description
    Blood samples were collected for the assessment of change from baseline in hematology parameters including WBC count, platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    497
    480
    255
    Units: Giga cells per liter (10^9/L)
    arithmetic mean (standard deviation)
        Lymphocytes, Week 24
    0.004 ( 0.5092 )
    -0.017 ( 0.5188 )
    2.215 ( 0.5294 )
        Lymphocytes, Week 52
    0.001 ( 0.5679 )
    -0.012 ( 0.5487 )
    -0.143 ( 0.5739 )
        Neutrophils, Week 24
    -0.508 ( 1.7714 )
    -0.647 ( 2.0762 )
    -1.135 ( 2.2376 )
        Neutrophils, Week 52
    -0.594 ( 1.8490 )
    -0.788 ( 2.1627 )
    -1.022 ( 2.4346 )
        Platelets, Week 24
    -16.4 ( 61.73 )
    -21.0 ( 56.36 )
    -32.0 ( 63.74 )
        Platelets, Week 52
    -24.9 ( 66.31 )
    -22.0 ( 63.94 )
    -37.6 ( 70.56 )
        Leukocytes, Week 24
    -0.50 ( 1.818 )
    -0.66 ( 2.129 )
    -1.17 ( 2.269 )
        Leukocytes, Week 52
    -0.59 ( 1.976 )
    -0.80 ( 2.346 )
    -1.22 ( 2.465 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in hematology parameter of WBC count, platelet count, neutrophils, lymphocytes at Week 24 and Week 52 (Global Cohort) [67]
    End point description
    Blood samples were collected for the assessment of change from baseline in hematology parameters including WBC count, platelet count, neutrophils, lymphocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12), Week 24 and Week 52
    Notes
    [67] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    80
    74
    64
    Units: Giga cells per liter (10^9/L)
    arithmetic mean (standard deviation)
        Lymphocytes, Week 24
    -0.072 ( 0.4236 )
    0.014 ( 0.5442 )
    -0.042 ( 0.5563 )
        Lymphocytes, Week 52
    -0.085 ( 0.5077 )
    -0.071 ( 0.5098 )
    -0.243 ( 0.6030 )
        Neutrophils, Week 24
    -0.582 ( 1.6685 )
    -0.255 ( 2.1106 )
    -0.745 ( 1.9306 )
        Neutrophils, Week 52
    -0.605 ( 1.8343 )
    -0.288 ( 2.2031 )
    -0.617 ( 2.1111 )
        Platelets, Week 24
    -11.6 ( 58.77 )
    -13.6 ( 40.78 )
    -36.1 ( 62.88 )
        Platelets, Week 52
    -17.8 ( 39.56 )
    -21.1 ( 44.72 )
    -27.8 ( 72.75 )
        Leukocytes, Week 24
    -0.64 ( 1.669 )
    -0.25 ( 2.204 )
    -0.84 ( 2.093 )
        Leukocytes, Week 52
    -0.65 ( 2.148 )
    -0.38 ( 2.259 )
    -0.94 ( 2.134 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in hematology parameter of hemoglobin at Week 12 (Global Cohort) [68]
    End point description
    Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    492
    489
    267
    231
    Units: Grams per liter (g/L)
        arithmetic mean (standard deviation)
    0.8 ( 7.50 )
    0.1 ( 7.57 )
    0.4 ( 8.53 )
    -1.0 ( 7.57 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [69]
    End point description
    Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    497
    479
    255
    Units: Grams per liter (g/L)
    arithmetic mean (standard deviation)
        Week 24
    0.5 ( 8.89 )
    1.0 ( 8.57 )
    1.9 ( 9.23 )
        Week 52
    0.6 ( 10.83 )
    0.0 ( 10.12 )
    1.0 ( 10.35 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in hematology parameter of hemoglobin at Week 24 and Week 52 for placebo switched arms (Global Cohort) [70]
    End point description
    Blood samples were collected for the assessment of change from baseline in hematology parameters hemoglobin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12), Week 24 and Week 52
    Notes
    [70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    79
    74
    64
    Units: Grams per liter (g/L)
    arithmetic mean (standard deviation)
        Week 24
    1.2 ( 6.36 )
    1.2 ( 6.10 )
    3.2 ( 9.01 )
        Week 52
    0.8 ( 7.96 )
    1.8 ( 8.99 )
    2.1 ( 10.14 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in clinical chemistry parameter of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), Gamma-Glutamyl transpeptidase (GGT) at Week 12 (Global Cohort) [71]
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) and gamma-glutamyl transferase (GGT) levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    511
    504
    273
    231
    Units: International units per liter (IU/L)
    arithmetic mean (standard deviation)
        AP
    -1.3 ( 19.79 )
    0.4 ( 28.71 )
    -5.1 ( 19.95 )
    -1.6 ( 22.96 )
        ALT
    0.8 ( 14.14 )
    1.2 ( 13.49 )
    3.0 ( 15.73 )
    0.3 ( 15.88 )
        AST
    1.3 ( 8.34 )
    2.0 ( 11.35 )
    3.8 ( 12.23 )
    -0.1 ( 8.73 )
        GGT
    -1.5 ( 20.77 )
    0.3 ( 44.60 )
