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    Clinical Trial Results:
    A 24-week, phase 3, multicentre, randomised, double-blind, efficacy and safety study, comparing GSK3196165 with placebo and with sarilumab, in combination with conventional synthetic DMARDs, in participants with moderately to severely active rheumatoid arthritis who have an inadequate response to biological DMARDs and/or Janus Kinase inhibitors.

    Summary
    EudraCT number
    		 2019-000868-18
    Trial protocol
    		 GB   DE   PL   LT   ES   BE   CZ   HU   IT  
    Global end of trial date
    01 Feb 2022

    Results information
    Results version number
    		 v3(current)
    This version publication date
    03 Aug 2023
    First version publication date
    17 Feb 2023
    Other versions
    		 v1 , v2
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    202018
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    GreatWest Road, Brentford,Middlesex, United Kingdom, TW8 9GS
    Public contact
    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
    15 Mar 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Feb 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare efficacy and safety of GSK3196165 (Otilimab) versus placebo and sarilumab in participants with moderately to severely active rheumatoid arthritis.
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Oct 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: 104
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Czechia: 46
    Country: Number of subjects enrolled
    Germany: 12
    Country: Number of subjects enrolled
    Hungary: 6
    Country: Number of subjects enrolled
    Japan: 38
    Country: Number of subjects enrolled
    Lithuania: 6
    Country: Number of subjects enrolled
    Poland: 108
    Country: Number of subjects enrolled
    South Africa: 11
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 5
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 199
    Worldwide total number of subjects
    550
    EEA total number of subjects
    187
    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)
    419
    From 65 to 84 years
    131
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were randomized in a ratio of 6:6:6:1:1:1 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 12 weeks. Participants randomized to experimental arms from study start received the active intervention for 24 weeks.

    Pre-assignment
    Screening details
    		 Analysis was reported for experimental, and all placebo arms are pooled till Week 12 to serve as reference for comparison. Total 550 participants were randomized; one participant withdrew from 90mg GSK3196165 before receiving intervention due to Protocol Deviation. The participant was removed from intent-to-treat and safety population (N=549).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK3196165 90mg + csDMARD
    Arm description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received GSK3196165 90 mg + csDMARD administered by weekly subcutaneous injection.
    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 + csDMARD
    Arm description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received GSK3196165 150 mg + csDMARD administered by weekly subcutaneous injection.
    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
    		 Sarilumab 200mg + csDMARD
    Arm description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Sarilumab 200 mg + csDMARD administered by subcutaneous injection of sarilumab every other week plus with placebo injection in the intervening weeks to maintain the blind.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Sarilumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received 200mg of Sarilumab once every alternate week.

    Arm title
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD
    Arm description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to(<=)84 years received Placebo +csDMARD until Week 12 later switched toGSK3196165 90 mg +csDMARD administered by weekly subcutaneous injection.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received placebo once every week until Week 12

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received 90mg of GSK3196165once every week from Week 12 to Week 24.

    Arm title
    		 Placebo + csDMARD and GSK3196165 150mg + csDMARD
    Arm description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Placebo + csDMARD until Week 12 later switched to GSK3196165 150 mg + csDMARD administered by weekly subcutaneous injection.
    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 GSK3196165once every week from Week 12 to Week 24.

    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 + csDMARD and Sarilumab 200mg + csDMARD
    Arm description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Placebo + csDMARD until Week 12 later switched to Sarilumab 200mg + csDMARD administered by subcutaneous injection of sarilumab every other week plus with placebo injection in the intervening weeks to maintain the blind.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Sarilumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received 200mg of Sarilumab once every alternate week between Week 12 to Week24

    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 [1]
    		GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Started
    156
    158
    156
    26
    26
    27
    Completed
    143
    144
    133
    23
    25
    26
    Not completed
    13
    14
    23
    3
    1
    1
         Physician decision
    2
    -
    -
    -
    -
    -
         Adverse event, non-fatal
    3
    2
    9
    -
    -
    -
         Informed Consent Withdrawn
    3
    6
    8
    1
    1
    -
         Protocol Deviation
    -
    -
    1
    -
    -
    -
         Investigator Site Closed
    -
    1
    1
    -
    -
    -
         Protocol-Specified Withdrawal Criterion Met
    1
    -
    2
    -
    -
    -
         Lost to follow-up
    1
    2
    1
    -
    -
    1
         Lack of efficacy
    3
    3
    1
    2
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Total 550 participants were randomized; one participant withdrew from 90mg GSK3196165 before receiving intervention due to Protocol Deviation. The participant was removed from intent-to-treat and safety population (N=549)

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    GSK3196165 90mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received GSK3196165 90 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    GSK3196165 150mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received GSK3196165 150 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    Sarilumab 200mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Sarilumab 200 mg + csDMARD administered by subcutaneous injection of sarilumab every other week plus with placebo injection in the intervening weeks to maintain the blind.

    Reporting group title
    Placebo + csDMARD and GSK3196165 90mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to(<=)84 years received Placebo +csDMARD until Week 12 later switched toGSK3196165 90 mg +csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    Placebo + csDMARD and GSK3196165 150mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Placebo + csDMARD until Week 12 later switched to GSK3196165 150 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Placebo + csDMARD until Week 12 later switched to Sarilumab 200mg + csDMARD administered by subcutaneous injection of sarilumab every other week plus with placebo injection in the intervening weeks to maintain the blind.

    Reporting group values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD Total
    Number of subjects
    		 156 158 156 26 26 27 549
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 119 121 115 23 21 19 418
        From 65-84 years
    		 37 37 41 3 5 8 131
        85 years and over
    		 0 0 0 0 0 0 0
    Sex: Female, Male
    Units: Participants
        Female
    		 134 135 132 22 18 25 466
        Male
    		 22 23 24 4 8 2 83
    Race/Ethnicity, Customized
    Units: Subjects
        AMERICAN INDIAN OR ALASKA NATIVE
    		 1 0 0 0 0 0 1
        ASIAN
    		 13 15 12 3 2 2 47
        BLACK OR AFRICAN AMERICAN
    		 5 8 6 2 0 2 23
        MISSING
    		 0 2 0 0 0 0 2
        MULTIPLE
    		 0 0 0 1 0 0 1
        WHITE
    		 137 133 138 20 24 23 475
    Age, Continuous
    Units: YEARS
        arithmetic mean (standard deviation)
    		 56.7 ± 10.59 56.0 ± 10.52 57.5 ± 10.69 51.6 ± 11.19 57.3 ± 8.99 57.6 ± 10.89 -
    Subject analysis sets

    Subject analysis set title
    Pooled Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Placebo + csDMARD administered by weekly subcutaneous injection until Week 12. The placebo arms are pooled into a single placebo arm.

    Subject analysis sets values
    		 Pooled Placebo
    Number of subjects
    79
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units:
        
    ±
    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
    Age, Continuous
    Units: YEARS
        arithmetic mean (standard deviation)
    37.7 ± 5.74

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    GSK3196165 90mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received GSK3196165 90 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    GSK3196165 150mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received GSK3196165 150 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    Sarilumab 200mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Sarilumab 200 mg + csDMARD administered by subcutaneous injection of sarilumab every other week plus with placebo injection in the intervening weeks to maintain the blind.

    Reporting group title
    Placebo + csDMARD and GSK3196165 90mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to(<=)84 years received Placebo +csDMARD until Week 12 later switched toGSK3196165 90 mg +csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    Placebo + csDMARD and GSK3196165 150mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Placebo + csDMARD until Week 12 later switched to GSK3196165 150 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Placebo + csDMARD until Week 12 later switched to Sarilumab 200mg + csDMARD administered by subcutaneous injection of sarilumab every other week plus with placebo injection in the intervening weeks to maintain the blind.

