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    Clinical Trial Results:
    A Phase 3b/4 Randomized Double-Blind Study of 5 mg of Tofacitinib With and Without Methotrexate in Comparison to Adalimumab With Methotrexate in Subjects With Moderately to Severely Active Rheumatoid Arthritis

    Summary
    EudraCT number
    2014-000358-13
    Trial protocol
    CZ   EE   LT   LV   GB   ES   PL   BG   RO   DE   HR  
    Global end of trial date
    16 Dec 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    06 Dec 2017
    First version publication date
    06 Dec 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    A3921187
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02187055
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.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
    03 Feb 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Dec 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to compare the efficacy of 5 mg twice daily (BID) of tofacitinib (with and without background methotrexate [MTX]) to adalimumab with MTX as measured by American College of Rheumatology (ACR) criteria 50% improvement (ACR50) response rates at Month 6 and to compare the efficacy of 5 mg BID tofacitinib monotherapy versus 5 mg BID tofacitinib with MTX as measured by ACR50 response rates at Month 6.
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonisation Good Clinical Practice Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial participants. The final protocol and any amendments were reviewed and approved by the Institutional Review Board(s) and/or Independent Ethics Committee(s) at each of the investigational centres participating in the study.
    Background therapy
    Throughout the study subjects were to continue on their stable background arthritis therapy, which included MTX (or placebo MTX) and folic acid supplement and could have included nonsteroidal anti-inflammatory drugs, selective cyclooxygenase 2 inhibitors, opioids, cetaminophen, and/or low dose oral corticosteroids (less than or equal to 10 mg prednisone or equivalent per day).
    Evidence for comparator
    Adalimumab is a recombinant human immunoglobulin G1 monoclonal antibody specific for human tumor necrosis factor. It is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult subjects with moderately to severely active rheumatoid arthritis (RA). The currently approved dose is 40 mg every other week in adult subjects with RA.
    Actual start date of recruitment
    06 Aug 2014
    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: 43
    Country: Number of subjects enrolled
    Australia: 18
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 36
    Country: Number of subjects enrolled
    Bulgaria: 56
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Chile: 16
    Country: Number of subjects enrolled
    Czech Republic: 13
    Country: Number of subjects enrolled
    Estonia: 10
    Country: Number of subjects enrolled
    Israel: 12
    Country: Number of subjects enrolled
    Korea, Republic of: 37
    Country: Number of subjects enrolled
    Latvia: 4
    Country: Number of subjects enrolled
    Lithuania: 30
    Country: Number of subjects enrolled
    Mexico: 200
    Country: Number of subjects enrolled
    Peru: 17
    Country: Number of subjects enrolled
    Philippines: 43
    Country: Number of subjects enrolled
    Poland: 115
    Country: Number of subjects enrolled
    Romania: 46
    Country: Number of subjects enrolled
    Russian Federation: 111
    Country: Number of subjects enrolled
    South Africa: 60
    Country: Number of subjects enrolled
    Spain: 29
    Country: Number of subjects enrolled
    Taiwan: 16
    Country: Number of subjects enrolled
    Thailand: 15
    Country: Number of subjects enrolled
    Turkey: 3
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    United States: 201
    Worldwide total number of subjects
    1146
    EEA total number of subjects
    313
    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)
    992
    From 65 to 84 years
    152
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Confirmation of RA diagnosis and classification of RA was performed at the screening visit. Participants must have had a score of 6 or greater on the 2010 ACR/European League Against Rheumatism classification criteria for RA.

    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
    Tofacitinib 5 mg BID
    Arm description
    One active tofacitinib 5 mg tablet orally BID plus placebo MTX (prior dose) orally every week plus placebo adalimumab 40 mg subcutaneously (SC) every other week for up to 12 months.
    Arm type
    Experimental

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    CP-690550-10
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 active tofacitinib 5 mg tablet administered orally BID plus placebo MTX (prior dose) capsule(s) administered orally every week plus placebo adalimumab 40 mg injection administered subcutaneously (SC) every other week for up to 12 months.

    Arm title
    Tofacitinib 5 mg BID + MTX
    Arm description
    One active tofacitinib 5 mg tablet orally BID plus active MTX (prior dose) orally every week plus placebo adalimumab 40 mg SC every other week for up to 12 months.
    Arm type
    Experimental

    Investigational medicinal product name
    Tofacitinib and methotrexate
    Investigational medicinal product code
    CP-690550-10
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 active tofacitinib 5 mg tablet administered orally BID plus active MTX (prior dose) capsule(s) administered orally every week plus placebo adalimumab 40 mg injection administered SC every other week for up to 12 months.

    Arm title
    Adalimumab 40 mg + MTX
    Arm description
    One placebo tofacitinib 5 mg tablet orally BID plus active MTX (prior dose) orally every week plus active adalimumab 40 mg SC every other week for up to 12 months.
    Arm type
    Active comparator

    Investigational medicinal product name
    Adalimumab and methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 placebo tofacitinib 5 mg tablet administered orally BID plus active MTX (prior dose) capsule(s) administered orally every week plus active adalimumab 40 mg injection administered SC every other week for up to 12 months.

    Number of subjects in period 1
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Started
    384
    376
    386
    Completed
    315
    303
    312
    Not completed
    69
    73
    74
         No longer meets eligibility criteria
    -
    2
    -
         Protocol deviation
    9
    9
    4
         Lack of efficacy
    10
    3
    7
         Pregnancy
    3
    1
    -
         Adverse event, serious fatal
    2
    -
    -
         Adverse event, non-fatal
    21
    26
    36
         Consent withdrawn by subject
    11
    11
    11
         Unspecified
    5
    6
    3
         No longer willing to participate
    6
    8
    10
         Lost to follow-up
    2
    7
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tofacitinib 5 mg BID
    Reporting group description
    One active tofacitinib 5 mg tablet orally BID plus placebo MTX (prior dose) orally every week plus placebo adalimumab 40 mg subcutaneously (SC) every other week for up to 12 months.

