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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 methotrexate in participants with moderately to severely active rheumatoid arthritis who have an inadequate response to methotrexate

    Summary
    EudraCT number
    		 2019-000797-39
    Trial protocol
    		 GB   LV   ES   PL   LT   CZ   HU   IT  
    Global end of trial date
    16 Aug 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    15 Oct 2023
    First version publication date
    27 Aug 2023
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    201790
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03980483
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 GreatWest Road, Brentford, Middlesex, United Kingdom, TW8 9GS
    Public contact
    GSK Response Center, GlaxoSmithKline, +1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, +1 8664357343, GSKClinicalSupportHD@gsk.com
    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
    04 Oct 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Aug 2022
    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 MTX and who have had an inadequate response to MTX.
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 May 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: 163
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    China: 13
    Country: Number of subjects enrolled
    Czechia: 48
    Country: Number of subjects enrolled
    Hungary: 35
    Country: Number of subjects enrolled
    India: 103
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Latvia: 11
    Country: Number of subjects enrolled
    Lithuania: 40
    Country: Number of subjects enrolled
    Malaysia: 6
    Country: Number of subjects enrolled
    Mexico: 49
    Country: Number of subjects enrolled
    Poland: 451
    Country: Number of subjects enrolled
    Russian Federation: 100
    Country: Number of subjects enrolled
    Serbia: 20
    Country: Number of subjects enrolled
    South Africa: 116
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Ukraine: 247
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    United States: 123
    Worldwide total number of subjects
    1537
    EEA total number of subjects
    591
    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)
    1267
    From 65 to 84 years
    269
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were randomized in a ratio of 6:6:3:1:1:1 to 3 experimental and 3 Placebo arms. At Week 12, participants randomized to one of the three placebo arms switched to experimental arms, receiving the active intervention for 40 weeks. Participants randomized to experimental arms from study day 1, received the active intervention for 52 weeks.

    Pre-assignment
    Screening details
    		 Analysis of this study were reported for GSK3196165 90mg, GSK3196165 150mg, Tofacitinib 5 mg and all placebo arms are pooled to a single group to serve as reference for comparison of active treatment arms versus Placebo for primary efficacy endpoint analysis at Week 12.

    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 + MTX
    Arm description
    		 Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with methotrexate (MTX).
    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 90mg of GSK3196165 once every week.

    Arm title
    		 GSK3196165 150mg + MTX
    Arm description
    		 Participants received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with MTX.
    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 150mg of GSK3196165 once every week.

    Arm title
    		 Tofacitinib 5mg + MTX
    Arm description
    		 Participants received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with MTX 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 5mg of Tofacitinib once every alternate week.

    Arm title
    		 Placebo + MTX and GSK3196165 90mg + MTX
    Arm description
    		 Participants received Placebo weekly SC injection in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with MTX until Week 52.
    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 90mg of GSK3196165 once every week 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 once every week until Week 12

    Arm title
    		 Placebo + MTX and GSK3196165 150mg + MTX
    Arm description
    		 Participants received Placebo weekly SC injection in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with MTX until Week 52.
    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 150mg of GSK3196165 once every week 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 once every week until Week 12.

    Arm title
    		 Placebo + MTX and Tofacitinib 5mg + MTX
    Arm description
    		 Participants received Placebo tablet weekly in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo tablet to Tofacitinib 5mg, capsule, orally, BID in combination with MTX 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 5mg of Tofacitinib once every alternate week 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 once every week until Week 12.

    Number of subjects in period 1
    		GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Started
    513
    510
    258
    85
    86
    85
    Completed
    431
    436
    221
    69
    73
    75
    Not completed
    82
    74
    37
    16
    13
    10
         Physician decision
    14
    10
    7
    4
    4
    2
         Consent withdrawn by subject
    38
    21
    15
    5
    3
    4
         Adverse event, non-fatal
    13
    29
    11
    2
    2
    2
         UNKNOWN
    -
    1
    -
    -
    -
    -
         PROTOCOL-SPECIFIED WITHDRAWAL CRITERION MET
    4
    -
    1
    -
    1
    1
         INVESTIGATOR SITE CLOSED
    -
    1
    -
    -
    -
    -
         Lost to follow-up
    2
    4
    2
    1
    2
    -
         Lack of efficacy
    7
    6
    -
    3
    1
    1
         Protocol deviation
    4
    2
    1
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GSK3196165 90mg + MTX
    Reporting group description
    		 Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with methotrexate (MTX).

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

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

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

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

    Reporting group title
    Placebo + MTX and Tofacitinib 5mg + MTX
    Reporting group description
    		 Participants received Placebo tablet weekly in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo tablet to Tofacitinib 5mg, capsule, orally, BID in combination with MTX plus placebo injection to maintain the blind for 52 weeks.

    Reporting group values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX Total
    Number of subjects
    		 513 510 258 85 86 85 1537
    Age categorical
    Units: Subjects
        <=18 years
    		 0 0 0 0 0 0 0
        Between 18 and 65 years
    		 417 426 205 72 71 76 1267
        >=65 years
    		 96 84 53 13 15 9 270
    Age Continuous
    Units: YEARS
        arithmetic mean (standard deviation)
    		 53.7 ( 12.14 ) 54.2 ( 10.77 ) 54.3 ( 11.66 ) 51.3 ( 13.12 ) 52.7 ( 12.41 ) 53.2 ( 10.24 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 401 399 209 62 72 68 1211
        Male
    		 112 111 49 23 14 17 326
    Race/Ethnicity, Customized
    Units: Subjects
        AMERICAN INDIAN OR ALASKA NATIVE
    		 11 11 9 2 3 2 38
        ASIAN
    		 48 39 29 5 7 4 132
        BLACK OR AFRICAN AMERICAN
    		 11 11 12 3 2 2 41
        MISSING
    		 1 0 0 1 1 1 4
        MULTIPLE
    		 10 15 7 2 2 1 37
        WHITE
    		 432 434 201 72 71 75 1285
    Subject analysis sets

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

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

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

    Subject analysis sets values
    		 Pooled Placebo Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects
    256
    273
    241
    Age categorical
    Units: Subjects
        <=18 years
        Between 18 and 65 years
        >=65 years
    Age Continuous
    Units: YEARS
        arithmetic mean (standard deviation)
    42.7 ( )
    ( )
    ( )
    Sex: Female, Male
    Units: Participants
        Female
        Male
    Race/Ethnicity, Customized
    Units: Subjects
        AMERICAN INDIAN OR ALASKA NATIVE
        ASIAN
        BLACK OR AFRICAN AMERICAN
        MISSING
        MULTIPLE
        WHITE

    End points

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    End points reporting groups
    Reporting group title
    GSK3196165 90mg + MTX
    Reporting group description
    		 Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with methotrexate (MTX).

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

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

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

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

    Reporting group title
    Placebo + MTX and Tofacitinib 5mg + MTX
    Reporting group description
    		 Participants received Placebo tablet weekly in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo tablet to Tofacitinib 5mg, capsule, orally, BID in combination with MTX plus placebo injection to maintain the blind for 52 weeks.

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

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

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

    Primary: Percentage of participants achieving 20 percentage (%) improvement in American College of Rheumatology Criteria (ACR20) at Week 12 superiority comparison with placebo

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    End point title
    		 Percentage of participants achieving 20 percentage (%) improvement in American College of Rheumatology Criteria (ACR20) at Week 12 superiority comparison with placebo [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
        number (not applicable)
    54.7
    50.9
    63.6
    42.7
    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 + MTX v Pooled Placebo
    Number of subjects included in analysis
    769
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0023
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.62
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 1.19
         upper limit
    		 2.21
    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 + MTX v Pooled Placebo
    Number of subjects included in analysis
    766
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0362
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.39
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 1.89
    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 + MTX v Tofacitinib 5mg + MTX
    Number of subjects included in analysis
    768
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0013
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.59
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 0.82
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    The null hypothesis is defined as there is no difference between the 90mg 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 90mg dose of GSK3196165 differs from 05mg dose of Tofacitinib in the proportion of participants achieving ACR20 response at Week 12.
    Comparison groups
    GSK3196165 90mg + MTX v Tofacitinib 5mg + MTX
    Number of subjects included in analysis
    771
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.023
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.69
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 0.95
    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 + MTX v Pooled Placebo
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.34
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 1.62
         upper limit
    		 3.37