    Subject analysis set title
    Pooled Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Placebo + csDMARD administered by weekly subcutaneous injection until Week 12. The placebo arms are pooled into a single placebo arm.

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

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    End point title
    		 Percentage of participants with 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12 superiority comparison with placebo [1]
    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 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 a reference for the comparison of active treatment arms.
    End point type
    Primary
    End point timeframe
    Week 12
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    44.8
    50.7
    57.5
    37.7
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The null hypothesis is that there is no difference between 90 mg dose of GSK3196165 and placebo in the proportion of participants achieving ACR20 response at Week 12 versus the alternative hypothesis that the 90 mg dose of GSK3196165 differs from placebo in the proportion of participants with ACR20 response at Week 12
    Comparison groups
    GSK3196165 90mg + csDMARD v Pooled Placebo
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2868
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.38
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 2.48
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    The null hypothesis is that there is no difference between 150 mg dose of GSK3196165 and placebo in the percentage of participants achieving ACR20 response at Week 12 versus the alternative hypothesis that the 150 mg dose of GSK3196165 differs from placebo in the percentage of participants with ACR20 response at Week 12
    Comparison groups
    GSK3196165 150mg + csDMARD v Pooled Placebo
    Number of subjects included in analysis
    237
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0596
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.75
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 3.15
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    The null hypothesis is that there is no difference between 150 mg dose of GSK3196165 and 200 mg dose of sarilumab alternating with placebo every week in the proportion of participants achieving ACR20 response at Week 12 versus the alternative hypothesis that the 150 mg dose of GSK3196165 differs from 200 mg dose of sarilumab alternating with placebo every week in the proportion of participants with ACR20 response at Week 12
    Comparison groups
    GSK3196165 150mg + csDMARD v Sarilumab 200mg + csDMARD
    Number of subjects included in analysis
    314
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2308
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.75
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 1.2
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    The null hypothesis is that there is no difference between 90 mg dose of GSK3196165 and 200 mg dose of sarilumab alternating with placebo every week in the proportion of participants achieving ACR20 response at Week 12 versus the alternative hypothesis that the 90 mg dose of GSK3196165 differs from 200 mg dose of sarilumab alternating with placebo every week in the proportion of participants with ACR20 response at Week 12
    Comparison groups
    GSK3196165 90mg + csDMARD v Sarilumab 200mg + csDMARD
    Number of subjects included in analysis
    312
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0293
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.59
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.36
         upper limit
    		 0.95
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    The null hypothesis is that there is no difference between 200 mg dose of Sarilumab alternating with placebo every week and placebo in the proportion of participants achieving ACR20 response at Week 12 versus the alternative hypothesis that the 200 mg dose of Sarilumab alternating with placebo every week differs from placebo in the proportion of participants with ACR20 response at Week 12
    Comparison groups
    Sarilumab 200mg + csDMARD v Pooled Placebo
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0049
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.34
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 1.29
         upper limit
    		 4.23

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

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    End point title
    		 Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) (versus Placebo) at Week 12 [2]
    End point description
    Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the difficulty of a participant in eight domains of daily living activities: Dressing & grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Common daily activities. Overall HAQ-DI score was computed as the 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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) 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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Scores on a scale
        least squares mean (standard error)
    -0.33 ± 0.044
    -0.41 ± 0.043
    -0.46 ± 0.044
    -0.23 ± 0.061
    No statistical analyses for this end point

    Secondary: Percentage of participants with Clinical disease activity index (CDAI) total score <=10 (CDAI Low disease activity [LDA]) at Week 12

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    End point title
    		 Percentage of participants with Clinical disease activity index (CDAI) total score <=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 (TJC28), 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). 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.
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    20.7
    18.2
    28.1
    14.2
    No statistical analyses for this end point

    Secondary: Percentage of participants with CDAI total score <=10 (CDAI LDA) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with CDAI total score <=10 (CDAI LDA) at Week 24 for treatment arms that started study intervention from Day 1 [4]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. LDA is achieved when CDAI total score <=10.
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    31.2
    30.1
    42.6
    No statistical analyses for this end point

    Secondary: Percentage of participants with CDAI total score <=10 (CDAI LDA) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with CDAI total score <=10 (CDAI LDA) at Week 24 for placebo switched arms that started study intervention from Week 12 [5]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. LDA is achieved when CDAI total score <=10.
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    24.0
    42.0
    36.1
    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 [6]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. A negative CDAI total score change from baseline indicates an improvement in disease activity. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Scores on a scale
        least squares mean (standard error)
    -16.87 ± 1.03
    -17.23 ± 1.018
    -20.22 ± 1.027
    -14.86 ± 1.438
    No statistical analyses for this end point

    Secondary: Change from Baseline in CDAI total score at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in CDAI total score at Week 24 for treatment arms that started study intervention from Day 1 [7]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28), 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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Scores on a scale
        least squares mean (standard error)
    -20.93 ± 1.04
    -20.75 ± 1.022
    -23.22 ± 1.048
    No statistical analyses for this end point

    Secondary: Change from Baseline in Arthritis pain Visual Analogue Scale (VAS) at Week 12

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    End point title
    		 Change from Baseline in Arthritis pain Visual Analogue Scale (VAS) at Week 12 [8]
    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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Score on scale
        least squares mean (standard error)
    -19.35 ± 2.127
    -21.17 ± 2.088
    -25.93 ± 2.12
    -16.73 ± 2.939
    No statistical analyses for this end point

    Secondary: Change from Baseline in CDAI total score at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in CDAI total score at Week 24 for placebo switched arms that started study intervention from Week 12 [9]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28), 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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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 + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Scores on a scale
        least squares mean (standard error)
    -16.84 ± 2.476
    -22.91 ± 2.439
    -20.38 ± 2.380
    No statistical analyses for this end point

    Secondary: Change from Baseline in Arthritis pain VAS at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in Arthritis pain VAS at Week 24 for treatment arms that started study intervention from Day 1 [10]
    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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Scores on a scale
        least squares mean (standard error)
    -25.06 ± 2.153
    -24.31 ± 2.115
    -30.62 ± 2.141
    No statistical analyses for this end point

    Secondary: Change from Baseline in Arthritis pain VAS at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in Arthritis pain VAS at Week 24 for placebo switched arms that started study intervention from Week 12 [11]
    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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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 + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Scores on a scale
        least squares mean (standard error)
    -16.98 ± 5.169
    -32.74 ± 5.029
    -18.60 ± 4.964
    No statistical analyses for this end point

    Secondary: Percentage of participants with CDAI total score <=2.8 (CDAI Remission) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with CDAI total score <=2.8 (CDAI Remission) at Week 24 for placebo switched arms that started study intervention from 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 (TJC28), 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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity.
    End point type
    Secondary
    End point timeframe
    Week 24
    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
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    5.1
    13.2
    8.4
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants with CDAI total score <=2.8 (CDAI Remission) at Week 24 for treatment arms that 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 (TJC28), 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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity.
    End point type
    Secondary
    End point timeframe
    Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    7.9
    8.4
    8.3
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants with CDAI total score <=2.8 (CDAI Remission) at Week 12 [14]
    End point description
    Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (TJC28),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). CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. 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.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    2.2
    4.3
    8.7
    0.6
    No statistical analyses for this end point

    Secondary: Percentage of participants with ACR20 at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with ACR20 at Week 24 for treatment arms that started study intervention from Day 1 [15]
    End point description
    ACR20 is calculated as a 20% improvement from Baseline in TJC68 and SJC66 and a 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) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    58.1
    60.5
    65.1
    No statistical analyses for this end point

    Secondary: Percentage of participants with ACR20 at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with ACR20 at Week 24 for placebo switched arms that started study intervention from Week 12 [16]
    End point description
    ACR20 is calculated as a 20% improvement from Baseline in TJC68 and SJC66 and a 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) (VAS values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    61.2
    70.7
    55.8
    No statistical analyses for this end point