    -1.1 ( 17.60 )
    -1.7 ( 25.38 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [72]
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    497
    480
    257
    Units: International units per liter (IU/L)
    arithmetic mean (standard deviation)
        AP, Week 24
    -0.3 ( 23.40 )
    0.6 ( 20.47 )
    -7.9 ( 24.03 )
        AP, Week 52
    0.3 ( 20.20 )
    1.4 ( 22.40 )
    -5.1 ( 23.34 )
        ALT, Week 24
    1.0 ( 18.23 )
    4.6 ( 63.38 )
    4.1 ( 21.70 )
        ALT, Week 52
    -0.1 ( 14.16 )
    2.0 ( 16.35 )
    3.7 ( 15.33 )
        AST, Week 24
    1.2 ( 9.71 )
    3.8 ( 45.20 )
    4.2 ( 13.20 )
        AST, Week 52
    1.0 ( 8.08 )
    2.0 ( 11.47 )
    3.9 ( 11.17 )
        GGT, Week 24
    -1.2 ( 25.56 )
    0.5 ( 32.53 )
    -1.6 ( 16.76 )
        GGT, Week 52
    -1.0 ( 24.25 )
    0.2 ( 22.40 )
    -0.1 ( 17.49 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in clinical chemistry parameter of AST, ALT, AP, GGT at Week 24 and Week 52 for placebo switched arms (Global Cohort) [73]
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameters including AST, ALT, AP and GGT levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12), Week 24 and Week 52
    Notes
    [73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    83
    74
    64
    Units: International units per liter (IU/L)
    arithmetic mean (standard deviation)
        AP, Week 24
    -0.3 ( 15.77 )
    -3.5 ( 19.93 )
    -2.8 ( 23.41 )
        AP, Week 52
    -2.8 ( 19.07 )
    -1.6 ( 27.58 )
    -2.7 ( 26.76 )
        ALT, Week 24
    -0.2 ( 14.86 )
    0.2 ( 14.15 )
    6.4 ( 15.92 )
        ALT, Week 52
    1.0 ( 20.01 )
    0.7 ( 13.66 )
    7.8 ( 24.01 )
        AST, Week 24
    -0.2 ( 10.16 )
    1.4 ( 6.42 )
    5.0 ( 9.96 )
        AST, Week 52
    1.3 ( 14.54 )
    2.2 ( 7.07 )
    7.0 ( 16.92 )
        GGT, Week 24
    0.8 ( 20.15 )
    -2.0 ( 18.05 )
    0.0 ( 25.57 )
        GGT, Week 52
    -2.1 ( 15.84 )
    -1.1 ( 16.29 )
    0.8 ( 23.66 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in clinical chemistry parameter of total bilirubin at Week 12 (Global Cohort) [74]
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    506
    499
    271
    231
    Units: Micromoles per liter (umol/L)
        arithmetic mean (standard deviation)
    0.3 ( 2.84 )
    0.5 ( 2.68 )
    0.5 ( 3.11 )
    0.2 ( 2.78 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [75]
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    496
    477
    256
    Units: Micromoles per liter (umol/L)
    arithmetic mean (standard deviation)
        Week 24
    0.5 ( 2.66 )
    0.5 ( 2.78 )
    0.6 ( 2.73 )
        Week 52
    0.3 ( 2.66 )
    0.6 ( 2.80 )
    0.9 ( 2.83 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in clinical chemistry parameter of total bilirubin at Week 24 and Week 52 for placebo switched arms (Global Cohort) [76]
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameter total bilirubin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12), Week 24 and Week 52
    Notes
    [76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    81
    73
    64
    Units: Micromoles per liter (umol/L)
    arithmetic mean (standard deviation)
        Week 24
    0.3 ( 3.07 )
    0.3 ( 2.06 )
    0.4 ( 2.79 )
        Week 52
    -0.1 ( 2.88 )
    0.6 ( 2.44 )
    0.4 ( 2.20 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in clinical chemistry parameter of albumin at Week 12 (Global Cohort) [77]
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    511
    504
    273
    231
    Units: Grams per liter (g/L)
        arithmetic mean (standard deviation)
    0.1 ( 2.56 )
    0.1 ( 2.49 )
    1.1 ( 2.60 )
    -0.3 ( 2.72 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [78]
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    497
    479
    257
    Units: Grams per liter (g/L)
    arithmetic mean (standard deviation)
        Week 24
    0.2 ( 2.72 )
    0.3 ( 2.59 )
    1.6 ( 2.95 )
        Week 52
    0.3 ( 2.77 )
    0.3 ( 2.88 )
    1.3 ( 3.03 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in clinical chemistry parameter of albumin at Week 24 and Week 52 for placebo switched arms (Global Cohort) [79]
    End point description
    Blood samples were collected for the assessment of clinical chemistry parameter albumin level. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12), Week 24 and Week 52
    Notes
    [79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    83
    74
    64
    Units: Grams per liter (g/L)
    arithmetic mean (standard deviation)