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

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    End point title
    		 Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 [2]
    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
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Scores on a scale
        least squares mean (standard error)
    -0.46 ( 0.025 )
    -0.38 ( 0.024 )
    -0.5 ( 0.034 )
    -0.27 ( 0.034 )
    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

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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 [3]
    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. 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
        number (not applicable)
    20.9
    19.8
    32.5
    13.9
    No statistical analyses for this end point

    Secondary: Percentage of participants achieving 20% improvement in ACR20 at Week 24 (Non-Inferiority versus tofacitinib)

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    End point title
    		 Percentage of participants achieving 20% improvement in ACR20 at Week 24 (Non-Inferiority versus tofacitinib) [4]
    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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
        number (not applicable)
    63.9
    61.3
    74.4
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    GSK3196165 150mg + MTX v Tofacitinib 5mg + MTX
    Number of subjects included in analysis
    768
    Analysis specification
    Pre-specified
    Analysis type
    		 [5]
    Method
    		 Regression, Logistic
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -13
    Confidence interval
         level
    		 0.98%
         sides
    2-sided
         lower limit
    		 -21.2
         upper limit
    		 -4.8
    Notes
    [5] - Non-inferiority over tofacitinib on ACR20 was concluded if the lower limit of the multiplicity corrected 97.5% CI in the difference in proportions (GSK3196165 minus tofacitinib) was greater than -12%
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    GSK3196165 90mg + MTX v Tofacitinib 5mg + MTX
    Number of subjects included in analysis
    771
    Analysis specification
    Pre-specified
    Analysis type
    		 [6]
    Method
    		 Regression, Logistic
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -10.4
    Confidence interval
         level
    		 0.98%
         sides
    2-sided
         lower limit
    		 -18.6
         upper limit
    		 -2.3
    Notes
    [6] - Non-inferiority over tofacitinib on ACR20 was concluded if the lower limit of the multiplicity corrected 97.5 % Confidence Interval (CI) in the difference in proportions (GSK3196165 minus tofacitinib) was greater than -12%

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

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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 [7]
    End point description
    ACR50/70 is calculated as 50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and 50%/70% improvement in 3 of the following 5 measures:Patient's Global Assessment of Arthritis Disease Activity (PtGA), Physician Global Assessment of Arthritis Disease Activity (PhGA) [VAS with values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (ranges from 0 = least difficulty to 3 = extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP)]. For the purpose of all analyses up to week 12, placebo arms were pooled into single placebo arm to primarily serve as reference for comparison of active treatment arms. The analysis was performed on the ITT set using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
    number (not applicable)
        ACR50, Week 12
    23.3
    20.0
    34.1
    12.2
        ACR70, Week 12
    8.5
    6.1
    13.9
    3.5
    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 24 and ACR 20/50/70 at and Week 52 for treatment arms who started study intervention from Day 1

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    End point title
    		 Percentage of participants achieving 50%/70% improvement in American College of Rheumatology Criteria (ACR50/70) at Week 24 and ACR 20/50/70 at and Week 52 for treatment arms who started study intervention from Day 1 [8]
    End point description
    ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) [VAS with values from 0=best to 100=worst], Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ- DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein mg/L (hsCRP)]. 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
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
    number (not applicable)
        ACR20, Week 52
    63.9
    61.1
    75.8
        ACR50, Week 24
    31.4
    29.1
    46.7
        ACR50, Week 52
    35.0
    34.2
    48.4
        ACR70, Week 24
    12.5
    10.1
    25.1
        ACR70, Week 52
    16.7
    14.4
    26.9
    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

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    End point title
    		 Percentage of participants achieving ACR20/50/70 at Week 24 and Week 52 for placebo switched arms [9]
    End point description
    ACR20/50/70 is calculated as a 20%/50%/70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 20%/50%/70% improvement in 3 of the following 5 measures: Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale (VAS) with values from 0=best to 100=worst), Physician Global Assessment of Arthritis Disease Activity (PhGA) [VAS with values from 0=best to 100=worst], Patient Assessment of Arthritis Pain (VAS with values from 0=no pain and 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ- DI) (ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty) and an acute-phase reactant [high sensitivity C-reactive Protein mg/L (hsCRP)]. 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Percentage of participants
    number (not applicable)
        ACR20, Week 24
    56.7
    71.2
    69.9
        ACR20, Week 52
    70.5
    67.8
    84.6
        ACR50, Week 24
    37.0
    35.0
    40.7
        ACR50, Week 52
    28.6
    42.5
    50.7
        ACR70, Week 24
    7.9
    15.0
    19.6
        ACR70, Week 52
    10.3
    20.2
    25.8
    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 treatment arms who started study intervention from Day 1

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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 [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 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
    number (not applicable)
        Week 24
    29.9
    29.8
    45.9
        Week 52
    35.5
    37.1
    51.7
    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

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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 [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. 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Percentage of participants
    number (not applicable)
        Week 24
    32.9
    37.4
    45.8
        Week 52
    38.5
    44
    52.4
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving CDAI total score <=2.8 (CDAI Remission) at Week 12 [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. 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
        number (not applicable)
    3.8
    2.4
    5.8
    1.0
    No statistical analyses for this end point

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

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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 [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 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
    number (not applicable)
        Week 24
    6.1
    5.2
    12.1
        Week 52
    9.4
    4.4
    15.1
    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

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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 [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 24 and Week 52
    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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Percentage of participants
    number (not applicable)
        Week 24
    4.4
    8.4
    6.4
        Week 52
    4.6
    9.6
    11.1
    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

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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 [15]
    End point description
    The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
        number (not applicable)
    20.2
    19.4
    33.5
    11.3
    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

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    End point title
    		 Percentage of participants achieving DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 [16]
    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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
        number (not applicable)
    13.6
    12.2
    19.7
    8.2
    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

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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 [17]
    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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
    number (not applicable)
        Week 24
    17.2
    18.3
    28.3
        Week 52
    23.3
    18.7
    34.1
    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

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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 [18]
    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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
    number (not applicable)
        Week 24
    26.8
    29.0
    47.4
        Week 52
    32.8
    31.3
    49.8
    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

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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 [19]
    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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Percentage of participants
    number (not applicable)
        Week 24
    20.7
    22.7
    30.4
        Week 52
    22.9
    21.8
    30.3
    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 placebo switched arms

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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 [20]
    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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Percentage of participants
    number (not applicable)
        Week 24
    26.3
    31.0
    44.9
        Week 52
    34.2
    34.9
    50.2
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 [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. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. For the purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as a reference for the comparison of active treatment arms. Analysis was performed using multiple imputation method to handle missing data. 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
        number (not applicable)
    10.3
    8.4
    17.1
    5.2
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants achieving DAS28 ESR <2.6 (DAS28-ESR Remission) at Week 12 [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 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
        number (not applicable)
    6.0
    5.3
    11.5
    5.2
    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

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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 [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 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
    number (not applicable)
        Week 24
    8.6
    7.8
    13.7
        Week 52
    14.1
    8.8
    18.7
    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

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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 [24]
    End point description
    The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-CRP less than (<)2.6. A negative change from baseline in DAS28-CRP indicates an improvement. The analysis was performed on all randomized participants who received study intervention from Day 01 to Week 52. Analysis was performed using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
    number (not applicable)
        Week 24
    14.5
    14.1
    26.3
        Week 52
    19.3
    15.3
    34.0
    No statistical analyses for this end point

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

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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 [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 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Percentage of participants
    number (not applicable)
        Week 24
    14.7
    20.2
    28.2
        Week 52
    18.2
    18.7
    31.2
    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 placebo switched arms

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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 [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 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Percentage of participants
    number (not applicable)
        Week 24
    10.8
    14.8
    12
        Week 52
    11.0
    11.8
    15.5
    No statistical analyses for this end point

    Secondary: Percentage of participants achieving a good/moderate (European League Against Rheumatism) EULAR response at Week 12

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    End point title
    		 Percentage of participants achieving a good/moderate (European League Against Rheumatism) EULAR response at Week 12 [27]
    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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
        number (not applicable)
    73.1
    69.3
    83.0
    54.5
    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

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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 [28]
    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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
    number (not applicable)
        Week 24
    78.4
    74.9
    89.8
        Week 52
    79.1
    78.6
    89.0
    No statistical analyses for this end point