    Secondary: Percentage of participants with ACR50 at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with ACR50 at Week 24 for treatment arms that started study intervention from Day 1 [17]
    End point description
    ACR50 is calculated as a 50% improvement from Baseline in TJC68 and SJC66 and a 50% 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 values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    23.6
    30.1
    42.9
    No statistical analyses for this end point

    Secondary: Percentage of participants with 50% improvement in American College of Rheumatology criteria (ACR50) at Week 12

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    End point title
    		 Percentage of participants with 50% improvement in American College of Rheumatology criteria (ACR50) at Week 12 [18]
    End point description
    ACR50 is calculated as a 50% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 50% 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)). 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.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    18.2
    22.5
    25.9
    11.5
    No statistical analyses for this end point

    Secondary: Percentage of participants with ACR50 at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with ACR50 at Week 24 for placebo switched arms that started study intervention from Week 12 [19]
    End point description
    ACR50 is calculated as a 50% improvement from Baseline in TJC68 and SJC66 and a 50% 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 values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).
    End point type
    Secondary
    End point timeframe
    Week 24
    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 + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    13.1
    41.8
    24.0
    No statistical analyses for this end point

    Secondary: Percentage of participants with 70% improvement in American College of Rheumatology criteria (ACR70) at Week 12

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    End point title
    		 Percentage of participants with 70% improvement in American College of Rheumatology criteria (ACR70) at Week 12 [20]
    End point description
    ACR70 is calculated as a 70% improvement from Baseline in Tender Joint Count 68 (TJC68) and Swollen Joint Count 66 (SJC66) and a 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)). 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.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    5.9
    10.8
    13.3
    6.1
    No statistical analyses for this end point

    Secondary: Percentage of participants with ACR70 at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with ACR70 at Week 24 for placebo switched arms that started study intervention from Week 12 [21]
    End point description
    ACR70 is calculated as a 70% improvement from Baseline in TJC68 and SJC66 and a 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 values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    4.9
    21.4
    12.1
    No statistical analyses for this end point

    Secondary: Percentage of participants with ACR70 at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with ACR70 at Week 24 for treatment arms that started study intervention from Day 1 [22]
    End point description
    ACR70 is calculated as a 70% improvement from Baseline in TJC68 and SJC66 and a 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 values from 0=best to 100=worst), Patient Assessment of Arthritis Pain (VAS values from 0=no pain to 100=most severe pain), Health Assessment Questionnaire-Disability Index (HAQ-DI) (0=least difficulty to 3=extreme difficulty) and an acute-phase reactant (high sensitivity C-reactive Protein mg/L (hsCRP).
    End point type
    Secondary
    End point timeframe
    Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    12.3
    13.2
    22.7
    No statistical analyses for this end point

    Secondary: Percentage of participants with DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for treatment arms that started study intervention from Day 1 [23]
    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 indicates less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=3.2 . A negative change from baseline in DAS28-CRP indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    26.8
    24.8
    46.9
    No statistical analyses for this end point

    Secondary: Percentage of participants with 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 with Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP) <=3.2 (DAS28-CRP LDA) at Week 12 [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 indicates less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=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.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    17
    17
    40.1
    13.2
    No statistical analyses for this end point

    Secondary: Percentage of participants with DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with DAS28-CRP <=3.2 (DAS28-CRP LDA) at Week 24 for placebo switched arms that started study intervention from Week 12 [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 indicates less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP<=3.2 . A negative change from baseline in DAS28-CRP indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Week 24
    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 + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    12.5
    43.1
    55.9
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants with DAS28 Erythrocyte Sedimentation Rate (ESR) <=3.2 (DAS28-ESR LDA) at Week 12 [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. 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.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    13.3
    8.5
    36.2
    1.9
    No statistical analyses for this end point

    Secondary: Percentage of participants with DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for treatment arms that started study intervention from Day 1 [27]
    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. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    17.4
    17.2
    45.8
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants with DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 12 [28]
    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 indicates less disease activity. Remission is achieved when DAS28-CRP <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.
    End point type
    Secondary
    End point timeframe
    Week 12
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    10.2
    7.2
    22.2
    1.8
    No statistical analyses for this end point

    Secondary: Percentage of participants with DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with DAS28-ESR <=3.2 (DAS28-ESR LDA) at Week 24 for placebo switched arms that started study intervention from Week 12 [29]
    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. Low disease activity (LDA) is achieved when DAS28-ESR<=3.2. A negative change from baseline in DAS28-ESR indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Week 24
    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 + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    5.7
    33.4
    40.0
    No statistical analyses for this end point

    Secondary: Percentage of participants with DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for placebo switched arms that started study intervention from Week 12 [30]
    End point description
    The DAS28-CRP arthritis 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 indicates less disease activity. Remission is achieved when DAS28-CRP <2.6. A negative change from baseline in DAS28-CRP indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Week 24
    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
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    6.8
    26.6
    32.0
    No statistical analyses for this end point

    Secondary: Percentage of participants with DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with DAS28-CRP <2.6 (DAS28-CRP Remission) at Week 24 for treatment arms that started study intervention from Day 1 [31]
    End point description
    The DAS28-CRP arthritis 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 indicates less disease activity. Remission is achieved when DAS28-CRP <2.6. A negative change from baseline in DAS28-CRP indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    16.2
    13.9
    32.6
    No statistical analyses for this end point

    Secondary: Percentage of participants with DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for treatment arms that started study intervention from Day 1 [32]
    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 indicates less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    10.8
    8.9
    29.8
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants with DAS28-ESR <2.6 (DAS28-ESR Remission) at Week 12 [33]
    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 indicates 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.
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    3.1
    5.7
    23
    0.7
    No statistical analyses for this end point

    Secondary: Percentage of participants with DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with DAS28-ESR <2.6 (DAS28-ESR Remission) Week 24 for placebo switched arms that started study intervention from Week 12 [34]
    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 indicates less disease activity. Remission is achieved when DAS28-ESR <2.6. A negative change from baseline in DAS28-ESR indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    1.1
    10.0
    24.2
    No statistical analyses for this end point

    Secondary: Percentage of participants with a good/moderate EULAR response at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with a good/moderate EULAR response at Week 24 for treatment arms that started study intervention from Day 1 [35]
    End point description
    DAS28-CRP and DAS28-ESR scores categorised using EULAR response criteria. Response based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to baseline (Good response = DAS28 change >1.2 with current DAS28 ≤3.2; Moderate response = DAS28 change >0.6 with current DAS28 >3.2-5.1; Non-response = DAS28 change ≤0.6 and current DAS28 >5.1).
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
        number (not applicable)
    76.3
    71.3
    86.6
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of participants with a good/moderate European League against Rheumatism (EULAR) response at Week 12 [36]
    End point description
    DAS28-CRP and DAS28-ESR scores categorized using EULAR response criteria. Response based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to baseline (Good response = DAS28 change >1.2 with current DAS28 ≤3.2; Moderate response = DAS28 change >0.6 with current DAS28 >3.2-5.1; Non-response = DAS28 change ≤0.6 and current DAS28 >5.1). 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.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
        number (not applicable)
    66.3
    68.4
    84.1
    62.9
    No statistical analyses for this end point

    Secondary: Percentage of participants with a good/moderate EULAR response at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with a good/moderate EULAR response at Week 24 for placebo switched arms that started study intervention from Week 12 [37]
    End point description
    DAS28-CRP and DAS28-ESR scores categorised using EULAR response criteria. Response based on the combination of current DAS28 score and the improvement in the current DAS28 score relative to baseline (Good response = DAS28 change >1.2 with current DAS28 ≤3.2; Moderate response = DAS28 change >0.6 with current DAS28 >3.2-5.1; Non-response = DAS28 change ≤0.6 and current DAS28 >5.1).
    End point type
    Secondary
    End point timeframe
    Week 24
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
        number (not applicable)
    73.3
    76.7
    83.7
    No statistical analyses for this end point