    Reporting group title
    Tofacitinib 5 mg BID + MTX
    Reporting group description
    One active tofacitinib 5 mg tablet orally BID plus active MTX (prior dose) orally every week plus placebo adalimumab 40 mg SC every other week for up to 12 months.

    Reporting group title
    Adalimumab 40 mg + MTX
    Reporting group description
    One placebo tofacitinib 5 mg tablet orally BID plus active MTX (prior dose) orally every week plus active adalimumab 40 mg SC every other week for up to 12 months.

    Reporting group values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX Total
    Number of subjects
    384 376 386 1146
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    335 332 325 992
        From 65-84 years
    49 42 61 152
        85 years and over
    0 2 0 2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    49.7 ± 12.2 50.0 ± 13.4 50.7 ± 13.4 -
    Gender, Male/Female
    Units: Subjects
        Female
    319 311 320 950
        Male
    65 65 66 196

    End points

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    End points reporting groups
    Reporting group title
    Tofacitinib 5 mg BID
    Reporting group description
    One active tofacitinib 5 mg tablet orally BID plus placebo MTX (prior dose) orally every week plus placebo adalimumab 40 mg subcutaneously (SC) every other week for up to 12 months.

    Reporting group title
    Tofacitinib 5 mg BID + MTX
    Reporting group description
    One active tofacitinib 5 mg tablet orally BID plus active MTX (prior dose) orally every week plus placebo adalimumab 40 mg SC every other week for up to 12 months.

    Reporting group title
    Adalimumab 40 mg + MTX
    Reporting group description
    One placebo tofacitinib 5 mg tablet orally BID plus active MTX (prior dose) orally every week plus active adalimumab 40 mg SC every other week for up to 12 months.

    Primary: Percentage of Participants Achieving American College of Rheumatology Criteria 50% Improvement (ACR50) Response at Month 6

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    End point title
    Percentage of Participants Achieving American College of Rheumatology Criteria 50% Improvement (ACR50) Response at Month 6
    End point description
    ACR50 is a greater than or equal to (≥) 50 percent (%) improvement in tender joint count (TJC) or swollen joint count (SJC) and 50% improvement in 3 of the following 5 criteria: 1) physician's global assessment (PGA) of disease activity, 2) participant's assessment (PtGA) of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein (CRP) at each visit.
    End point type
    Primary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    384
    376
    386
    Units: Percentage of participants
        number (not applicable)
    38.28
    46.01
    43.78
    Statistical analysis title
    Analysis of ACR50 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    760
    Analysis specification
    Pre-specified
    Analysis type
    [1]
    P-value
    = 0.2101
    Method
    Normal approximation to proportions
    Parameter type
    Difference in response rate
    Point estimate
    -7.73
    Confidence interval
         level
    98.34%
         sides
    2-sided
         lower limit
    -16.29
         upper limit
    0.83
    Notes
    [1] - Non-inferiority was a treatment difference larger than -13% at the population level
    Statistical analysis title
    Analysis of ACR50 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    770
    Analysis specification
    Pre-specified
    Analysis type
    [2]
    P-value
    = 0.0512
    Method
    Normal approximation to proportions
    Parameter type
    Difference in response rate
    Point estimate
    -5.5
    Confidence interval
         level
    98.34%
         sides
    2-sided
         lower limit
    -13.98
         upper limit
    2.98
    Notes
    [2] - Non-inferiority was a treatment difference larger than -13% at the population level
    Statistical analysis title
    Analysis of ACR50 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    762
    Analysis specification
    Pre-specified
    Analysis type
    [3]
    P-value
    < 0.0001
    Method
    Normal approximation to proportions
    Parameter type
    Difference in response rate
    Point estimate
    2.23
    Confidence interval
         level
    98.34%
         sides
    2-sided
         lower limit
    -6.4
         upper limit
    10.86
    Notes
    [3] - Non-inferiority was a treatment difference larger than -13% at the population level

    Secondary: Change from Baseline in Simplified Disease Activity Index (SDAI) Value at Month 6

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    End point title
    Change from Baseline in Simplified Disease Activity Index (SDAI) Value at Month 6
    End point description
    SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 centimeter (cm) visual analogue scale (VAS) (higher scores indicate greater affection due to disease activity), and CRP (mg/dL). SDAI total score ranges from 0 to 86. SDAI less than or equal to (≤) 3.3 indicates disease remission, >3.4 to 11 indicates low disease activity, >11 to 26 indicates moderate disease activity, and >26 indicates high disease activity.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    355
    343
    345
    Units: Score on a scale
        least squares mean (standard error)
    -23.7 ± 0.62
    -26.6 ± 0.62
    -25.6 ± 0.62
    Statistical analysis title
    Analysis of SDAI at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.23
         upper limit
    4.41
    Statistical analysis title
    Analysis of SDAI at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.33
         upper limit
    3.49
    Statistical analysis title
    Analysis of SDAI at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    688
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.51
         upper limit
    0.68

    Secondary: Change from Baseline in Clinical Disease Activity Index (CDAI) Value at Month 6

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    End point title
    Change from Baseline in Clinical Disease Activity Index (CDAI) Value at Month 6
    End point description
    CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76. CDAI ≤2.8 indicates disease remission, >2.8 to 10 indicates low disease activity, >10 to 22 indicates moderate disease activity, and >22 indicates high disease activity.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    345
    347
    Units: Score on a scale
        least squares mean (standard error)
    -22.9 ± 0.61
    -25.5 ± 0.61
    -24.8 ± 0.61
    Statistical analysis title
    Analysis of CDAI at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    702
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.08
         upper limit
    4.18
    Statistical analysis title
    Analysis of CDAI at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    3.48
    Statistical analysis title
    Analysis of CDAI at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.24
         upper limit
    0.86