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

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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 [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. 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Percentage of participants
    number (not applicable)
        Week 24
    76.3
    82.4
    88.9
        Week 52
    87.1
    79.1
    92.5
    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

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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 [30]
    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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    453
    467
    227
    Units: Participants
        Week 24
    16
    13
    14
        Week 52
    24
    13
    18
    No statistical analyses for this end point

    Secondary: Number of participants achieving ACR/EULAR remission at Week 12

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    End point title
    		 Number of participants achieving ACR/EULAR remission at Week 12 [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 inlcudes 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    475
    477
    228
    Units: Participants
    11
    9
    11
    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

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    End point title
    		 Number of participants achieving ACR/EULAR remission at Week 24 and Week 52 for placebo switched arms [32]
    End point description
    Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) <= 1, Swollen Joint Count 66 (SJC66) <= 1, high sensitivity C-reactive Protein (hsCRP) <= 1mg/dl and patient's global assessment of disease activity (PtGA) <= 10. 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
    [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 + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    76
    80
    78
    Units: Participants
        Week 24
    2
    4
    3
        Week 52
    3
    3
    8
    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

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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 [33]
    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
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Percentage of participants
        number (not applicable)
    83.8
    82.6
    88.9
    76.7
    No statistical analyses for this end point

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

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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 [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. 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Percentage of participants
    number (not applicable)
        mTSS <= 0.5, Week 24
    79.5
    79.6
    84.6
        mTSS <= 0.5, Week 52
    71.8
    72.8
    79.7
    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

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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 [35]
    End point description
    Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity. No radiographic progression is defined as a change from Baseline in van der Heijde mTSS score of <=0.5. The analysis was performed on all randomized participants who 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Percentage of participants
    number (not applicable)
        mTSS <= 0.5, Week 24
    78.6
    74.6
    77.7
        mTSS <= 0.5, Week 52
    76.0
    68.3
    69.5
    No statistical analyses for this end point

    Secondary: Change from Baseline in CDAI total score at Week 12

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    End point title
    		 Change from Baseline in CDAI total score at Week 12 [36]
    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. 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. The analysis was performed on the ITT set using multiple imputation method to handle missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Scores on a scale
        least squares mean (standard error)
    -17.85 ( 0.574 )
    -17.15 ( 0.563 )
    -21.39 ( 0.801 )
    -13.01 ( 0.798 )
    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

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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 [37]
    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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -20.63 ( 0.561 )
    -19.88 ( 0.551 )
    -24.5 ( 0.781 )
        Week 52
    -21.79 ( 0.558 )
    -21.81 ( 0.549 )
    -25.55 ( 0.77 )
    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

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    End point title
    		 Change from Baseline in CDAI total score at Week 24 and Week 52 for placebo switched arms [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. For efficacy assessments baseline is interpreted as Day 1. 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
    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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -21.41 ( 1.359 )
    -22.93 ( 1.31 )
    -24.5 ( 1.307 )
        Week 52
    -23.49 ( 1.365 )
    -22.91 ( 1.291 )
    -25.83 ( 1.28 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12

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    End point title
    		 Change from Baseline in DAS28-CRP/DAS28-ESR at Week 12 [39]
    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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Scores on a scale
    least squares mean (standard error)
        DAS28-CRP
    -1.49 ( 0.054 )
    -1.44 ( 0.053 )
    -1.96 ( 0.076 )
    -1.01 ( 0.075 )
        DAS28-ESR
    -1.53 ( 0.057 )
    -1.48 ( 0.056 )
    -1.97 ( 0.079 )
    -1.07 ( 0.079 )
    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

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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 [40]
    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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Scores on a scale
    least squares mean (standard error)
        DAS28-CRP, Week 24
    -1.74 ( 0.056 )
    -1.67 ( 0.055 )
    -2.31 ( 0.078 )
        DAS28-CRP, Week 52
    -1.85 ( 0.06 )
    -1.82 ( 0.059 )
    -2.39 ( 0.083 )
        DAS28-ESR, Week 24
    -1.79 ( 0.059 )
    -1.74 ( 0.057 )
    -2.3 ( 0.082 )
        DAS28-ESR, Week 52
    -1.92 ( 0.063 )
    -1.84 ( 0.062 )
    -2.36 ( 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

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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 [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 efficacy assessments baseline is interpreted as Day 1. 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
    Baseline (Day 1), Week 24 and Week 52
    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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Scores on a scale
    least squares mean (standard error)
        DAS28-CRP, Week 24
    -1.77 ( 0.136 )
    -1.95 ( 0.131 )
    -2.29 ( 0.131 )
        DAS28-CRP, Week 52
    -1.92 ( 0.146 )
    -1.96 ( 0.139 )
    -2.37 ( 0.137 )
        DAS28-ESR, Week 24
    -1.84 ( 0.143 )
    -2.05 ( 0.137 )
    -2.23 ( 0.137 )
        DAS28-ESR, Week 52
    -2.06 ( 0.151 )
    -2.06 ( 0.145 )
    -2.43 ( 0.145 )
    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

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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 [42]
    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
    [42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    0.25 ( 0.08 )
    0.38 ( 0.078 )
    0.2 ( 0.112 )
        Week 52
    0.61 ( 0.117 )
    0.63 ( 0.114 )
    0.35 ( 0.158 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Van der Heijde mTSS at Week 12

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    End point title
    		 Change from Baseline in Van der Heijde mTSS at Week 12 [43]
    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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Scores on a scale
        least squares mean (standard error)
    0.15 ( 0.075 )
    0.19 ( 0.073 )
    0.13 ( 0.104 )
    0.55 ( 0.103 )
    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

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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 [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 efficacy assessments baseline is interpreted as Day 1. 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
    Baseline (Day 1), Week 24 and Week 52
    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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    0.71 ( 0.215 )
    0.77 ( 0.208 )
    0.67 ( 0.208 )
        Week 52
    0.9 ( 0.309 )
    1.24 ( 0.306 )
    1.06 ( 0.297 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in HAQ-DI at Week 24 and Week 52 for placebo switched arms [45]
    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 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
    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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -0.53 ( 0.065 )
    -0.46 ( 0.062 )
    -0.58 ( 0.062 )
        Week 52
    -0.47 ( 0.069 )
    -0.45 ( 0.066 )
    -0.67 ( 0.065 )
    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

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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 [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), Week 24 and Week 52
    Notes
    [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -0.51 ( 0.027 )
    -0.41 ( 0.026 )
    -0.56 ( 0.037 )
        Week 52
    -0.54 ( 0.028 )
    -0.46 ( 0.028 )
    -0.58 ( 0.039 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Arthritis pain VAS at Week 12

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    End point title
    		 Change from Baseline in Arthritis pain VAS at Week 12 [47]
    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
    [47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Scores on a scale
        least squares mean (standard error)
    -22 ( 1.056 )
    -19.56 ( 1.033 )
    -27.26 ( 1.473 )
    -14.58 ( 1.466 )
    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

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    End point title
    		 Change from Baseline in Arthritis pain VAS at Week 24 and Week 52 for placebo switched arms [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 efficacy assessments baseline is interpreted as Day 1. 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
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -26.91 ( 2.666 )
    -28.02 ( 2.564 )
    -29.13 ( 2.566 )
        Week 52
    -24.08 ( 2.902 )
    -29.22 ( 2.765 )
    -34.8 ( 2.742 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Short form (SF)-36 physical component scores (PCS) at Week 12 [49]
    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
    [49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: T-Score
        least squares mean (standard error)
    5.38 ( 0.305 )
    4.96 ( 0.297 )
    6.93 ( 0.427 )
    3.19 ( 0.423 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 mental component scores (MCS) at Week 12 [50]
    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
    [50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: T-Score
        least squares mean (standard error)
    2.88 ( 0.41 )
    2.54 ( 0.399 )
    4.04 ( 0.574 )
    2.46 ( 0.569 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 domain scores at Week 12