        Week 24
    0.1 ( 2.33 )
    0.6 ( 2.13 )
    2.5 ( 2.99 )
        Week 52
    -0.0 ( 2.87 )
    0.9 ( 2.64 )
    2.1 ( 3.22 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of total cholesterol at Week 12 (Global Cohort) [80]
    End point description
    Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 4 and not Week 12 as no data collected. Week 4 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    0 [81]
    0 [82]
    0 [83]
    0 [84]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [81] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [82] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [83] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [84] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Global Cohort) [85]
    End point description
    Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    0 [86]
    0 [87]
    0 [88]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [86] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [87] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [88] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for placebo switched arms (Global Cohort) [89]
    End point description
    Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    0 [90]
    0 [91]
    0 [92]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [90] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [91] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [92] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [93]
    End point description
    Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 52
    Notes
    [93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    438
    437
    226
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    0.121 ( 0.8198 )
    0.129 ( 0.8076 )
    0.402 ( 0.8794 )
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for placebo switched arms (Global Cohort) [94]
    End point description
    Blood samples were collected for the assessment of lipid profile of total cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 52
    Notes
    [94] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    71
    66
    55
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    0.198 ( 0.9586 )
    0.255 ( 0.8086 )
    0.691 ( 0.9233 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for treatment arms who started study intervention from Day 1 (Global Cohort) [95]
    End point description
    Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    0 [96]
    0 [97]
    0 [98]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [96] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [97] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [98] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)-cholesterol at Week 12 (Global Cohort) [99]
    End point description
    Blood samples were collected for assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting post dose visit value from Baseline value. For purpose of all analyses up to week 12, placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for lipid panel is Week 4 and not Week 12 as no data collected. Week 4 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [99] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    0 [100]
    0 [101]
    0 [102]
    0 [103]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [100] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [101] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [102] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [103] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 24 for placebo switched arms (Global Cohort) [104]
    End point description
    Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    0 [105]
    0 [106]
    0 [107]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [105] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [106] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [107] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [108]
    End point description
    Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 52
    Notes
    [108] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    438
    437
    226
    Units: Millimoles per liter (mmol/L)
    arithmetic mean (standard deviation)
        HDL Cholesterol, Direct, n=438,437,226
    0.026 ( 0.2415 )
    0.010 ( 0.2812 )
    0.157 ( 0.3184 )
        LDL Cholesterol, n=432,436,226
    0.076 ( 0.6971 )
    0.093 ( 0.6396 )
    0.191 ( 0.7423 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for placebo switched arms who started study intervention from Week 12 (Global Cohort)