    Secondary: Percentage of participants with ACR/EULAR remission at Week 12

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    End point title
    		 Percentage of participants with ACR/EULAR remission at Week 12 [38]
    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.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Percentage of participants
    2
    4
    9
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants with ACR/EULAR remission at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Percentage of participants with ACR/EULAR remission at Week 24 for placebo switched arms that started study intervention from Week 12 [39]
    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 (CRP) ≤ 1mg/dl and patient's global assessment of disease activity (PtGA) ≤ 10.
    End point type
    Secondary
    End point timeframe
    Week 24
    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
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Percentage of participants
    1
    1
    1
    No statistical analyses for this end point

    Secondary: Percentage of participants with ACR/EULAR remission at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Percentage of participants with ACR/EULAR remission at Week 24 for treatment arms that started study intervention from Day 1 [40]
    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 (CRP) ≤ 1mg/dl and patient's global assessment of disease activity (PtGA) ≤ 10.
    End point type
    Secondary
    End point timeframe
    Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Percentage of participants
    6
    4
    5
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in DAS28-CRP and DAS28-ESR at Week 12 [41]
    End point description
    DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR in mm/hr (mm/hour) and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Scores on a scale
    least squares mean (standard error)
        DAS28-CRP
    -1.34 ± 0.1
    -1.42 ± 0.098
    -2.15 ± 0.1
    -1.08 ± 0.139
        DAS28-ESR
    -1.41 ± 0.109
    -1.46 ± 0.106
    -2.57 ± 0.108
    -1.06 ± 0.152
    No statistical analyses for this end point

    Secondary: Change from Baseline in DAS28-CRP and DAS28-ESR at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in DAS28-CRP and DAS28-ESR at Week 24 for treatment arms that started study intervention from Day 1 [42]
    End point description
    DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR in mm/hr (mm/hour) and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Scores on a scale
    least squares mean (standard error)
        DAS28-CRP
    -1.67 ± 0.108
    -1.67 ± 0.106
    -2.38 ± 0.109
        DAS28-ESR
    -1.7 ± 0.121
    -1.68 ± 0.117
    -2.85 ± 0.121
    No statistical analyses for this end point

    Secondary: Change from Baseline in DAS28-CRP and DAS28-ESR at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in DAS28-CRP and DAS28-ESR at Week 24 for placebo switched arms that started study intervention from Week 12 [43]
    End point description
    DAS28-CRP and DAS28-ESR are measure of RA disease activity calculated using Swollen Joint Count 28 (TJC28), Tender Joint Count 28 (TJC28), high sensitivity C-reactive Protein (hsCRP in mg/L)/Erythrocyte sedimentation rate (ESR in mm/hr (mm/hour) and patient's global assessment of disease activity (PtGA) transformed to a 0-10 scale. Total score approximate range 0-9.4, with higher scores indicating more disease activity.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Scores on a scale
    least squares mean (standard error)
        DAS28-CRP
    -1.25 ± 0.264
    -2.08 ± 0.258
    -2.15 ± 0.248
        DAS28-ESR
    -1.28 ± 0.282
    -1.94 ± 0.294
    -2.47 ± 0.266
    No statistical analyses for this end point

    Secondary: Change from Baseline in HAQ-DI at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in HAQ-DI at Week 24 for placebo switched arms that started study intervention from Week 12 [44]
    End point description
    Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the difficulty of a participant in eight domains of daily activities: Dressing & grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Common daily activities. 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=least difficulty to 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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 + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Scores on a scale
        least squares mean (standard error)
    -0.27 ± 0.121
    -0.62 ± 0.119
    -0.32 ± 0.116
    No statistical analyses for this end point

    Secondary: Change from Baseline in HAQ-DI at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in HAQ-DI at Week 24 for treatment arms that started study intervention from Day 1 [45]
    End point description
    Health Assessment Questionnaire-Disability Index (HAQ-DI) is a 20-question instrument that assesses the difficulty of a participant in eight domains of daily activities: Dressing & grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, Common daily activities. 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=least difficulty to 3=extreme difficulty. Higher overall score indicates greater disability. A negative change from baseline indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Scores on a scale
        least squares mean (standard error)
    -0.39 ± 0.05
    -0.45 ± 0.049
    -0.48 ± 0.05
    No statistical analyses for this end point

    Secondary: Change from Baseline in FACIT-Fatigue at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in FACIT-Fatigue at Week 24 for treatment arms that started study intervention from Day 1 [46]
    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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [46] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Scores on a scale
        least squares mean (standard error)
    6.55 ± 0.795
    7.21 ± 0.777
    7.99 ± 0.806
    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 [47]
    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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) 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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Scores on a scale
        least squares mean (standard error)
    5.5 ± 0.735
    6.8 ± 0.724
    7.3 ± 0.749
    5.45 ± 1.023
    No statistical analyses for this end point

    Secondary: Change from Baseline in FACIT-Fatigue at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in FACIT-Fatigue at Week 24 for placebo switched arms that started study intervention from Week 12 [48]
    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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Scores on a scale
        least squares mean (standard error)
    5.48 ± 1.927
    8.56 ± 1.852
    7.21 ± 1.824
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 PCS at Week 24 for treatment arms that started study intervention from Day 1 [49]
    End point description
    The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The PCS is an aggregated score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. T-score scale was used for PCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall physical health. Quality Metrics software was used for scoring for SF-36.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Scores on a scale
        least squares mean (standard error)
    5.67 ± 0.707
    5.5 ± 0.694
    7.18 ± 0.71
    No statistical analyses for this end point

    Secondary: Change from Baseline in Subject-completed Medical Outcomes Study Short-Form 36 (SF-36) Physical Component Scores (PCS) at Week 12