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    End point title
    		 Change from Baseline in SF-36 domain scores at Week 12 [51]
    End point description
    SF-36 survey assessed health-related quality of life, covering physical functioning, bodily pain, role limitations due to physical/emotional issues, general health, mental health, social functioning, and vitality. MCS consists of four domains (MH, vitality, SF, role-emotional), and PCS consists of four domains (PF, role-physical, BP, GH).Individual question items were totaled within items under various sections, and these domain scores were then scaled from 0 to 100, with higher scores indicating better health. Positive changes from the baseline indicated improvements. Scoring of SF-36 utilized Quality Metric software. Baseline=latest pre-dose assessment with NMV, including those from unscheduled visits. CB=subtracting PD visit value from BV. For analysis up to week 12, placebo arms were pooled into single arm to serve as reference for active treatment arm comparison. ITT set was analyzed only those participants with data available at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    474
    483
    235
    Units: Scores on a scale
    arithmetic mean (standard error)
        Bodily Pain
    15.21 ( 21.448 )
    14.65 ( 21.208 )
    20.83 ( 22.432 )
        General Health
    8.23 ( 15.662 )
    7.32 ( 15.462 )
    11.11 ( 16.447 )
        Mental Health
    7.03 ( 18.222 )
    6.4 ( 18.993 )
    10.19 ( 18.659 )
        Physical Function
    13.2 ( 21.092 )
    12.9 ( 21.564 )
    17.81 ( 19.957 )
        Role Emotional
    7.47 ( 25.231 )
    7.35 ( 25.162 )
    9.25 ( 25.836 )
        Role Physical
    12.51 ( 21.751 )
    12.56 ( 23.345 )
    16.28 ( 22.117 )
        Social Function
    9.2 ( 23.558 )
    8.72 ( 26.227 )
    14.15 ( 25.092 )
        Vitality
    11.05 ( 20.216 )
    9.82 ( 19.662 )
    14.63 ( 20.185 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 PCS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

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    End point title
    		 Change from Baseline in SF-36 PCS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 [52]
    End point description
    SF-36 survey evaluates health-related quality of life, covering physical functioning(PF), bodily pain(BP), role limitations due to physical/emotional issues, general health(GH), MH, SF, vitality. Each domains is scored using average, 0-100; higher score represents better health. PCS was aggregated across domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. PCS is primarily derived from 4 domains(PF, role-physical, BP, GH) representing overall physical health. Positive change from baseline, reported using T-score change, indicates improvement in overall physical health. Quality Metric software was used for scoring. Baseline was defined as latest pre-dose assessment with a non-missing value, including from unscheduled visits. Change from Baseline was calculated by subtracting post dose value from Baseline value. ITT set was analyzed using multiple imputation to manage missing data.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    Notes
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: T-Score
    least squares mean (standard error)
        Week 24
    6.26 ( 0.319 )
    5.82 ( 0.313 )
    8.07 ( 0.448 )
        Week 52
    6.5 ( 0.364 )
    6.04 ( 0.358 )
    8.23 ( 0.507 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 MCS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

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    End point title
    		 Change from Baseline in SF-36 MCS at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 [53]
    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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: T-Score
    least squares mean (standard error)
        Week 24
    3.69 ( 0.401 )
    3.87 ( 0.393 )
    2.92 ( 0.563 )
        Week 52
    3.13 ( 0.443 )
    2.75 ( 0.437 )
    3.53 ( 0.616 )
    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

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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 [54]
    End point description
    SF-36 survey assessed health-related quality of life, covering physical functioning, bodily pain, role limitations due to physical/emotional issues, general health, mental health, social functioning, and vitality. MCS consists of four domains (MH,vitality,SF,role-emotional), and PCS consists of four domains (PF,role-physical,BP,GH).Individual question items were totaled within items under various sections, and these domain scores were then scaled from 0 to 100, with higher scores indicating better health. Positive changes from the baseline indicated improvements. Scoring of SF-36 utilized Quality Metric software. Baseline was defined as most recent pre-dose non-missing value, including unscheduled visits. Change from baseline was calculated by subtracting post dose value from Baseline value. Analysis was performed on all randomized participants who received study intervention from Day01 to Week52. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 24 and Week 52
    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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    459
    469
    227
    Units: Scores on a scale
    arithmetic mean (standard error)
        Bodily Pain, Week 24
    18.8 ( 21.717 )
    18.06 ( 21.303 )
    23.07 ( 22.7 )
        Bodily Pain, Week 52
    18.93 ( 23.084 )
    18.39 ( 22.667 )
    24.87 ( 23.427 )
        General Health, Week 24
    9.7 ( 15.747 )
    9.01 ( 15.577 )
    11.46 ( 16.416 )
        General Health, Week 52
    10.2 ( 16.795 )
    8.81 ( 17.426 )
    12.4 ( 19.371 )
        Mental Health, Week 24
    9.14 ( 17.511 )
    8.88 ( 19.515 )
    9.89 ( 18.461 )
        Mental Health, Week 52
    8.65 ( 18.468 )
    7.43 ( 20.048 )
    10.44 ( 21.685 )
        Physical Function, Week 24
    16.35 ( 22.51 )
    16.2 ( 23.122 )
    20.9 ( 21.808 )
        Physical Function, Week 52
    16.18 ( 24.737 )
    17.22 ( 23.464 )
    21.77 ( 25.534 )
        Role Emotional, Week 24
    10.75 ( 25.123 )
    10.54 ( 25.451 )
    7.86 ( 25.124 )
        Role Emotional, Week 52
    10.08 ( 26.113 )
    9.24 ( 26.689 )
    9.3 ( 26.279 )
        Role Physical, Week 24
    15.35 ( 22.432 )
    14.87 ( 23.361 )
    18.81 ( 22.588 )
        Role Physical, Week 52
    16.5 ( 23.981 )
    14.74 ( 24.325 )
    19.16 ( 24.391 )
        Social Function, Week 24
    11.6 ( 23.543 )
    12.95 ( 26.72 )
    13.49 ( 24.164 )
        Social Function, Week 52
    11.66 ( 25.523 )
    10.51 ( 26.367 )
    15.29 ( 24.872 )
        Vitality, Week 24
    13.37 ( 19.908 )
    13.02 ( 20.115 )
    15.5 ( 19.854 )
        Vitality, Week 52
    13.37 ( 20.358 )
    12.23 ( 20.712 )
    15.73 ( 21.767 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 PCS at Week 24 and Week 52 for placebo switched arms

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    End point title
    		 Change from Baseline in SF-36 PCS at Week 24 and Week 52 for placebo switched arms [55]
    End point description
    SF-36 survey evaluates health-related quality of life, covering physical functioning(PF), bodily pain(BP), role limitations due to physical/emotional issues, general health(GH), 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: T-Score
    least squares mean (standard error)
        Week 24
    6.31 ( 0.773 )
    7.07 ( 0.746 )
    8.21 ( 0.747 )
        Week 52
    5.68 ( 0.89 )
    6.27 ( 0.852 )
    8.81 ( 0.848 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 MCS at Week 24 and Week 52 for placebo switched arms

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    End point title
    		 Change from Baseline in SF-36 MCS at Week 24 and Week 52 for placebo switched arms [56]
    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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: T-Score
    least squares mean (standard error)
        Week 24
    3.76 ( 0.973 )
    4.43 ( 0.938 )
    4.2 ( 0.942 )
        Week 52
    3.06 ( 1.081 )
    3.77 ( 1.032 )
    5.47 ( 1.027 )
    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

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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 [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, 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    75
    81
    80
    Units: Scores on a scale
    arithmetic mean (standard error)
        Bodily Pain, Week 24
    20.13 ( 23.373 )
    23.28 ( 20.682 )
    22.23 ( 20.389 )
        Bodily Pain, Week 52
    21.00 ( 24.696 )
    24.96 ( 22.495 )
    26.68 ( 22.838 )
        General Health, Week 24
    9.6 ( 18.212 )
    12.02 ( 15.209 )
    9.44 ( 13.61 )
        General Health, Week 52
    9.46 ( 16.95 )
    9.00 ( 15.591 )
    9.38 ( 15.469 )
        Mental Health, Week 24
    8.67 ( 18.405 )
    9.81 ( 16.21 )
    6.94 ( 16.41 )
        Mental Health, Week 52
    9.55 ( 22.271 )
    9.87 ( 18.214 )
    9.14 ( 17.576 )
        Physical Function, Week 24
    18.2 ( 20.725 )
    21.42 ( 24.94 )
    20.69 ( 22.385 )
        Physical Function, Week 52
    15.6 ( 25.13 )
    18.87 ( 26.655 )
    22.89 ( 20.22 )
        Role Emotional, Week 24
    12.89 ( 27.478 )
    14.71 ( 24.73 )
    10.83 ( 26.131 )
        Role Emotional, Week 52
    10.07 ( 28.705 )
    13.11 ( 29.612 )
    13.92 ( 28.231 )
        Role Physical, Week 24
    17.83 ( 24.739 )
    17.36 ( 24.065 )
    17.58 ( 19.053 )
        Role Physical, Week 52
    18.38 ( 25.35 )
    17.08 ( 26.443 )
    21.05 ( 19.144 )
        Social Function, Week 24
    16.83 ( 21.503 )
    16.36 ( 22.504 )
    15.47 ( 23.804 )
        Social Function, Week 52
    16.6 ( 25.505 )
    14.00 ( 25.165 )
    20.56 ( 25.389 )
        Vitality, Week 24
    15.92 ( 19.176 )
    18.36 ( 19.196 )
    15.31 ( 17.731 )
        Vitality, Week 52
    16.14 ( 19.769 )
    16.42 ( 17.671 )
    16.12 ( 19.345 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in Functional assessment of chronic illness therapy (FACIT)-Fatigue at Week 12 [58]
    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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    258
    256
    Units: Scores on a scale
        least squares mean (standard error)
    7.07 ( 0.41 )
    6.3 ( 0.399 )
    8.28 ( 0.577 )
    4.72 ( 0.57 )
    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