    Secondary: Change from Baseline in Disease Activity Score 28-4 (DAS28-4) Including CRP at Month 6

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    End point title
    Change from Baseline in Disease Activity Score 28-4 (DAS28-4) Including CRP at Month 6
    End point description
    DAS28-4 (CRP) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and CRP (mg/L) using the following: DAS28-4(CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014* PtGA (millimeters [mm]) + 0.96. Total score range: 0 to 9.4, higher score indicated higher disease activity. DAS28-4 (CRP) ≤3.2 indicates low disease activity, >3.2 to 5.1 indicates moderate to high disease activity, and less than (<) 2.6 indicates remission.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    355
    343
    345
    Units: Score on a scale
        least squares mean (standard error)
    -2.1 ± 0.07
    -2.5 ± 0.07
    -2.3 ± 0.07
    Statistical analysis title
    Analysis of DAS28-4 (CRP) at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.16
         upper limit
    0.5
    Statistical analysis title
    Analysis of DAS28-4 (CRP) at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.05
         upper limit
    0.39
    Statistical analysis title
    Analysis of DAS28-4 (CRP) at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    688
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.28
         upper limit
    0.06

    Secondary: Change from Baseline in Disease Activity Score 28-4 (DAS28-4) Including Erythrocyte Sedimentation Rate (ESR) at Month 6

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    End point title
    Change from Baseline in Disease Activity Score 28-4 (DAS28-4) Including Erythrocyte Sedimentation Rate (ESR) at Month 6
    End point description
    DAS28-4 (ESR) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and ESR (mm/hour) using the following: DAS28-4(ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014* PtGA (mm). Total score range: 0 to 9.4, higher score indicated higher disease activity. DAS28-3 (ESR) ≤3.2 indicates low disease activity, >3.2 to 5.1 indicates moderate to high disease activity, and <2.6 indicates remission.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    349
    342
    343
    Units: Score on a scale
        least squares mean (standard error)
    -2.1 ± 0.07
    -2.4 ± 0.07
    -2.4 ± 0.07
    Statistical analysis title
    Analysis of DAS28-4 (ESR) at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    691
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.15
         upper limit
    0.51
    Statistical analysis title
    Analysis of DAS28-4 (ESR) at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.1
         upper limit
    0.46
    Statistical analysis title
    Analysis of DAS28-4 (ESR) at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    685
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.23
         upper limit
    0.13

    Secondary: Percentage of Participants Achieving Observed American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean Remission Criteria at Month 6

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    End point title
    Percentage of Participants Achieving Observed American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean Remission Criteria at Month 6
    End point description
    To meet the ACR-EULAR Boolean remission criteria, a participant must satisfy all of the following: TJC ≤1 and SJC ≤1 (both based on a 28-joint assessment), CRP ≤1 mg/dL, and PtGA ≤1 on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity).
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    358
    346
    355
    Units: Percentage of participants
        number (not applicable)
    7.54
    8.67
    9.58
    Statistical analysis title
    Analysis of Remission Criteria at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -1.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.99
         upper limit
    2.56
    Statistical analysis title
    Analysis of Remission Criteria at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    713
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -1.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.59
         upper limit
    2.04
    Statistical analysis title
    Analysis of Remission Criteria at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    701
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -0.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.53
         upper limit
    3.4

    Secondary: Percentage of Participants Achieving SDAI ≤3.3 at Month 6

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    End point title
    Percentage of Participants Achieving SDAI ≤3.3 at Month 6
    End point description
    SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/dL). SDAI total score ranges from 0 to 86. SDAI ≤3.3 indicates disease remission.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    345
    348
    Units: Percentage of participants
        number (not applicable)
    10.64
    13.91
    14.37
    Statistical analysis title
    Analysis of SDAI ≤3.3 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    702
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -3.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.95
         upper limit
    1.15
    Statistical analysis title
    Analysis of SDAI ≤3.3 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -3.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.55
         upper limit
    1.43
    Statistical analysis title
    Analysis of SDAI ≤3.3 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    693
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    0.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.45
         upper limit
    5.14

    Secondary: Percentage of Participants Achieving CDAI ≤2.8 at Month 6

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    End point title
    Percentage of Participants Achieving CDAI ≤2.8 at Month 6
    End point description
    CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76. CDAI ≤2.8 indicates disease remission.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    358
    347
    350
    Units: Percentage of participants
        number (not applicable)
    10.89
    14.70
    14.57
    Statistical analysis title
    Analysis of CDAI ≤2.8 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -3.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.29
         upper limit
    0.94
    Statistical analysis title
    Analysis of CDAI ≤2.8 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    708
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -3.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.59
         upper limit
    1.48
    Statistical analysis title
    Analysis of CDAI ≤2.8 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    697
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    0.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.24
         upper limit
    5.47

    Secondary: Percentage of Participants Achieving DAS28-4 (ESR) <2.6 at Month 6

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    End point title
    Percentage of Participants Achieving DAS28-4 (ESR) <2.6 at Month 6
    End point description
    DAS28-4 (ESR) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and ESR (mm/hour) using the following: DAS28-4(ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014* PtGA (mm). Total score range: 0 to 9.4, higher score indicates higher disease activity. DAS28-4 (ESR) <2.6 indicates disease remission.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    353
    344
    346
    Units: Percentage of participants
        number (not applicable)
    11.33
    12.79
    13.58
    Statistical analysis title
    Analysis of DAS28-4 (ESR) <2.6 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    697
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -1.55
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.03
         upper limit
    2.93
    Statistical analysis title
    Analysis of DAS28-4 (ESR) <2.6 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    690
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -0.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.11
         upper limit
    4.18
    Statistical analysis title
    Analysis of DAS28-4 (ESR) <2.6 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -2.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.51
         upper limit
    2.47