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    End point title
    		 Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for placebo switched arms who started study intervention from Week 12 (Global Cohort) [109]
    End point description
    Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 52
    Notes
    [109] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    71
    66
    55
    Units: Millimoles per liter (mmol/L)
    arithmetic mean (standard deviation)
        HDL Cholesterol, Direct, n=71,66,55
    -0.041 ( 0.2841 )
    0.045 ( 0.2769 )
    0.135 ( 0.3094 )
        LDL Cholesterol, n=71,65,55
    0.188 ( 0.7796 )
    0.184 ( 0.6039 )
    0.495 ( 0.7375 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of triglycerides at Week 24 for treatment arms who started study intervention from Day 1 (Global Cohort) [110]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    0 [111]
    0 [112]
    0 [113]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [111] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [112] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [113] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of triglycerides at Week 12 (Global Cohort) [114]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Blood samples were collected at indicated time points as per schedule of assessment in the protocol. The Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 12 was a secondary objective, however for the lipid panel, there is no corresponding time point in the schedule of assessment. Consequently, the only objective that can be assessed for the lipid panel is Week 4 and not at Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [114] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort) Pooled Placebo (Global Cohort)
    Number of subjects analysed
    0 [115]
    0 [116]
    0 [117]
    0 [118]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [115] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [116] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [117] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [118] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Change from Baseline in lipid profile parameter of triglycerides at Week 24 for placebo switched arms (Global Cohort) [119]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. Blood samples were collected at indicated time points per schedule of assessment in protocol. Objectives and Endpoints section incorrectly states that Change from baseline in key laboratory parameters at Week 24 was a secondary objective, however for lipid panel, there is no corresponding time point in schedule of assessment. Consequently, the objective that can be assessed for the lipid panel is Week 16 and not Week 24 as no data collected. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [119] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo+csDMARD and GSK3196165 90mg+csDMARD (Global Cohort) Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort) Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
    Number of subjects analysed
    0 [120]
    0 [121]
    0 [122]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [120] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [121] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [122] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Change from Baseline in lipid profile parameter of triglycerides at Week 52 for treatment arms who started study intervention from Day 1 (Global Cohort) [123]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on the Safety Set. Fifteen participants in Placebo group received active treatment of Tofacitinib mistakenly from Week 4 instead of Week 12 as planned. They were added with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 52
    Notes
    [123] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD (Global Cohort) GSK3196165 150mg + csDMARD (Global Cohort) Tofacitinib 5mg + csDMARD (Global Cohort)
    Number of subjects analysed
    438
    437
    226
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    0.045 ( 0.5902 )
    0.054 ( 0.5970 )
    0.117 ( 0.6444 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 52 for placebo switched arms who started study intervention from Week 12 (Global Cohort)

    		 Close Top of page
    End point title
    		 Change from Baseline in lipid profile parameter of triglycerides at Week 52 for placebo switched arms who started study intervention from Week 12 (Global Cohort) [124]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. The analysis was performed on