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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 [59]
    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), 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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    -25.43 ( 1.096 )
    -22.56 ( 1.069 )
    -31.02 ( 1.53 )
        Week 52
    -28.36 ( 1.188 )
    -25.22 ( 1.175 )
    -33.34 ( 1.646 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in FACIT-Fatigue at Week 24 and Week 52 for placebo switched arms [60]
    End point description
    The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life. A positive change from baseline in FACIT-fatigue indicates an improvement. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For efficacy assessments baseline is interpreted as Day 1. Participants who received study intervention from Week 12 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
    [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 + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    85
    86
    85
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    7.57 ( 1.002 )
    7.91 ( 0.965 )
    9.44 ( 0.969 )
        Week 52
    7.08 ( 1.102 )
    7.2 ( 1.051 )
    11.05 ( 1.043 )
    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

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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 [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. 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    258
    Units: Scores on a scale
    least squares mean (standard error)
        Week 24
    8.52 ( 0.418 )
    7.59 ( 0.406 )
    8.56 ( 0.585 )
        Week 52
    7.71 ( 0.453 )
    6.76 ( 0.446 )
    8.55 ( 0.632 )
    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)

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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) [62]
    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. Experimental arms collected data from Day 01 to Week 59.
    End point type
    Secondary
    End point timeframe
    Up to Week 59
    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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    273
    241
    Units: Participants
        AE
    367
    383
    207
    95
        SAE
    33
    39
    23
    8
        AESI
    65
    58
    22
    4
    No statistical analyses for this end point

    Secondary: Change from Baseline in white blood cell (WBC) count at Week 12

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    End point title
    		 Change from Baseline in white blood cell (WBC) count at Week 12 [63]
    End point description
    Blood samples were collected for the assessment of hematology parameter white blood cell count. 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 Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    456
    455
    230
    213
    Units: Giga cells per liter (10^9/L)
        arithmetic mean (standard deviation)
    -0.55 ( 2.267 )
    -0.63 ( 2.065 )
    -1.03 ( 2.16 )
    -0.3 ( 2.005 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in WBC count at Week 24 and Week 52 for treatment arms who started study intervention from Day 1

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    End point title
    		 Change from Baseline in WBC count at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 [64]
    End point description
    Blood samples were collected for the assessment of hematology parameter white blood cell count. 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 Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    443
    465
    246
    Units: Giga cells per liter (10^9/L)
    arithmetic mean (standard deviation)
        Week 24
    -0.59 ( 2.279 )
    -0.5 ( 2.123 )
    -0.94 ( 2.31 )
        Week 52
    -0.54 ( 2.386 )
    -0.52 ( 2.051 )
    -1.21 ( 2.407 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in WBC count at Week 24 and Week 52 for placebo switched arms

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    End point title
    		 Change from Baseline in WBC count at Week 24 and Week 52 for placebo switched arms [65]
    End point description
    Blood samples were collected for the assessment of hematology parameter white blood cell count. 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    78
    78
    63
    Units: Giga cells per liter (10^9/L)
    arithmetic mean (standard deviation)
        Week 24
    -0.06 ( 1.94 )
    -0.31 ( 1.642 )
    -0.61 ( 2.052 )
        Week 52
    -0.21 ( 2.129 )
    -0.03 ( 2.459 )
    -0.96 ( 2.013 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 12

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    End point title
    		 Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 12 [66]
    End point description
    Blood samples were collected for the assessment of hematology parameters including 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 Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    453
    454
    229
    211
    Units: Giga cells per liter (10^9/L)
    arithmetic mean (standard deviation)
        Lymphocytes
    0.006 ( 0.5341 )
    0.016 ( 0.5552 )
    0.084 ( 0.5789 )
    -0.009 ( 0.5367 )
        Neutrophils
    -0.565 ( 2.2309 )
    -0.66 ( 2.0562 )
    -1.076 ( 2.162 )
    -0.268 ( 2.025 )
        Platelets
    -18.6 ( 58.93 )
    -16.3 ( 59.51 )
    -26.7 ( 63.56 )
    -1.0 ( 58.79 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 24 and Week 52 for treatment arms who started study intervention from Day 1 [67]
    End point description
    Blood samples were collected for the assessment of hematology parameters including 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 the Safety Set. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    442
    464
    246
    Units: Giga cells per liter (10^9/L)
    arithmetic mean (standard deviation)
        Lymphocytes, Week 24
    0.031 ( 0.583 )
    -0.003 ( 0.5395 )
    0.017 ( 0.62 )
        Lymphocytes, Week 52
    0.015 ( 0.5485 )
    -0.034 ( 0.5771 )
    -0.102 ( 0.5877 )
        Neutrophils, Week 24
    -0.629 ( 2.2736 )
    -0.515 ( 1.9997 )
    -0.899 ( 2.2436 )
        Neutrophils, Week 52
    -0.583 ( 2.3708 )
    -0.493 ( 1.9958 )
    -1.049 ( 2.3054 )
        Platelets, Week 24
    -13.7 ( 65.69 )
    -15.4 ( 67.72 )
    -27.1 ( 70.17 )
        Platelets, Week 52
    -18.7 ( 66.07 )
    -18.5 ( 64.59 )
    -30.2 ( 56.67 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 24 and Week 52 for placebo switched arms

    		 Close Top of page
    End point title
    		 Change from Baseline in hematology parameter of platelet count, neutrophils, lymphocytes at Week 24 and Week 52 for placebo switched arms [68]
    End point description
    Blood samples were collected for the assessment of hematology parameters including 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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    78
    78
    63
    Units: Giga cells per liter (10^9/L)
    arithmetic mean (standard deviation)
        Lymphocytes, Week 24
    -0.055 ( 0.5751 )
    0.038 ( 0.5294 )
    0.085 ( 0.5052 )
        Lymphocytes, Week 52
    -0.091 ( 0.6046 )
    0.09 ( 0.5744 )
    -0.079 ( 0.4538 )
        Neutrophils, Week 24
    -0.053 ( 1.8784 )
    -0.405 ( 1.5633 )
    -0.685 ( 1.9031 )
        Neutrophils, Week 52
    -0.118 ( 2.0773 )
    -0.289 ( 2.3914 )
    -0.847 ( 1.8472 )
        Platelets, Week 24
    -11.3 ( 59.64 )
    -17.4 ( 63.81 )
    -9.3 ( 43.83 )
        Platelets, Week 52
    -19 ( 65.35 )
    -11.7 ( 86.52 )
    -19.6 ( 51.16 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in hematology parameter of hemoglobin at Week 12

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    End point title
    		 Change from Baseline in hematology parameter of hemoglobin at Week 12 [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. 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 participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    457
    459
    231
    214
    Units: Grams per liter (g/L)
        arithmetic mean (standard deviation)
    -0.0 ( 8.14 )
    0.5 ( 8.5 )
    0.0 ( 8.56 )
    -1.7 ( 7.83 )
    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

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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 [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 + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    78
    78
    63
    Units: Grams per liter (g/L)
    arithmetic mean (standard deviation)
        Week 24
    0.7 ( 8.72 )
    2 ( 9.02 )
    1.8 ( 6.71 )
        Week 52
    1.4 ( 9.85 )
    1.1 ( 10.57 )
    0.8 ( 8.81 )
    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