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    End point title
    		 Change from Baseline in Subject-completed Medical Outcomes Study Short-Form 36 (SF-36) Physical Component Scores (PCS) at Week 12 [50]
    End point description
    The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The PCS is an aggregated score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. T-score scale was used for PCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall physical health. Quality Metrics software was used for scoring for SF-36. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) 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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Scores on a scale
        least squares mean (standard error)
    5.08 ± 0.619
    5.03 ± 0.61
    5.61 ± 0.627
    3.72 ± 0.866
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 PCS at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in SF-36 PCS at Week 24 for placebo switched arms that started study intervention from Week 12 [51]
    End point description
    The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The PCS is an aggregated score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. T-score scale was used for PCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall physical health. Quality Metrics software was used for scoring for SF-36.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Scores on a scale
        least squares mean (standard error)
    3.76 ± 1.687
    8.63 ± 1.672
    4.16 ± 1.611
    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 [52]
    End point description
    The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Scores on a scale
        least squares mean (standard error)
    1.64 ± 0.731
    3.45 ± 0.72
    4.15 ± 0.744
    1.61 ± 1.024
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in SF-36 MCS at Week 24 for treatment arms that started study intervention from Day 1 [53]
    End point description
    The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Scores on a scale
        least squares mean (standard error)
    2.22 ± 0.772
    3.05 ± 0.756
    3.61 ± 0.78
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 MCS at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in SF-36 MCS at Week 24 for placebo switched arms that started study intervention from Week 12 [54]
    End point description
    The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The score for a domain was an average of the individual question scores, which were scaled 0-100; higher score represents better health. The MCS is an aggregated score derived from 4 domains (social functioning, vitality, mental health, and role-emotional domains) representing overall mental health. T-score scale was used for MCS with mean of 50 and SD of 10; higher score represents better health. A positive change from baseline indicates an improvement in overall mental health. Quality Metrics software was used for scoring for SF-36.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    26
    26
    27
    Units: Scores on a scale
        least squares mean (standard error)
    1.44 ± 1.891
    1.10 ± 1.855
    2.76 ± 1.800
    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 [55]
    End point description
    The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are scaled between 0 to 100, where higher score represents better health. A positive change from baseline 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    143
    148
    138
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Bodily Pain - PCS
    17 ± 21.45
    16.8 ± 22.2
    19.8 ± 23.27
        General Health - PCS
    6.3 ± 15.89
    6.7 ± 16.07
    6.7 ± 15.69
        Role Physical - PCS
    12.94 ± 22.371
    14.19 ± 25.155
    13.81 ± 23.488
        Physical Function - PCS
    9.69 ± 21.423
    14.22 ± 23.909
    13.15 ± 24.135
        Mental Health - MCS
    4.3 ± 19.3
    7.6 ± 16.9
    8.2 ± 18.55
        Role Emotional - MCS
    5.77 ± 22.405
    9.4 ± 25.128
    10.93 ± 23.908
        Social Function - MCS
    6.99 ± 23.107
    10.73 ± 27.51
    11.59 ± 24.383
        Vitality - MCS
    9.48 ± 18.03
    11.82 ± 19.94
    13 ± 19.895
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 domain scores at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in SF-36 domain scores at Week 24 for treatment arms that started study intervention from Day 1 [56]
    End point description
    The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are scaled between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    140
    147
    136
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Bodily Pain - PCS
    20.7 ± 22.82
    18.5 ± 22.43
    23.9 ± 27.29
        General Health - PCS
    6.4 ± 15.25
    6.7 ± 16.3
    8.8 ± 17.3
        Role Physical - PCS
    13.97 ± 21.332
    15.22 ± 27.352
    17.37 ± 26.25
        Physical Function - PCS
    11.43 ± 23.714
    16.36 ± 25.64
    18.86 ± 24.472
        Mental Health - MCS
    6.1 ± 17.16
    8.4 ± 19.63
    10 ± 18.71
        Role Emotional - MCS
    5.83 ± 23.522
    7.99 ± 28.03
    8.88 ± 26.589
        Social Function - MCS
    9.46 ± 25.704
    10.37 ± 29.237
    12.04 ± 24.599
        Vitality - MCS
    11.29 ± 17.913
    13.22 ± 21.245
    16.31 ± 19.854
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 domain scores at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in SF-36 domain scores at Week 24 for placebo switched arms that started study intervention from Week 12 [57]
    End point description
    The Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are scaled between 0 to 100, where higher score represents better health. A positive change from baseline indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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 + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    23
    24
    25
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Bodily Pain - PCS
    15.7 ± 21.91
    20.4 ± 26.91
    16.9 ± 23.99
        General Health - PCS
    5.6 ± 14.98
    3.4 ± 17.47
    4.4 ± 17.20
        Role Physical - PCS
    10.33 ± 21.204
    17.19 ± 19.352
    12.25 ± 20.530
        Physical Function - PCS
    7.39 ± 19.121
    18.75 ± 23.417
    6.20 ± 20.630
        Mental Health - MCS
    5.9 ± 14.11
    5.2 ± 23.29
    5.4 ± 18.54
        Role Emotional - MCS
    7.97 ± 21.242
    4.17 ± 28.019
    6.67 ± 28.667
        Social Function - MCS
    13.04 ± 23.681
    6.25 ± 37.771
    5.50 ± 36.279
        Vitality - MCS
    8.42 ± 13.926
    10.16 ± 27.263
    11.75 ± 20.832
    No statistical analyses for this end point

    Secondary: Incidence of Adverse events (AEs), Serious adverse event (SAEs), Adverse events of special interest (AESI)

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    End point title
    		 Incidence of Adverse events (AEs), Serious adverse event (SAEs), Adverse events of special interest (AESI) [58]
    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.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: Participants
        AE
    92
    99
    98
    37
        SAE
    8
    1
    12
    2
        AESI
    16
    15
    33
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline in neutrophil, lymphocyte, platelet count (Giga cells per liter) at Week 12

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    End point title
    		 Change from Baseline in neutrophil, lymphocyte, platelet count (Giga cells per liter) at Week 12 [59]
    End point description
    Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    141
    143
    138
    Units: 10^9/L (Giga cells per liter)
    arithmetic mean (standard deviation)
        Lymphocytes
    -0.039 ± 0.5089
    -0.01 ± 0.508
    -0.057 ± 0.4989
        Neutrophils
    -0.255 ± 1.5469
    -0.412 ± 2.0477
    -1.843 ± 2.1359
        Platelets
    -10.9 ± 56.51
    -17.3 ± 60.17
    -76.5 ± 62.76
    No statistical analyses for this end point

    Secondary: Change from Baseline in neutrophil, lymphocyte, platelet count (Giga cells per liter) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in neutrophil, lymphocyte, platelet count (Giga cells per liter) at Week 24 for treatment arms that started study intervention from Day 1 [60]
    End point description
    Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    138
    141
    127
    Units: 10^9/L (Giga cells per liter)
    arithmetic mean (standard deviation)
        Lymphocytes
    -0.079 ± 0.5135
    0.012 ± 0.5939
    -0.108 ± 0.52
        Neutrophils
    -0.388 ± 1.692
    -0.422 ± 1.7963
    -1.99 ± 2.3395
        Platelets
    -9.3 ± 50.96
    -9 ± 64.92
    -79.2 ± 71.13
    No statistical analyses for this end point

    Secondary: Change from Baseline in neutrophil, lymphocyte, platelet count (Giga cells per liter) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in neutrophil, lymphocyte, platelet count (Giga cells per liter) at Week 24 for placebo switched arms that started study intervention from Week 12 [61]
    End point description
    Blood samples was collected for the assessment of change from baseline in hematology parameters including neutrophil, lymphocyte, platelet count.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    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
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    21
    24
    26
    Units: 10^9/L (Giga cells per liter)
    arithmetic mean (standard deviation)
        Lymphocytes
    -0.030 ± 0.4192
    0.083 ± 0.3298
    -0.094 ± 0.4478
        Neutrophils
    -0.611 ± 1.7602
    -0.643 ± 1.3489
    -2.016 ± 2.1132
        Platelets
    -43.6 ± 53.10
    -12.7 ± 74.80
    -70.8 ± 82.58
    No statistical analyses for this end point

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

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    End point title
    		 Change from Baseline in white blood cell (WBC) count (Giga cells per liter) at Week 12 [62]
    End point description
    Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: 10^9/L (Giga cells per liter)
        arithmetic mean (standard deviation)
    -0.29 ± 1.753
    -0.42 ± 2.072
    -1.95 ± 2.325
    -0.09 ± 1.558
    No statistical analyses for this end point

    Secondary: Change from Baseline in WBC count (Giga cells per liter) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in WBC count (Giga cells per liter) at Week 24 for treatment arms that started study intervention from Day 1 [63]
    End point description
    Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: 10^9/L (Giga cells per liter)
        arithmetic mean (standard deviation)
    -0.45 ± 1.851
    -0.43 ± 1.787
    -2.15 ± 2.51
    No statistical analyses for this end point

    Secondary: Change from Baseline in WBC count (Giga cells per liter) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in WBC count (Giga cells per liter) at Week 24 for placebo switched arms that started study intervention from Week 12 [64]
    End point description
    Blood samples was collected for the assessment of change from baseline in hematology parameter WBC count.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    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
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    21
    24
    26
    Units: 10^9/L (Giga cells per liter)
        arithmetic mean (standard deviation)
    -0.66 ± 1.824
    -0.60 ± 1.452
    -2.05 ± 2.271
    No statistical analyses for this end point