    Secondary: Percentage of Participants Achieving DAS28-4 (CRP) <2.6 at Month 6

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    End point title
    Percentage of Participants Achieving DAS28-4 (CRP) <2.6 at Month 6
    End point description
    DAS28-4 (CRP) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and CRP (mg/L) using the following: DAS28-4(CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014* PtGA (mm) + 0.96. Total score range: 0 to 9.4, higher score indicates higher disease activity. DAS28-4 (CRP) <2.6 indicates remission.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    345
    348
    Units: Percentage of participants
        number (not applicable)
    22.69
    32.75
    30.17
    Statistical analysis title
    Analysis of DAS28-4 (CRP) <2.6 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    702
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -9.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.68
         upper limit
    -3.3
    Statistical analysis title
    Analysis of DAS28-4 (CRP) <2.6 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    693
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    2.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.86
         upper limit
    9.07
    Statistical analysis title
    Analysis of DAS28-4 (CRP) <2.6 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in remission rate
    Point estimate
    -6.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.94
         upper limit
    -0.83

    Secondary: Percentage of Participants Achieving SDAI ≤11 at Month 6

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    End point title
    Percentage of Participants Achieving SDAI ≤11 at Month 6
    End point description
    SDAI is the numerical sum of five outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity), and CRP (mg/dL). SDAI total score ranges from 0 to 86. SDAI ≤3.3 indicates disease remission, >3.4 to 11 indicates low disease activity.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    345
    348
    Units: Percentage of participants
        number (not applicable)
    46.78
    53.33
    51.15
    Statistical analysis title
    Analysis of SDAI ≤11 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    702
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -6.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.32
         upper limit
    0.84
    Statistical analysis title
    Analysis of SDAI ≤11 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    693
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    2.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.51
         upper limit
    9.68
    Statistical analysis title
    Analysis of SDAI ≤11 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -3.66
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.69
         upper limit
    3.37

    Secondary: Percentage of Participants Achieving CDAI ≤10 at Month 6

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    End point title
    Percentage of Participants Achieving CDAI ≤10 at Month 6
    End point description
    CDAI is the numerical sum of four outcome parameters: TJC and SJC both based on a 28-joint assessment, PtGA and PGA both assessed on a 0 to 10 cm VAS (higher scores indicate greater affection due to disease activity). CDAI total score ranges from 0 to 76. CDAI ≤2.8 indicates disease remission, >2.8 to 10 indicates low disease activity.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    358
    347
    350
    Units: Percentage of participants
        number (not applicable)
    45.53
    52.45
    50.00
    Statistical analysis title
    Analysis of CDAI ≤10 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -6.22
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.29
         upper limit
    0.85
    Statistical analysis title
    Analysis of CDAI ≤10 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    697
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    2.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.79
         upper limit
    9.39
    Statistical analysis title
    Analysis of CDAI ≤10 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    708
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -3.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.94
         upper limit
    3.09

    Secondary: Percentage of Participants Achieving DAS28-4 (ESR) ≤3.2 at Month 6

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    End point title
    Percentage of Participants Achieving DAS28-4 (ESR) ≤3.2 at Month 6
    End point description
    DAS28-4 (ESR) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and ESR (mm/hour) using the following: DAS28-4(ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014* PtGA (mm). Total score range: 0 to 9.4, higher score indicates higher disease activity. DAS28-4 (ESR) ≤3.2 indicates low disease activity.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    353
    344
    346
    Units: Percentage of participants
        number (not applicable)
    22.10
    28.49
    29.77
    Statistical analysis title
    Analysis of DAS28-4 (ESR) ≤3.2 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    697
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -6.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.05
         upper limit
    0
    Statistical analysis title
    Analysis of DAS28-4 (ESR) ≤3.2 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -6.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.9
         upper limit
    -0.87
    Statistical analysis title
    Analysis of DAS28-4 (ESR) ≤3.2 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    690
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -0.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.17
         upper limit
    5.44

    Secondary: Percentage of Participants Achieving DAS28-4 (CRP) ≤3.2 at Month 6

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    End point title
    Percentage of Participants Achieving DAS28-4 (CRP) ≤3.2 at Month 6
    End point description
    DAS28-4 (CRP) was calculated from the SJC and TJC (both based on a 28-joint assessment), PtGA (assessed on a 0 to 10 cm VAS; higher scores indicate greater affection due to disease activity) and CRP (mg/L) using the following: DAS28-4(CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014* PtGA + 0.96. Total score range: 0 to 9.4, higher score indicated higher disease activity. DAS28-4 (CRP) ≤3.2 indicates low disease activity.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    345
    348
    Units: Percentage of participants
        number (not applicable)
    44.54
    49.57
    50.86
    Statistical analysis title
    Analysis of DAS28-4 (CRP) ≤3.2 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    702
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -4.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.92
         upper limit
    2.18
    Statistical analysis title
    Analysis of DAS28-4 (CRP) ≤3.2 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -5.48
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.49
         upper limit
    1.52
    Statistical analysis title
    Analysis of DAS28-4 (CRP) ≤3.2 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    693
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in rresponse rate
    Point estimate
    -0.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.7
         upper limit
    6.47

    Secondary: Percentage of Participants Achieving American College of Rheumatology Criteria 20% Improvement (ACR20) Response at Month 6

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    End point title
    Percentage of Participants Achieving American College of Rheumatology Criteria 20% Improvement (ACR20) Response at Month 6
    End point description
    ACR20 response is a ≥20% improvement in TJC or SJC and 20% improvement in 3 of the following 5 criteria: 1) PGA of disease activity, 2) PtGA of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    354
    345
    349
    Units: Percentage of participants
        number (not applicable)
    70.06
    79.13
    77.65
    Statistical analysis title
    Analysis of ACR20 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -8.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.84
         upper limit
    -1.75
    Statistical analysis title
    Analysis of ACR20 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    694
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    2.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.22
         upper limit
    8.52
    Statistical analysis title
    Analysis of ACR20 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    703
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -6.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.72
         upper limit
    0.44