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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 [71]
    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 participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    444
    466
    246
    Units: Grams per liter (g/L)
    arithmetic mean (standard deviation)
        Week 24
    0.5 ( 8.96 )
    1.3 ( 9.22 )
    1.1 ( 9.23 )
        Week 52
    0.4 ( 9.5 )
    0.7 ( 9.24 )
    -0.2 ( 9.14 )
    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

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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 [72]
    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 participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    468
    475
    242
    220
    Units: International units per liter (IU/L)
    arithmetic mean (standard deviation)
        Alkaline Phosphatase
    -1.5 ( 17.97 )
    -1.2 ( 15.64 )
    -3.7 ( 16.07 )
    -0.7 ( 15.29 )
        ALT
    0.5 ( 15.69 )
    2 ( 19.66 )
    2.2 ( 15.07 )
    -1.1 ( 11.76 )
        AST
    1.2 ( 9.71 )
    2.4 ( 13.09 )
    3.1 ( 14.09 )
    -0.4 ( 7.38 )
        Gamma Glutamyl Transferase
    -2.1 ( 17.67 )
    -2.3 ( 16.05 )
    1.2 ( 23.21 )
    -0.5 ( 16.31 )
    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

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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 [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. The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    448
    467
    246
    Units: International units per liter (IU/L)
    arithmetic mean (standard deviation)
        Alkaline Phosphatase, Week 24
    0.5 ( 17.77 )
    1.8 ( 19.16 )
    -3.0 ( 17.41 )
        Alkaline Phosphatase, Week 52
    2.8 ( 19.52 )
    1.5 ( 17.35 )
    -1.0 ( 18.12 )
        ALT, Week 24
    1.5 ( 22.98 )
    2.5 ( 17.22 )
    4.5 ( 40.51 )
        ALT, Week 52
    0.4 ( 12.31 )
    -0.2 ( 13.95 )
    1.9 ( 15.72 )
        AST, Week 24
    1.3 ( 11.36 )
    2.4 ( 11.25 )
    8.6 ( 94.12 )
        AST, Week 52
    1 ( 8.97 )
    1 ( 8.22 )
    3.1 ( 14.21 )
        Gamma Glutamyl Transferase, Week 24
    -1.7 ( 18.05 )
    -1.2 ( 17.71 )
    0.2 ( 19.7 )
        Gamma Glutamyl Transferase, Week 52
    -0.3 ( 22.26 )
    -0.4 ( 22.03 )
    1.6 ( 20.52 )
    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

    		 Close Top of page
    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 [74]
    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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    78
    78
    63
    Units: International units per liter (IU/L)
    arithmetic mean (standard deviation)
        Alkaline Phosphatase, Week 24
    0.9 ( 13.07 )
    -0.3 ( 18.04 )
    0.7 ( 14.91 )
        Alkaline Phosphatase, Week 52
    5.5 ( 24.05 )
    -1.9 ( 16.07 )
    -1 ( 14.6 )
        ALT, Week 24
    0.3 ( 10.76 )
    3.6 ( 18.43 )
    3.3 ( 13.9 )
        ALT, Week 52
    2.6 ( 15.59 )
    2.6 ( 11.55 )
    2.7 ( 15.03 )
        AST, Week 24
    1.5 ( 11.4 )
    2.9 ( 13.53 )
    3.2 ( 10.53 )
        AST, Week 52
    1.8 ( 6.89 )
    2 ( 9.08 )
    3.6 ( 9.88 )
        Gamma Glutamyl Transferase, Week 24
    0.8 ( 13.65 )
    0.9 ( 16.68 )
    -0.5 ( 32.46 )
        Gamma Glutamyl Transferase, Week 52
    8.1 ( 55.51 )
    1 ( 14.4 )
    -2.2 ( 35.14 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in clinical chemistry parameter of total bilirubin at Week 12

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    End point title
    		 Change from Baseline in clinical chemistry parameter of total bilirubin at Week 12 [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. 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 participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    468
    475
    242
    220
    Units: Micromoles per liter (umol/L)
        arithmetic mean (standard deviation)
    0.3 ( 2.63 )
    0.4 ( 2.52 )
    0.5 ( 2.96 )
    -0.2 ( 3.13 )
    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

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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 [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. The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    448
    467
    246
    Units: Micromoles per liter (umol/L)
    arithmetic mean (standard deviation)
        Week 24
    0.5 ( 2.93 )
    0.6 ( 2.79 )
    0.6 ( 2.95 )
        Week 52
    0.5 ( 2.73 )
    0.4 ( 2.81 )
    0.5 ( 3.2 )
    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

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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 [77]
    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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    78
    78
    63
    Units: Micromoles per liter (umol/L)
    arithmetic mean (standard deviation)
        Week 24
    0.2 ( 2.65 )
    0.6 ( 2.8 )
    0.1 ( 2.62 )
        Week 52
    0.3 ( 3.16 )
    0.6 ( 2.75 )
    0.6 ( 2.64 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in clinical chemistry parameter of albumin at Week 12

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    End point title
    		 Change from Baseline in clinical chemistry parameter of albumin at Week 12 [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. 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 participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    468
    475
    242
    220
    Units: Grams per liter (g/L)
        arithmetic mean (standard deviation)
    -0.2 ( 2.7 )
    0.2 ( 2.53 )
    0.8 ( 3.05 )
    -0.7 ( 2.7 )
    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

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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 [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. The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    448
    466
    246
    Units: Grams per liter (g/L)
    arithmetic mean (standard deviation)
        Week 24
    0.2 ( 2.85 )
    0.3 ( 2.69 )
    1.3 ( 3.17 )
        Week 52
    -0.2 ( 3.08 )
    0.3 ( 3.03 )
    0.6 ( 2.83 )
    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

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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 [80]
    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
    [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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    78
    78
    63
    Units: Grams per liter (g/L)
    arithmetic mean (standard deviation)
        Week 24
    0.3 ( 2.57 )
    1.1 ( 2.54 )
    1.8 ( 2.47 )
        Week 52
    0.3 ( 2.94 )
    0.8 ( 2.77 )
    1.2 ( 2.24 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in lipid profile parameter of total cholesterol at Week 12

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    End point title
    		 Change from Baseline in lipid profile parameter of total cholesterol at Week 12 [81]
    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 activities 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 profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 4. Week 4 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    0 [82]
    0 [83]
    0 [84]
    0 [85]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [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.
    [85] - 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

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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 [86]
    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 activities 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 profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    0 [87]
    0 [88]
    0 [89]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [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.
    [89] - 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

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    End point title
    		 Change from Baseline in lipid profile parameter of total cholesterol at Week 24 for placebo switched arms [90]
    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 activities 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 profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [90] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    0 [91]
    0 [92]
    0 [93]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [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.
    [93] - 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

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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 [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. The analysis was performed on the Safety Set participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    394
    405
    223
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    0.084 ( 0.846 )
    0.074 ( 0.9528 )
    0.535 ( 0.9012 )
    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

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    End point title
    		 Change from Baseline in lipid profile parameter of total cholesterol at Week 52 for placebo switched arms [95]
    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 (Day 1) and Week 52
    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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    62
    69
    56
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    0.334 ( 0.7608 )
    0.045 ( 0.7931 )
    0.486 ( 0.8974 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol at Week 12 [96]
    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 reference for comparison of active treatment arms. Blood samples were collected at indicated time points per schedule of activities 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 profile, there is no corresponding time point in schedule of activities. Consequently, objective cannot be assessed at the specified time points since sample was collected at Week 4. Week 4 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    0 [97]
    0 [98]
    0 [99]
    0 [100]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [97] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [98] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [99] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [100] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

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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 [101]
    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 activities 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 profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [101] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    0 [102]
    0 [103]
    0 [104]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [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.
    [104] - 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

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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 [105]
    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 activities 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 profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [105] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    0 [106]
    0 [107]
    0 [108]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [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.
    [108] - 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

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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 [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 participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [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
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    394
    405
    223
    Units: Millimoles per liter (mmol/L)
    arithmetic mean (standard deviation)
        HDL Cholesterol, Direct
    -0.046 ( 0.3024 )
    0.011 ( 0.2887 )
    0.117 ( 0.2986 )
        LDL Cholesterol
    0.089 ( 0.7062 )
    0.053 ( 0.736 )
    0.369 ( 0.758 )
    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