    Secondary: Change from Baseline in hemoglobin level (Grams per liter) Week 12

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    End point title
    		 Change from Baseline in hemoglobin level (Grams per liter) Week 12 [65]
    End point description
    Blood samples was collected for the assessment of change from baseline in hematology parameter hemoglobin level. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: g/L (Grams per liter)
        arithmetic mean (standard deviation)
    -0.9 ± 8.06
    0.3 ± 8.54
    5.5 ± 9.19
    -2 ± 7.98
    No statistical analyses for this end point

    Secondary: Change from Baseline in hemoglobin level (Grams per liter) Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in hemoglobin level (Grams per liter) Week 24 for placebo switched arms that started study intervention from Week 12 [66]
    End point description
    Blood samples was collected for the assessment of change from baseline in in hematology parameter hemoglobin level.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    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
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    21
    24
    26
    Units: g/L (Grams per liter)
        arithmetic mean (standard deviation)
    3.5 ± 7.44
    0.2 ± 10.85
    7.0 ± 11.51
    No statistical analyses for this end point

    Secondary: Change from Baseline in hemoglobin level (Grams per liter) Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in hemoglobin level (Grams per liter) Week 24 for treatment arms that started study intervention from Day 1 [67]
    End point description
    Blood samples was collected for the assessment of change from baseline in in hematology parameter hemoglobin level.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: g/L (Grams per liter)
        arithmetic mean (standard deviation)
    -1.9 ± 9.05
    -1 ± 8.63
    5.8 ± 11.07
    No statistical analyses for this end point

    Secondary: Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) gamma-glutamyl transferase(GGT) levels (International units per liter) at Week 12

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    End point title
    		 Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) gamma-glutamyl transferase(GGT) levels (International units per liter) at Week 12 [68]
    End point description
    Blood samples was collected for the assessment of change from baseline in laboratory parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP) gamma-glutamyl transferase (GGT) levels. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    146
    146
    139
    Units: IU/L (International units per liter)
    arithmetic mean (standard deviation)
        AST
    0.6 ± 10.29
    0.7 ± 8.52
    4.5 ± 11.43
        ALT
    0.8 ± 16.22
    -0.7 ± 12.95
    8.1 ± 21.3
        AP
    0.7 ± 14.42
    -3 ± 14.94
    -15.6 ± 20.63
        GGT
    -0.8 ± 14.24
    -2.6 ± 15.23
    0.6 ± 12.37
    No statistical analyses for this end point

    Secondary: Change from Baseline in AST, ALT, AP, GGT levels (International units per liter) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in AST, ALT, AP, GGT levels (International units per liter) at Week 24 for treatment arms that started study intervention from Day 1 [69]
    End point description
    Blood samples was collected for the assessment of change from baseline in laboratory parameters including AST, ALT, AP, GGT levels.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    141
    145
    129
    Units: IU/L (International units per liter)
    arithmetic mean (standard deviation)
        AST
    1.7 ± 7.89
    2.1 ± 11.21
    3.0 ± 9.29
        ALT
    1.6 ± 12.73
    1.9 ± 20.52
    6.2 ± 12.98
        AP
    1.8 ± 16.48
    -1.7 ± 18.76
    -14.3 ± 19.23
        GGT
    -0.3 ± 13.07
    -0.3 ± 25.67
    0.9 ± 15.73
    No statistical analyses for this end point

    Secondary: Change from Baseline in AST, ALT, AP, GGT levels (International units per liter) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in AST, ALT, AP, GGT levels (International units per liter) at Week 24 for placebo switched arms that started study intervention from Week 12 [70]
    End point description
    Blood samples was collected for the assessment of change from baseline in laboratory parameters including AST, ALT, AP, GGT levels.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    21
    25
    26
    Units: IU/L (International units per liter)
    arithmetic mean (standard deviation)
        AST
    2.5 ± 6.12
    3.0 ± 9.46
    0.9 ± 17.04
        ALT
    3.3 ± 9.51
    4.2 ± 13.08
    3.5 ± 15.12
        AP
    2.0 ± 12.25
    1.4 ± 13.68
    -15.6 ± 18.77
        GGT
    4.4 ± 13.92
    -0.8 ± 7.11
    -1.4 ± 13.04
    No statistical analyses for this end point

    Secondary: Change from Baseline in albumin level (Grams per liter) at Week 12

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    End point title
    		 Change from Baseline in albumin level (Grams per liter) at Week 12 [71]
    End point description
    Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: g/L (Grams per liter)
        arithmetic mean (standard deviation)
    0 ± 2.5
    0.3 ± 2.38
    1.6 ± 2.64
    -0.4 ± 2.9
    No statistical analyses for this end point

    Secondary: Change from Baseline in albumin level (Grams per liter) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in albumin level (Grams per liter) at Week 24 for treatment arms that started study intervention from Day 1 [72]
    End point description
    Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: g/L (Grams per liter)
        arithmetic mean (standard deviation)
    0.2 ± 2.55
    0.2 ± 2.50
    2.0 ± 3.16
    No statistical analyses for this end point

    Secondary: Change from Baseline in albumin level (Grams per liter) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in albumin level (Grams per liter) at Week 24 for placebo switched arms that started study intervention from Week 12 [73]
    End point description
    Blood samples was collected for the assessment of change from baseline in laboratory parameter albumin level.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    21
    24
    26
    Units: g/L (Grams per liter)
        arithmetic mean (standard deviation)
    1.6 ± 3.75
    0.5 ± 2.43
    1.7 ± 2.76
    No statistical analyses for this end point

    Secondary: Change from Baseline in total bilirubin (Micromoles per liter) at Week 12

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    End point title
    		 Change from Baseline in total bilirubin (Micromoles per liter) at Week 12 [74]
    End point description
    Blood samples was collected for the assessment of change from baseline in laboratory parameter total bilirubin level. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Pooled Placebo
    Number of subjects analysed
    156
    158
    156
    79
    Units: umol/L (Micromoles per liter)
        arithmetic mean (standard deviation)
    0.1 ± 2.35
    0.4 ± 3.07
    2.3 ± 4.5
    0.3 ± 2.64
    No statistical analyses for this end point

    Secondary: Change from Baseline in total bilirubin (Micromoles per liter) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in total bilirubin (Micromoles per liter) at Week 24 for treatment arms that started study intervention from Day 1 [75]
    End point description
    Blood samples was collected for the assessment of change from baseline in laboratory parameter bilirubin level.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: umol/L (Micromoles per liter)
        arithmetic mean (standard deviation)
    0.1 ± 2.06
    0.2 ± 2.70
    2.5 ± 4.11
    No statistical analyses for this end point

    Secondary: Change from Baseline in total bilirubin (Micromoles per liter) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in total bilirubin (Micromoles per liter) at Week 24 for placebo switched arms that started study intervention from Week 12 [76]
    End point description
    Blood samples was collected for the assessment of change from baseline in laboratory parameter bilirubin level.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    21
    25
    26
    Units: umol/L (Micromoles per liter)
        arithmetic mean (standard deviation)
    0.8 ± 1.97
    -0.2 ± 3.17
    1.1 ± 3.39
    No statistical analyses for this end point

    Secondary: Change from Baseline in total cholesterol (Millimoles per liter) at Week 12

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    End point title
    		 Change from Baseline in total cholesterol (Millimoles per liter) at Week 12 [77]
    End point description
    Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    0 [78]
    0 [79]
    0 [80]
    Units: mmol/L (Millimoles per liter)
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    Notes
    [78] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [79] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [80] - 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 total cholesterol (Millimoles per liter) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in total cholesterol (Millimoles per liter) at Week 24 for treatment arms that started study intervention from Day 1 [81]
    End point description
    Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: mmol/L (Millimoles per liter)
        arithmetic mean (standard deviation)
    0.053 ± 1.0158
    0.061 ± 0.7881
    0.445 ± 0.8863
    No statistical analyses for this end point