    Secondary: Percentage of Participants Achieving American College of Rheumatology Criteria 70% Improvement (ACR70) Response at Month 6

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    End point title
    Percentage of Participants Achieving American College of Rheumatology Criteria 70% Improvement (ACR70) Response at Month 6
    End point description
    ACR70 response is a ≥70% improvement in TJC or SJC and 70% improvement in 3 of the following 5 criteria: 1) PGA of disease activity, 2) PtGA of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP at each visit.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    356
    343
    349
    Units: Percentage of participants
        number (not applicable)
    19.66
    27.11
    22.64
    Statistical analysis title
    Analysis of ACR70 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -6.77
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.61
         upper limit
    -0.93
    Statistical analysis title
    Analysis of ACR70 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    692
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    4.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.68
         upper limit
    10.23
    Statistical analysis title
    Analysis of ACR70 at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -2.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.09
         upper limit
    3.1

    Secondary: Change From Baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI) at Month 6

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    End point title
    Change From Baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI) at Month 6
    End point description
    The HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dressing and grooming, arising, eating, walking, reach, grip, hygiene and other activities over the past week. Each activity category consists of 2 to 3 items. Each item is scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Any activity requiring assistance from another individual or the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    356
    348
    350
    Units: Units on a scale
        least squares mean (standard error)
    -0.52 ± 0.031
    -0.58 ± 0.031
    -0.54 ± 0.031
    Statistical analysis title
    Analysis of HAQ-DI at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.011
         upper limit
    0.148
    Statistical analysis title
    Analysis of HAQ-DI at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    706
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.054
         upper limit
    0.105
    Statistical analysis title
    Analysis of HAQ-DI at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.122
         upper limit
    0.037

    Secondary: Percentage of Participants Achieving an HAQ-DI Decrease of at Least 0.22 at Month 6

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    End point title
    Percentage of Participants Achieving an HAQ-DI Decrease of at Least 0.22 at Month 6
    End point description
    The HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dressing and grooming, arising, eating, walking, reach, grip, hygiene and other activities over the past week. Each activity category consists of 2 to 3 items. Each item is scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Any activity requiring assistance from another individual or the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score ranges from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. A decrease of 0.22 or more is considered a positive response.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    356
    348
    350
    Units: Percentage of participants
        number (not applicable)
    71.07
    75.57
    72.86
    Statistical analysis title
    Analysis of HAQ-DI 0.22 Decrease at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    706
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -4.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.68
         upper limit
    2.55
    Statistical analysis title
    Analysis of HAQ-DI 0.22 Decrease at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    706
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    -1.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.87
         upper limit
    5.44
    Statistical analysis title
    Analysis of HAQ-DI 0.22 Decrease at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Difference in response rate
    Point estimate
    2.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.72
         upper limit
    9.43

    Secondary: Change From Baseline in the Short-Form-36 (SF-36) Health Survey, Physical Component Score at Month 6

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    End point title
    Change From Baseline in the Short-Form-36 (SF-36) Health Survey, Physical Component Score at Month 6
    End point description
    The SF-36 health survey is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The health domains are aggregated into two summary scores known as the physical component summary (PCS) score and the mental component summary (MCS) score. Normalized domain scores, PCS and MCS scores are used in the analyses. The component and domain scores were scored using the United States (US) 1998 general population norms. The resulting norm-based T scores for both the SF-36 version 2 (v2) and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher PCS score represents better physical health status.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    355
    346
    349
    Units: Units on a scale
        least squares mean (standard error)
    6.7 ± 0.44
    7.9 ± 0.43
    7.8 ± 0.43
    Statistical analysis title
    Analysis of SF-36 PCS at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    701
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.28
         upper limit
    -0.11
    Statistical analysis title
    Analysis of SF-36 PCS at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.16
         upper limit
    0.01
    Statistical analysis title
    Analysis of SF-36 PCS at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    695
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.97
         upper limit
    1.2

    Secondary: Change From Baseline in the SF-36 Health Survey, Mental Component Score at Month 6

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    End point title
    Change From Baseline in the SF-36 Health Survey, Mental Component Score at Month 6
    End point description
    The SF-36 health survey is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The health domains are aggregated into two summary scores known as the PCS score and the MCS score. Normalized domain scores, PCS and MCS scores are used in the analyses. The component and domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher MCS score represents better physical health status.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    355
    346
    349
    Units: Units on a scale
        least squares mean (standard error)
    5.2 ± 0.52
    5.7 ± 0.51
    4.4 ± 0.51
    Statistical analysis title
    Analysis of SF-36 MCS at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    701
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.74
         upper limit
    0.85
    Statistical analysis title
    Analysis of SF-36 MCS at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.48
         upper limit
    2.11
    Statistical analysis title
    Analysis of SF-36 MCS at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    695
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.04
         upper limit
    2.56

    Secondary: Change From Baseline in the SF-36 Health Survey, Physical Functioning Domain Score at Month 6

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    End point title
    Change From Baseline in the SF-36 Health Survey, Physical Functioning Domain Score at Month 6
    End point description
    SF-36v2 acute is a 36-item measure evaluating 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 10 items of the physical functioning scale represent levels and kinds of limitations between extremes of physical activities, including lifting and carrying groceries; climbing stairs; bending, kneeling, or stooping; walking moderate distances; self-care limitations. The physical functioning items capture the presence and extent of physical limitations using a 3-level response continuum. The domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher physical functioning domain score represents better physical functioning.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    356
    348
    349
    Units: Units on a scale
        least squares mean (standard error)
    6.4 ± 0.52
    7.3 ± 0.52
    7.3 ± 0.52
    Statistical analysis title
    Analysis of SF-36 Physical Functioning at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.22
         upper limit
    0.39
    Statistical analysis title
    Analysis of SF-36 Physical Functioning at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.19
         upper limit
    0.42
    Statistical analysis title
    Analysis of SF-36 Physical Functioning at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    697
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.27
         upper limit
    1.34