    		 Close Top of page
    End point title
    		 Change from Baseline in lipid profile parameter of LDL cholesterol, high-density lipoprotein-cholesterol at Week 52 for placebo switched arms [110]
    End point description
    Blood samples were collected for the assessment of fasting lipid profile including LDL cholesterol, HDL cholesterol levels. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value. For safety assessments baseline is interpreted as Week 12. The analysis was performed on the Safety Set. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 52
    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
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    62
    69
    56
    Units: Millimoles per liter (mmol/L)
    arithmetic mean (standard deviation)
        HDL Cholesterol, Direct
    0.083 ( 0.302 )
    0.033 ( 0.209 )
    0.092 ( 0.2701 )
        LDL Cholesterol
    0.221 ( 0.6669 )
    -0.003 ( 0.697 )
    0.304 ( 0.8315 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in lipid profile parameter of triglycerides at Week 12

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    End point title
    		 Change from Baseline in lipid profile parameter of triglycerides at Week 12 [111]
    End point description
    Blood samples was collected for 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 post dose visit value from Baseline value. For purpose of all analyses up to week 12, the placebo arms were pooled into a single placebo arm to primarily serve as reference for comparison of active treatment arms. Blood samples were collected at indicated time points per schedule of activities 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 profile, there is no corresponding time point in schedule of activities. Consequently, objective cannot be assessed at the specified time points since sample was collected at Week 4. Week 4 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 12
    Notes
    [111] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    0 [112]
    0 [113]
    0 [114]
    0 [115]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [112] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [113] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [114] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [115] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

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

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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 [116]
    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 activities 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 profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [116] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    0 [117]
    0 [118]
    0 [119]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [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.
    [119] - 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

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    End point title
    		 Change from Baseline in lipid profile parameter of triglycerides at Week 24 for placebo switched arms [120]
    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 activities 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 profile, there is no corresponding time point in schedule of activities. Consequently, the objective cannot be assessed at the specified time points since the sample was collected at Week 16. Week 16 is not pre-specified time point to report.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 24
    Notes
    [120] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing 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 + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    0 [121]
    0 [122]
    0 [123]
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [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.
    [123] - 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

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    End point title
    		 Change from Baseline in lipid profile parameter of triglycerides at Week 52 for treatment arms who started study intervention from Day 1 [124]
    End point description
    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 participants. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled 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
    [124] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    394
    405
    223
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    0.081 ( 0.5531 )
    0.051 ( 0.7413 )
    0.119 ( 0.7325 )
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in lipid profile parameter of triglycerides at Week 52 for placebo switched arms [125]
    End point description
    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 (Day 1) and Week 52
    Notes
    [125] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    62
    69
    56
    Units: Millimoles per liter (mmol/L)
        arithmetic mean (standard deviation)
    0.066 ( 0.5071 )
    0.03 ( 0.6306 )
    0.241 ( 0.5357 )
    No statistical analyses for this end point

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

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    End point title
    		 Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE) >=Grade 3 hematological/clinical chemistry abnormalities [126]
    End point description
    Number of participants with NCI-CTCAE >=Grade 3 hematological/clinical chemistry abnormalities were summarized. Hematological and Clinical chemistry parameters were summarized according to the NCI-CTCAE, version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Data is presented for only those parameters for which participants had worst case >=Grade 3 shifts from Baseline. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. The analysis was performed on the Safety Set that includes all randomized participants who received at least one dose of study treatment. Pooled Placebo collected data till Week 12. Placebo switched arms collected data from Week 12 to 59. Experimental arm collected data from Day 01 to Week 59.
    End point type
    Secondary
    End point timeframe
    Up to Week 59
    Notes
    [126] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo
    Number of subjects analysed
    513
    510
    273
    241
    Units: Participants
        Aspartate aminotransferase increased,Total,Grade 3
    0
    5
    1
    0
        Aspartate aminotransferase increased,Total,Grade 4
    0
    0
    1
    0
        Hypertriglyceridemia, Total, Grade 3
    2
    1
    2
    1
        Hypertriglyceridemia, Total, Grade 4
    1
    1
    0
    0
        Neutrophil count decreased, Grade 3, Grade 4
    0
    0
    0
    0
        Neutrophil count decreased, Grade 4, Grade 3
    0
    0
    0
    0
        Alanine aminotransferase increased, Total, Grade 3
    5
    6
    1
    0
        Alanine aminotransferase increased, Total, Grade 4
    0
    1
    0
    0
        Blood bilirubin increased, Total, Grade 3
    0
    1
    0
    0
        Cholesterol - high, Total, Grade 3
    0
    1
    0
    0
        Creatinine increased, Total, Grade 3
    0
    1
    0
    0
        Chronic Kidney Disease, Total Grade 3
    2
    2
    1
    0
        Chronic Kidney Disease, Total Grade 4
    0
    1
    0
    0
        Anemia, Total, Grade 3
    2
    4
    1
    0
        White blood cell decreased, Total , Grade 3
    1
    1
    0
    0
        Lymphocyte count decreased, Total, Grade 3
    6
    9
    5
    1
        Lymphocyte count decreased, Total, Grade 4
    0
    1
    0
    0
        Neutrophil count decreased, Total, Grade 3
    4
    0
    0
    2
        Neutrophil count decreased, Total, Grade 4
    2
    3
    1
    1
        Platelet count decreased, Total Grade 3
    1
    0
    0
    0
        Platelet count decreased, Total, Grade 4
    0
    0
    1
    0
    No statistical analyses for this end point

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

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    End point title
    		 Concentrations of Granulocyte-macrophage colony stimulating factor (GM-CSF) autoantibody [127]
    End point description
    Concentrations of GM-CSF autoantibodies were determined. The analysis was performed on the Safety Set. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis. Only those participants with data available at the specified time points were analyzed.
    End point type
    Secondary
    End point timeframe
    At baseline
    Notes
    [127] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    491
    486
    82
    85
    70
    264
    Units: Microgram per liter (ug/L)
        arithmetic mean (standard deviation)
    832.827 ( 12355.2805 )
    218.456 ( 632.5733 )
    231.376 ( 446.1713 )
    357.087 ( 629.3471 )
    240.109 ( 624.4536 )
    203.31 ( 444.708 )
    No statistical analyses for this end point

    Secondary: Number of participants with anti-GSK3196165 antibodies

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    End point title
    		 Number of participants with anti-GSK3196165 antibodies [128]
    End point description
    Serum samples were collected for determination of anti-GSK3196165 antibodies (ADA) using a validated electrochemiluminescence (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for specificity using the confirmation assay. Samples that confirmed positive in confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in sample. Additionally, confirmed positive ADA samples were also tested in a validated neutralizing antibody assay to determine the potential neutralizing activity of ADA. The analysis was performed on the Safety set. Fifteen participants in Pooled placebo group who received active treatment of Tofacitinib from Week 4 instead of Week 12 as planned. They were pooled with the Tofacitinib arm in safety analysis.
    End point type
    Secondary
    End point timeframe
    Up to Week 59
    Notes
    [128] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX Tofacitinib 5mg + MTX
    Number of subjects analysed
    513
    510
    85
    86
    70
    273
    Units: Participants
    7
    7
    0
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) for placebo switched arms

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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) for placebo switched arms [129]
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is any untoward medical occurrence that, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity and/or can result in death. The analysis was performed on Safety Set of switched arms that collected data from Week 12 to 59.
    End point type
    Secondary
    End point timeframe
    Week 12 to Week 59
    Notes
    [129] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    80
    82
    68
    Units: Participants
        Participants with AE
    49
    52
    44
        Participants with SAE
    8
    9
    5
        Participants with AESI
    9
    9
    3
    No statistical analyses for this end point