    Secondary: Change from Baseline in total cholesterol (Millimoles per liter) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in total cholesterol (Millimoles per liter) at Week 24 for placebo switched arms that started study intervention from Week 12 [82]
    End point description
    Blood samples was collected for the assessment of change from baseline in lipid profile of total cholesterol levels.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [82] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    20
    23
    25
    Units: mmol/L (Millimoles per liter)
        arithmetic mean (standard deviation)
    0.126 ± 0.8456
    -0.006 ± 0.7593
    0.731 ± 0.8654
    No statistical analyses for this end point

    Secondary: Change from Baseline in fasting lipid profile: low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol (Millimoles per liter) at Week 12

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    End point title
    		 Change from Baseline in fasting lipid profile: low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol (Millimoles per liter) at Week 12 [83]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [83] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    0 [84]
    0 [85]
    0 [86]
    Units: mmol/L (Millimoles per liter)
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    Notes
    [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.
    [86] - 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 fasting lipid profile: LDL cholesterol, HDL cholesterol (Millimoles per liter) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in fasting lipid profile: LDL cholesterol, HDL cholesterol (Millimoles per liter) at Week 24 for placebo switched arms that started study intervention from Week 12 [87]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    20
    23
    25
    Units: mmol/L (Millimoles per liter)
    arithmetic mean (standard deviation)
        HDL Cholesterol, Direct
    0.049 ± 0.2578
    0.000 ± 0.2511
    0.107 ± 0.3202
        LDL Cholesterol
    0.041 ± 0.7034
    0.006 ± 0.6861
    0.513 ± 0.6822
    No statistical analyses for this end point

    Secondary: Change from Baseline in fasting lipid profile: LDL cholesterol, HDL cholesterol (Millimoles per liter) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in fasting lipid profile: LDL cholesterol, HDL cholesterol (Millimoles per liter) at Week 24 for treatment arms that started study intervention from Day 1 [88]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile including LDL cholesterol, HDL cholesterol levels.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    140
    142
    125
    Units: mmol/L (Millimoles per liter)
    arithmetic mean (standard deviation)
        HDL Cholesterol, Direct
    0.044 ± 0.2523
    0.051 ± 0.2931
    0.063 ± 0.2784
        LDL Cholesterol
    -0.026 ± 0.8577
    0.021 ± 0.6769
    0.334 ± 0.7472
    No statistical analyses for this end point

    Secondary: Change from Baseline in fasting lipid profile triglycerides (Millimoles per liter) at Week 12

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    End point title
    		 Change from Baseline in fasting lipid profile triglycerides (Millimoles per liter) at Week 12 [89]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels. 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.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 12
    Notes
    [89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    0 [90]
    0 [91]
    0 [92]
    Units: mmol/L (Millimoles per liter)
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    Notes
    [90] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [91] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    [92] - Data was not collected as there is no corresponding time point in schedule of activity of Protocol.
    No statistical analyses for this end point

    Secondary: Change from Baseline in fasting lipid profile triglycerides (Millimoles per liter) at Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline in fasting lipid profile triglycerides (Millimoles per liter) at Week 24 for treatment arms that started study intervention from Day 1 [93]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 01) and Week 24
    Notes
    [93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: mmol/L (Millimoles per liter)
        arithmetic mean (standard deviation)
    0.075 ± 0.5799
    -0.038 ± 0.5519
    0.103 ± 0.7552
    No statistical analyses for this end point

    Secondary: Change from Baseline in fasting lipid profile triglycerides (Millimoles per liter) at Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline in fasting lipid profile triglycerides (Millimoles per liter) at Week 24 for placebo switched arms that started study intervention from Week 12 [94]
    End point description
    Blood samples was collected for the assessment of change from baseline in fasting lipid profile triglycerides levels.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [94] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    20
    23
    25
    Units: mmol/L (Millimoles per liter)
        arithmetic mean (standard deviation)
    0.072 ± 0.4498
    -0.024 ± 0.5497
    0.243 ± 0.8130
    No statistical analyses for this end point

    Secondary: Number of participants with National Cancer Institute (NCI)-Common terminology criteria for adverse events (CTCAE) >=Grade 3 hematological/clinical chemistry abnormalities for treatment arms that started study intervention from Day 1

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    End point title
    		 Number of participants with National Cancer Institute (NCI)-Common terminology criteria for adverse events (CTCAE) >=Grade 3 hematological/clinical chemistry abnormalities for treatment arms that started study intervention from Day 1
    End point description
    Number of participants who reported NCI-CTCAE Grade 3 or higher for hematological and clinical chemistry abnormalities were summarized.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    155
    156
    153
    24
    25
    26
    Units: Participants
        Alanine aminotransferase increased, Total,Grade 3
    1
    2
    1
    0
    0
    0
        Alanine aminotransferase increased, Total,Grade 4
    0
    0
    0
    0
    0
    0
        Aspartate aminotransferase increased,Total,Grade 3
    1
    1
    0
    0
    0
    0
        Aspartate aminotransferase increased,Total,Grade 4
    0
    0
    0
    0
    0
    0
        Blood bilirubin increased, Total, Grade 3
    0
    0
    1
    0
    0
    0
        Blood bilirubin increased, Total, Grade 4
    0
    0
    0
    0
    0
    0
        Lymphocyte count decreased, Total, Grade 3
    6
    1
    2
    0
    0
    0
        Lymphocyte count decreased, Total, Grade 4
    0
    0
    1
    0
    0
    0
        Lymphocyte count increased, Total, Grade 3
    0
    0
    0
    0
    0
    0
        Lymphocyte count increased, Total, Grade 4
    0
    0
    0
    0
    0
    0
        Neutrophil count decreased, Total, Grade 3
    2
    1
    10
    1
    1
    2
        Neutrophil count decreased, Total, Grade 4
    1
    1
    4
    0
    0
    0
        Platelet count decreased, Total, Grade 3
    0
    0
    0
    0
    0
    0
        Platelet count decreased, Total, Grade 4
    0
    0
    0
    0
    0
    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 [95]
    End point description
    Blood samples were collected for markers which may influence rheumatoid arthritis. Concentrations of GM-CSF autoantibodies was determined.
    End point type
    Secondary
    End point timeframe
    At baseline
    Notes
    [95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: ug/L (microgram per liter)
        arithmetic mean (standard deviation)
    334.008 ± 823.7538
    417.378 ± 1632.7755
    250.015 ± 671.9296
    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 [96]
    End point description
    Blood samples were collected for anti-GSK3196165 antibodies detection assay using tiered testing schema: screening, confirmation and titration steps was used for immunogenicity analysis.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    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 + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    156
    158
    156
    Units: Participants
    4
    2
    0
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline 4-beta-hydroxy cholesterol, cholesterol at (Millimoles per liter) Week 12

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    End point title
    		 Change from Baseline 4-beta-hydroxy cholesterol, cholesterol at (Millimoles per liter) Week 12 [97]
    End point description
    Blood samples was collected for the assessment of change from baseline in lipid profile parameter including 4-beta-hydroxycholesterol, cholesterol levels. 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.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 12
    Notes
    [97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    139
    141
    134
    Units: mmol/L (Millimoles per liter)
    arithmetic mean (standard deviation)
        4-Beta-Hydroxycholesterol
    0.9897 ± 0.81483
    1.0156 ± 0.57323
    1.1148 ± 0.56873
        Cholesterol
    58.5438 ± 13.25606
    59.1757 ± 14.83734
    64.3791 ± 15.12089
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline 4-beta-hydroxy cholesterol, cholesterol at (Millimoles per liter) Week 24 for placebo switched arms that started study intervention from Week 12