    Secondary: Change From Baseline in the SF-36 Health Survey, Role Physical Domain Score at Month 6

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    End point title
    Change From Baseline in the SF-36 Health Survey, Role Physical Domain Score at Month 6
    End point description
    SF-36v2 acute is a 36-item measure evaluating 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 4-item role physical scale covers an array of physical health-related role limitations, including: a) limitations in the kind of work or other usual activities; b) reductions in the amount of time spent on work or other usual activities; c) difficulty performing work or other usual activities; and d) accomplishing less. Items in the role physical scale are answered on a 5-point scale. The domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher role physical domain score represents better role physical functioning.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    356
    347
    350
    Units: Units on a scale
        least squares mean (standard error)
    6.7 ± 0.47
    7.0 ± 0.47
    6.3 ± 0.47
    Statistical analysis title
    Analysis of SF-36 Role Physical at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    703
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.52
         upper limit
    0.87
    Statistical analysis title
    Analysis of SF-36 Role Physical at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    706
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    1.58
    Statistical analysis title
    Analysis of SF-36 Role Physical at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    697
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.47
         upper limit
    1.91

    Secondary: Change From Baseline in the SF-36 Health Survey, Bodily Pain Domain Score at Month 6

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    End point title
    Change From Baseline in the SF-36 Health Survey, Bodily Pain Domain Score at Month 6
    End point description
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The bodily pain scale comprises of 2 items pertaining to the intensity of bodily pain and extent of interference with normal work activities. The domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher bodily pain domain score represents less bodily pain.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    356
    348
    350
    Units: Units on a scale
        least squares mean (standard error)
    8.2 ± 0.48
    10.3 ± 0.48
    9.9 ± 0.48
    Statistical analysis title
    Analysis of SF-36 Bodily Pain at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.25
         upper limit
    -0.8
    Statistical analysis title
    Analysis of SF-36 Bodily Pain at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    706
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -1.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.91
         upper limit
    -0.47
    Statistical analysis title
    Analysis of SF-36 Bodily Pain at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.89
         upper limit
    1.55

    Secondary: Change From Baseline in the SF-36 Health Survey, General Health Domain Score at Month 6

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    End point title
    Change From Baseline in the SF-36 Health Survey, General Health Domain Score at Month 6
    End point description
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The general health scale consists of 5 items including a rating of health and 4 items addressing the respondent’s view and expectations of his or her health. The domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher general health domain score represents better general health perceptions.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    347
    350
    Units: Units on a scale
        least squares mean (standard error)
    5.1 ± 0.44
    6.3 ± 0.44
    5.4 ± 0.44
    Statistical analysis title
    Analysis of SF-36 General Health at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.27
         upper limit
    -0.05
    Statistical analysis title
    Analysis of SF-36 General Health at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    0.82
    Statistical analysis title
    Analysis of SF-36 General Health at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    697
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.25
         upper limit
    1.98

    Secondary: Change From Baseline in the SF-36 Health Survey, Vitality Domain Score at Month 6

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    End point title
    Change From Baseline in the SF-36 Health Survey, Vitality Domain Score at Month 6
    End point description
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 4-item measure of vitality captures a broad range of subjective evaluations of well-being from feelings of tiredness and being worn out to feeling full of energy all or most of the time. The domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher vitality domain score represents better vitality.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    348
    350
    Units: Units on a scale
        least squares mean (standard error)
    5.6 ± 0.48
    6.1 ± 0.47
    5.7 ± 0.47
    Statistical analysis title
    Analysis of SF-36 Vitality at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.71
         upper limit
    0.68
    Statistical analysis title
    Analysis of SF-36 Vitality at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.33
         upper limit
    1.05
    Statistical analysis title
    Analysis of SF-36 Vitality at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.83
         upper limit
    1.57

    Secondary: Change From Baseline in the SF-36 Health Survey, Social Functioning Domain Score at Month 6

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    End point title
    Change From Baseline in the SF-36 Health Survey, Social Functioning Domain Score at Month 6
    End point description
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 2-item social functioning scale assesses health-related effects on quantity and quality of social activities. The domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher social functioning domain score represents better social functioning.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    348
    350
    Units: Units on a scale
        least squares mean (standard error)
    6.3 ± 0.52
    7.2 ± 0.52
    6.2 ± 0.52
    Statistical analysis title
    Analysis of SF-36 Social Functioning at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    0.45
    Statistical analysis title
    Analysis of SF-36 Social Functioning at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    707
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.13
         upper limit
    1.51
    Statistical analysis title
    Analysis of SF-36 Social Functioning at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.26
         upper limit
    2.39

    Secondary: Change From Baseline in the SF-36 Health Survey, Role Emotional Domain Score at Month 6

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    End point title
    Change From Baseline in the SF-36 Health Survey, Role Emotional Domain Score at Month 6
    End point description
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 3-item role emotional scale assesses mental health-related role limitations in terms of a) time spent in work or other usual activities; b) amount of work or activities accomplished; c) care with which work or other activities were performed. All 3 items are answered on a 5-point scale. The domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher role emotional domain score represents better role emotional functioning.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    356
    347
    350
    Units: Units on a scale
        least squares mean (standard error)
    6.7 ± 0.58
    7.7 ± 0.58
    6.0 ± 0.58
    Statistical analysis title
    Analysis of SF-36 Role Emotional at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    703
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.54
         upper limit
    0.39
    Statistical analysis title
    Analysis of SF-36 Role Emotional at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    697
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.3
         upper limit
    3.24
    Statistical analysis title
    Analysis of SF-36 Role Emotional at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    706
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.76
         upper limit
    2.16

    Secondary: Change From Baseline in the SF-36 Health Survey, Mental Health Domain Score at Month 6