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

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    End point title
    		 Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities for placebo switched arms [130]
    End point description
    Number of participants with NCI-CTCAE >=Grade 3 hematological/clinical chemistry abnormalities were summarized. Hematological and Clinical chemistry parameters were summarized according to the NCI-CTCAE, version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Data is presented for only those parameters for which participants had worst case >=Grade 3 shifts from Baseline. The analysis was performed on Safety Set of switched arms that collected data from Week 12 to 59.
    End point type
    Secondary
    End point timeframe
    Week 12 to Week 59
    Notes
    [130] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Number of subjects analysed
    80
    82
    68
    Units: Participants
        Hypertriglyceridemia, Total, Grade 3
    1
    2
    0
        Neutrophil count decreased, Grade 3, Grade 4
    0
    0
    1
        Neutrophil count decreased, Grade 4, Grade 3
    1
    0
    0
        Creatinine increased, Total, Grade 3
    1
    0
    0
        Chronic Kidney Disease, Total Grade 3
    2
    0
    0
        Anemia, Total, Grade 3
    1
    2
    0
        White blood cell decreased, Total, Grade 3
    1
    0
    0
        White blood cell decreased, Total , Grade 3
    0
    0
    1
        Lymphocyte count decreased, Total, Grade 4
    0
    1
    0
        Neutrophil count decreased, Total, Grade 3
    2
    0
    0
        Neutrophil count decreased, Total, Grade 4
    0
    0
    2
        Platelet count decreased, Total Grade 3
    0
    0
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The Pooled Placebo arm collected during the timeframe Week 0 to Week 12. Placebo switched to active treatment arms collected during the timeframe Week 12 to Week 59. Experimental arms collected during from Week 0 to Week 59.
    Adverse event reporting additional description
    The analysis was performed on the Safety Set for pooled placebo and experimental arms. The analysis was performed on Safety Set-Period 2 for placebo switched arms.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    GSK3196165 90mg + MTX
    Reporting group description
    		 Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with methotrexate (MTX).

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

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

    Reporting group title
    Pooled Placebo
    Reporting group description
    		 Participants received Placebo weekly SC injection in combination with MTX until Week 12. The placebo arms are pooled into a single placebo arm.

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

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

    Reporting group title
    Placebo + MTX and Tofacitinib 5mg + MTX
    Reporting group description
    		 Participants received Placebo tablet weekly in combination with MTX for 12 weeks. At Week 12, participants were switched from placebo tablet to Tofacitinib 5mg, capsule, orally, BID in combination with MTX plus placebo injection to maintain the blind for 52 weeks.

    Serious adverse events
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Total subjects affected by serious adverse events
         subjects affected / exposed
    33 / 513 (6.43%)
    39 / 510 (7.65%)
    23 / 273 (8.42%)
    8 / 241 (3.32%)
    8 / 80 (10.00%)
    9 / 82 (10.98%)
    5 / 68 (7.35%)
         number of deaths (all causes)
    2
    7
    3
    1
    0
    1
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Laryngeal squamous cell carcinoma
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic cancer
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    1 / 82 (1.22%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial adenocarcinoma
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    2 / 273 (0.73%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    1 / 241 (0.41%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Ovarian adenoma
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian fibroma
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancoast's tumour
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    1 / 241 (0.41%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Circulatory collapse
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Death
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    2 / 510 (0.39%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Intermenstrual bleeding
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    1 / 82 (1.22%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Conversion disorder
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    1 / 241 (0.41%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device malfunction
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Forearm fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    1 / 80 (1.25%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural complication
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    1 / 80 (1.25%)
    0 / 82 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    1 / 241 (0.41%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    1 / 241 (0.41%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    2 / 513 (0.39%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    1 / 82 (1.22%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    1 / 82 (1.22%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Headache
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive encephalopathy
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar radiculopathy
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular encephalopathy
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    2 / 510 (0.39%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Meniere's disease
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Optic ischaemic neuropathy
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    1 / 82 (1.22%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis ischaemic
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer perforation
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intussusception
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Chronic hepatitis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic cirrhosis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatorenal failure
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Neurogenic bladder
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    1 / 80 (1.25%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Cushing's syndrome
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Goitre
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 9
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fracture nonunion
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Costochondritis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    1 / 80 (1.25%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovial cyst
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    1 / 80 (1.25%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    2 / 513 (0.39%)
    5 / 510 (0.98%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    2 / 80 (2.50%)
    1 / 82 (1.22%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteochondrosis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    1 / 80 (1.25%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    2 / 513 (0.39%)
    0 / 510 (0.00%)
    2 / 273 (0.73%)
    0 / 241 (0.00%)
    1 / 80 (1.25%)
    1 / 82 (1.22%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Arthritis bacterial
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acinetobacter sepsis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    2 / 510 (0.39%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis infective
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    2 / 273 (0.73%)
    1 / 241 (0.41%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic tonsillitis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis staphylococcal
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    2 / 273 (0.73%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    7 / 513 (1.36%)
    10 / 510 (1.96%)
    4 / 273 (1.47%)
    1 / 241 (0.41%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 10
    0 / 4
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint abscess
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis E
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis intestinal perforated
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    2 / 513 (0.39%)
    3 / 510 (0.59%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    1 / 82 (1.22%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 3
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    1 / 82 (1.22%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    2 / 510 (0.39%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    1 / 273 (0.37%)
    1 / 241 (0.41%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural cellulitis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    1 / 510 (0.20%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection pseudomonas
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection staphylococcal
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 513 (0.19%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemic hyperosmolar nonketotic syndrome
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    1 / 273 (0.37%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 GSK3196165 90mg + MTX GSK3196165 150mg + MTX Tofacitinib 5mg + MTX Pooled Placebo Placebo + MTX and GSK3196165 90mg + MTX Placebo + MTX and GSK3196165 150mg + MTX Placebo + MTX and Tofacitinib 5mg + MTX
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    127 / 513 (24.76%)
    137 / 510 (26.86%)
    83 / 273 (30.40%)
    0 / 241 (0.00%)
    22 / 80 (27.50%)
    29 / 82 (35.37%)
    17 / 68 (25.00%)
    Investigations
    Alanine aminotransferase increased
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    23 / 513 (4.48%)
    31 / 510 (6.08%)
    12 / 273 (4.40%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    0 / 82 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    29
    36
    15
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    4 / 80 (5.00%)
    4 / 82 (4.88%)
    1 / 68 (1.47%)
         occurrences all number
    0
    0
    0
    0
    5
    5
    1
    Lymphopenia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    30 / 513 (5.85%)
    35 / 510 (6.86%)
    16 / 273 (5.86%)
    0 / 241 (0.00%)
    2 / 80 (2.50%)
    2 / 82 (2.44%)
    4 / 68 (5.88%)
         occurrences all number
    54
    50
    20
    0
    2
    3
    4
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    2 / 80 (2.50%)
    8 / 82 (9.76%)
    1 / 68 (1.47%)
         occurrences all number
    0
    0
    0
    0
    2
    8
    1
    Infections and infestations
    COVID-19
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    43 / 513 (8.38%)
    48 / 510 (9.41%)
    29 / 273 (10.62%)
    0 / 241 (0.00%)
    6 / 80 (7.50%)
    9 / 82 (10.98%)
    2 / 68 (2.94%)
         occurrences all number
    44
    48
    29
    0
    6
    9
    3
    Latent tuberculosis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    5 / 80 (6.25%)
    3 / 82 (3.66%)
    1 / 68 (1.47%)
         occurrences all number
    0
    0
    0
    0
    5
    3
    1
    Nasopharyngitis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 513 (0.00%)
    0 / 510 (0.00%)
    0 / 273 (0.00%)
    0 / 241 (0.00%)
    0 / 80 (0.00%)
    2 / 82 (2.44%)
    4 / 68 (5.88%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    4
    Upper respiratory tract infection
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    22 / 513 (4.29%)
    20 / 510 (3.92%)
    18 / 273 (6.59%)
    0 / 241 (0.00%)
    3 / 80 (3.75%)
    4 / 82 (4.88%)
    5 / 68 (7.35%)
         occurrences all number
    23
    23
    22
    0
    4
    5
    6
    Urinary tract infection
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    23 / 513 (4.48%)
    22 / 510 (4.31%)
    19 / 273 (6.96%)
    0 / 241 (0.00%)
    4 / 80 (5.00%)
    0 / 82 (0.00%)
    2 / 68 (2.94%)
         occurrences all number
    26
    26
    23
    0
    5
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 May 2019
    Correction of contraceptive requirements for Women of Child Bearing Potential (WOCBP) and additional clarifications.
    21 Jan 2020
    To detail revised risks, entry and stopping criteria following the update to comparator drug (tofacitinib) label. To introduce new medical device safety reporting wording, required in advance of roll out of pre-filled syringes to this study.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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