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    End point title
    		 Change from Baseline 4-beta-hydroxy cholesterol, cholesterol at (Millimoles per liter) Week 24 for placebo switched arms that started study intervention from Week 12 [98]
    End point description
    Blood samples was collected for the assessment of change from baseline in lipid profile parameter including 4-beta-hydroxycholesterol, cholesterol levels.
    End point type
    Other pre-specified
    End point timeframe
    Baseline (Week 12) and Week 24
    Notes
    [98] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 Placebo + csDMARD and GSK3196165 90mg + csDMARD Placebo + csDMARD and GSK3196165 150mg + csDMARD Placebo + csDMARD and Sarilumab 200mg + csDMARD
    Number of subjects analysed
    20
    23
    24
    Units: mmol/L (Millimoles per liter)
    arithmetic mean (standard deviation)
        4-Beta-Hydroxycholesterol
    1.0180 ± 0.42435
    0.9467 ± 0.29136
    1.3897 ± 1.31589
        Cholesterol
    56.7570 ± 13.92076
    62.4284 ± 13.72140
    68.7768 ± 17.39453
    No statistical analyses for this end point

    Other pre-specified: Change from Baseline 4-beta-hydroxy cholesterol, cholesterol at (Millimoles per liter) Week 24 for treatment arms that started study intervention from Day 1

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    End point title
    		 Change from Baseline 4-beta-hydroxy cholesterol, cholesterol at (Millimoles per liter) Week 24 for treatment arms that started study intervention from Day 1 [99]
    End point description
    Blood samples was collected for the assessment of change from baseline in lipid profile parameter including 4-beta-hydroxycholesterol, cholesterol levels.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 24
    Notes
    [99] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoints are different for the different parts of the study.
    End point values
    		 GSK3196165 90mg + csDMARD GSK3196165 150mg + csDMARD Sarilumab 200mg + csDMARD
    Number of subjects analysed
    136
    139
    123
    Units: mmol/L (Millimoles per liter)
    arithmetic mean (standard deviation)
        4-Beta-Hydroxycholesterol
    0.9766 ± 0.45665
    1.0064 ± 0.58945
    1.1925 ± 0.57339
        Cholesterol
    59.1937 ± 14.12055
    58.9174 ± 15.00108
    65.2270 ± 14.70946
    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 arms collected during the timeframe Week 12 to Week 24. Experimental arms collected during from Week 0 to Week 24.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    GSK3196165 90mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received GSK3196165 90 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    Sarilumab 200mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Sarilumab 200 mg + csDMARD administered by subcutaneous injection of sarilumab every other week plus with placebo injection in the intervening weeks to maintain the blind.

    Reporting group title
    Placebo + csDMARD and Sarilumab 200 mg + csDMARD
    Reporting group description
    		 Participants received Placebo + csDMARD until Week 12 later switched to Sarilumab 200 mg + csDMARD administered by subcutaneous injection of sarilumab every other week plus with placebo injection in the intervening weeks to maintain the blind.

    Reporting group title
    Placebo + csDMARD and GSK3196165 90 mg + csDMARD
    Reporting group description
    		 Participants received Placebo + csDMARD until Week 12 later switched to GSK3196165 90 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    Placebo + csDMARD and GSK3196165 150 mg + csDMARD
    Reporting group description
    		 Participants received Placebo + csDMARD until Week 12 later switched to GSK3196165 150 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    GSK3196165 150mg + csDMARD
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received GSK3196165 150 mg + csDMARD administered by weekly subcutaneous injection.

    Reporting group title
    Pooled Placebo
    Reporting group description
    		 Participants between the ages of greater than or equal to (>=)18 years and less than or equal to (<=)84 years received Placebo + csDMARD administered by weekly subcutaneous injection until Week 12. The placebo arms are pooled into a single placebo arm.

    Serious adverse events
    		 GSK3196165 90mg + csDMARD Sarilumab 200mg + csDMARD Placebo + csDMARD and Sarilumab 200 mg + csDMARD Placebo + csDMARD and GSK3196165 90 mg + csDMARD Placebo + csDMARD and GSK3196165 150 mg + csDMARD GSK3196165 150mg + csDMARD Pooled Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 156 (5.13%)
    12 / 156 (7.69%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
    3 / 25 (12.00%)
    1 / 158 (0.63%)
    2 / 79 (2.53%)
         number of deaths (all causes)
    1
    1
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Rectal cancer
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 156 (0.64%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Aspartate aminotransferase increased
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 156 (0.64%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Alanine aminotransferase increased
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 156 (0.64%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Injury, poisoning and procedural complications
    Humerus fracture
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 158 (0.00%)
    0 / 79 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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 hypotension
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Congenital, familial and genetic disorders
    Gilbert's syndrome
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 156 (0.64%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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 disorders
    Peripheral arterial occlusive disease
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 156 (0.64%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Cardiac disorders
    Atrial fibrillation
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    2 / 156 (1.28%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Nervous system disorders
    Optic neuritis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 158 (0.63%)
    0 / 79 (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
    Sciatica
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 156 (0.64%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Cerebellar hemorrhage
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Blood and lymphatic system disorders
    Neutropenia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 156 (0.64%)
    2 / 156 (1.28%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 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
    General disorders and administration site conditions
    Drowning
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 156 (0.64%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Gastrointestinal disorders
    Obstructive pancreatitis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 156 (0.64%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Food poisoning
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    1 / 79 (1.27%)
         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
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    1 / 79 (1.27%)
         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
    Infections and infestations
    COVID-19
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    COVID-19 pneumonia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 156 (0.64%)
    2 / 156 (1.28%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    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
    Liver abscess
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Osteomyelitis bacterial
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Sepsis
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 GSK3196165 90mg + csDMARD Sarilumab 200mg + csDMARD Placebo + csDMARD and Sarilumab 200 mg + csDMARD Placebo + csDMARD and GSK3196165 90 mg + csDMARD Placebo + csDMARD and GSK3196165 150 mg + csDMARD GSK3196165 150mg + csDMARD Pooled Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    25 / 156 (16.03%)
    41 / 156 (26.28%)
    6 / 26 (23.08%)
    1 / 24 (4.17%)
    4 / 25 (16.00%)
    32 / 158 (20.25%)
    5 / 79 (6.33%)
    Investigations
    Alanine aminotransferase increased
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    2 / 156 (1.28%)
    10 / 156 (6.41%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    6 / 158 (3.80%)
    0 / 79 (0.00%)
         occurrences all number
    2
    11
    0
    0
    0
    6
    0
    Blood and lymphatic system disorders
    Neutropenia
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    2 / 156 (1.28%)
    11 / 156 (7.05%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    1 / 158 (0.63%)
    0 / 79 (0.00%)
         occurrences all number
    2
    12
    2
    0
    1
    1
    0
    General disorders and administration site conditions
    Injection site reaction
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    9 / 156 (5.77%)
    17 / 156 (10.90%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    10 / 158 (6.33%)
    0 / 79 (0.00%)
         occurrences all number
    17
    35
    0
    0
    0
    11
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    5 / 156 (3.21%)
    1 / 156 (0.64%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    10 / 158 (6.33%)
    0 / 79 (0.00%)
         occurrences all number
    6
    1
    0
    0
    0
    10
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 156 (0.00%)
    2 / 26 (7.69%)
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    0 / 79 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 156 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 158 (0.00%)
    5 / 79 (6.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    5
    Infections and infestations
    Latent tuberculosis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 156 (0.00%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 158 (0.00%)
    0 / 79 (0.00%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 156 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
    2 / 25 (8.00%)
    0 / 158 (0.00%)
    0 / 79 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    0
    Urinary tract infection
    alternative dictionary used: v25.0 25.0
         subjects affected / exposed
    8 / 156 (5.13%)
    6 / 156 (3.85%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    8 / 158 (5.06%)
    0 / 79 (0.00%)
         occurrences all number
    10
    6
    0
    0
    0
    9
    0

    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 introduce new medical device safety reporting wording, required in advance of roll out of pre-filled syringes to this study. Other minor corrections and clarifications added throughout the protocol

    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
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    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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