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    End point title
    Change From Baseline in the SF-36 Health Survey, Mental Health Domain Score at Month 6
    End point description
    The SF-36v2 acute is a 36-item measure that evaluates 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 5-item mental health scale includes 1 or more items from each of 4 major mental health dimensions: anxiety, depression, loss of behavioral/emotional control, and psychological well-being. All items are answered on a 5-point scale. The domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 v2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. A higher mental health domain score represents better mental health functioning.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    356
    348
    350
    Units: Units on a scale
        least squares mean (standard error)
    5.3 ± 0.52
    5.5 ± 0.52
    5.0 ± 0.52
    Statistical analysis title
    Analysis of SF-36 Mental Health at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.55
         upper limit
    1.08
    Statistical analysis title
    Analysis of SF-36 Mental Health at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.78
         upper limit
    1.86
    Statistical analysis title
    Analysis of SF-36 Mental Health at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    706
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.01
         upper limit
    1.62

    Secondary: Change From Baseline in the Work Productivity and Activity Impairment (WPAI) Questionnaire at Month 6

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    End point title
    Change From Baseline in the Work Productivity and Activity Impairment (WPAI) Questionnaire at Month 6
    End point description
    The WPAI: Rheumatoid Arthritis is a 6 item questionnaire that is specific for rheumatoid arthritis and yields four types of scores: absenteeism, presenteesism (impairment at work/reduced job effectiveness), work productivity loss and activity impairment. WPAI outcomes are expressed as impairment percentages ranging from 0 to 100, with higher numbers indicating greater impairment and less productivity.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    341
    343
    Units: Percentage of impairment
    least squares mean (standard error)
        Work hours missed due to problems
    -2.62 ± 0.717
    -2.19 ± 0.700
    -1.75 ± 0.741
        Work hours missed other reason
    0.14 ± 1.019
    0.43 ± 0.991
    -0.77 ± 1.059
        Hours worked in past 7 days
    4.13 ± 1.729
    -0.82 ± 1.672
    1.28 ± 1.788
        Problems affecting productivity
    -1.94 ± 0.228
    -2.14 ± 0.224
    -1.95 ± 0.232
        Problem affecting daily activities
    -2.24 ± 0.137
    -2.47 ± 0.138
    -2.24 ± 0.139
        % work time missed due to health
    -4.51 ± 1.790
    -3.41 ± 1.794
    -1.87 ± 1.831
        % impairment while working due to health
    -19.38 ± 2.276
    -21.44 ± 2.235
    -19.52 ± 2.320
        % overall work impairment due to health
    -20.16 ± 2.663
    -22.27 ± 2.638
    -21.87 ± 2.710
        % activity impairment due to health
    -22.36 ± 1.375
    -24.74 ± 1.383
    -22.45 ± 1.394
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Work hours missed due to problems
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.279
         upper limit
    1.427
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Work hours missed due to problems
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.783
         upper limit
    1.044
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Work hours missed due to problems
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.349
         upper limit
    1.462
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Work hours missed other reason
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.928
         upper limit
    2.346
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Work hours missed other reason
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.832
         upper limit
    3.64
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Work hours missed other reason
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.52
         upper limit
    3.911
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Hours worked in past 7 days
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    4.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.52
         upper limit
    9.37
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Hours worked in past 7 days
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.85
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.736
         upper limit
    7.43
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Hours worked in past 7 days
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -2.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.65
         upper limit
    2.454
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Problems affecting productivity
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.373
         upper limit
    0.786
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Problems affecting productivity
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.578
         upper limit
    0.607
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Problems affecting productivity
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.784
         upper limit
    0.4
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Problem affecting daily activities
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.112
         upper limit
    0.587
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Problem affecting daily activities
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.341
         upper limit
    0.357
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    Problem affecting daily activities
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.582
         upper limit
    0.122
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % work time missed due to health
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.748
         upper limit
    3.553
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % work time missed due to health
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -2.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.339
         upper limit
    2.067
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % work time missed due to health
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -1.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.283
         upper limit
    3.207
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % impairment while working due to health
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.726
         upper limit
    7.858
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % impairment while working due to health
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.777
         upper limit
    6.068
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % impairment while working due to health
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -1.92
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.839
         upper limit
    3.998
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % overall work impairment due to health
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.664
         upper limit
    8.877
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % overall work impairment due to health
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.164
         upper limit
    8.58
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % overall work impairment due to health
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.307
         upper limit
    6.51
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % activity impairment due to health
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    698
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    2.38
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.118
         upper limit
    5.873
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % activity impairment due to health
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.411
         upper limit
    3.573
    Statistical analysis title
    Analysis of WAPI at Month 6
    Statistical analysis description
    % activity impairment due to health
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -2.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.818
         upper limit
    1.225

    Secondary: Change From Baseline in the EuroQol European Quality of Life-5 Dimensions (EuroQol EQ-5D) at Month 6

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    End point title
    Change From Baseline in the EuroQol European Quality of Life-5 Dimensions (EuroQol EQ-5D) at Month 6
    End point description
    The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    348
    351
    Units: Units on a scale
    least squares mean (standard error)
        Utility score
    0.20 ± 0.013
    0.22 ± 0.013
    0.22 ± 0.013
        Mobility score
    -0.29 ± 0.027
    -0.26 ± 0.027
    -0.28 ± 0.027
        Self-care score
    -0.27 ± 0.028
    -0.33 ± 0.028
    -0.32 ± 0.028
        Usual activities score
    -0.24 ± 0.029
    -0.26 ± 0.029
    -0.30 ± 0.029
        Pain/discomfort score
    -0.32 ± 0.026
    -0.34 ± 0.026
    -0.37 ± 0.026
        Anxiety/depression score
    -0.21 ± 0.029
    -0.24 ± 0.029
    -0.22 ± 0.029
        VAS score
    20.84 ± 1.100
    20.98 ± 1.100
    19.61 ± 1.100
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Utility score
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.057
         upper limit
    0.011
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Utility score
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    708
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.054
         upper limit
    0.013
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Utility score
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.031
         upper limit
    0.036
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Mobility score
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.098
         upper limit
    0.042
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Mobility score
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    708
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.079
         upper limit
    0.06
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Mobility score
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.051
         upper limit
    0.089
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Self-care score
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.014
         upper limit
    0.127
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Self-care score
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    708
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.027
         upper limit
    0.114
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Self-care score
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.083
         upper limit
    0.058
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Usual activities score
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.062
         upper limit
    0.084
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Usual activities score
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    708
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.018
         upper limit
    0.129
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Usual activities score
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.029
         upper limit
    0.118
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Pain/discomfort score
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.041
         upper limit
    0.091
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Pain/discomfort score
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    708
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.015
         upper limit
    0.116
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Pain/discomfort score
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.041
         upper limit
    0.091
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Anxiety/depression score
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.046
         upper limit
    0.103
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Anxiety/depression score
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    708
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.066
         upper limit
    0.083
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    Anxiety/depression score
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.094
         upper limit
    0.055
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    VAS score
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.934
         upper limit
    2.648
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    VAS score
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    708
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.556
         upper limit
    4.016
    Statistical analysis title
    Analysis of EuroQol EQ-5D at Month 6
    Statistical analysis description
    VAS score
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    699
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.425
         upper limit
    4.171

    Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Total Score at Month 6

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    End point title
    Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale Total Score at Month 6
    End point description
    FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). The larger the participant’s response (with the exception of 2 negatively stated), the greater the participant’s fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant’s response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Tofacitinib 5 mg BID Tofacitinib 5 mg BID + MTX Adalimumab 40 mg + MTX
    Number of subjects analysed
    357
    348
    352
    Units: Units on a scale
        least squares mean (standard error)
    7.14 ± 0.500
    7.59 ± 0.498
    6.07 ± 0.499
    Statistical analysis title
    Analysis of FACIT-F at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Tofacitinib 5 mg BID + MTX
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.706
         upper limit
    0.808
    Statistical analysis title
    Analysis of FACIT-F at Month 6
    Comparison groups
    Tofacitinib 5 mg BID v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    709
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.178
         upper limit
    2.325
    Statistical analysis title
    Analysis of FACIT-F at Month 6
    Comparison groups
    Tofacitinib 5 mg BID + MTX v Adalimumab 40 mg + MTX
    Number of subjects included in analysis
    700
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    LS mean difference
    Point estimate
    1.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.266
         upper limit
    2.779

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs were assessed from informed consent up to at least 28 calendar days after last dose of investigational product. AEs were recorded from the time the subject has taken at least one dose of study treatment through last subject visit.
    Adverse event reporting additional description
    An event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Tofacitinib 5 mg BID
    Reporting group description
    One active tofacitinib 5 mg tablet orally BID plus placebo MTX (prior dose) orally every week plus placebo adalimumab 40 mg subcutaneously (SC) every other week for up to 12 months.

    Reporting group title
    Adalimumab 40 mg + MTX
    Reporting group description
    One placebo tofacitinib 5 mg tablet orally BID plus active MTX (prior dose) orally every week plus active adalimumab 40 mg SC every other week for up to 12 months.

    Reporting group title
    Tofacitinib 5 mg BID + MTX
    Reporting group description
    One active tofacitinib 5 mg tablet orally BID plus active MTX (prior dose) orally every week plus placebo adalimumab 40 mg SC every other week for up to 12 months.

    Serious adverse events
    Tofacitinib 5 mg BID Adalimumab 40 mg + MTX Tofacitinib 5 mg BID + MTX
    Total subjects affected by serious adverse events
         subjects affected / exposed
    35 / 384 (9.11%)
    24 / 386 (6.22%)
    27 / 376 (7.18%)
         number of deaths (all causes)
    2
    1
    0
         number of deaths resulting from adverse events
    2
    0
    0
    Vascular disorders
    Hypertensive emergency
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anogenital warts
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enteropathy-associated T-cell lymphoma
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lobular breast carcinoma in situ
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Unintended pregnancy
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    2 / 384 (0.52%)
    1 / 386 (0.26%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 384 (0.00%)
    2 / 386 (0.52%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Exposure via father
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    3 / 376 (0.80%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wolff-Parkinson-White syndrome
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 384 (0.26%)
    1 / 386 (0.26%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 384 (0.26%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid lung
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Pancytopenia
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebellar infarction
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertonia
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radicular syndrome
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Corneal thinning
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Necrotising retinitis
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Diabetic nephropathy
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 384 (0.00%)
    2 / 386 (0.52%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    2 / 384 (0.52%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone disorder
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Atypical pneumonia
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    3 / 384 (0.78%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridial sepsis
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis bacterial
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis tuberculous
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    2 / 376 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salpingo-oophoritis
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 384 (0.00%)
    1 / 386 (0.26%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Varicella zoster virus infection
         subjects affected / exposed
    1 / 384 (0.26%)
    0 / 386 (0.00%)
    0 / 376 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis with abscess
         subjects affected / exposed
    0 / 384 (0.00%)
    0 / 386 (0.00%)
    1 / 376 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Tofacitinib 5 mg BID Adalimumab 40 mg + MTX Tofacitinib 5 mg BID + MTX
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    51 / 384 (13.28%)
    69 / 386 (17.88%)
    72 / 376 (19.15%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    8 / 384 (2.08%)
    26 / 386 (6.74%)
    23 / 376 (6.12%)
         occurrences all number
    8
    38
    28
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    22 / 384 (5.73%)
    18 / 386 (4.66%)
    16 / 376 (4.26%)
         occurrences all number
    28
    23
    19
    Upper respiratory tract infection
         subjects affected / exposed
    25 / 384 (6.51%)
    29 / 386 (7.51%)
    37 / 376 (9.84%)
         occurrences all number
    35
    37
    48

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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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