Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39231   clinical trials with a EudraCT protocol, of which   6427   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3B/4 Randomized Double Blind Placebo Controlled Study of Methotrexate (MTX) Withdrawal in Subjects With Rheumatoid Arthritis (RA) Treated With Tofacitinib 11mg Modified Release (MR) Formulation

    Summary
    EudraCT number
    2016-001825-15
    Trial protocol
    SK   BG   BE   DE   GB   PL   ES   CZ   HU   IT  
    Global end of trial date
    17 Dec 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    18 Dec 2019
    First version publication date
    18 Dec 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    A3921192
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., +1 18007181021, 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
    30 May 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Nov 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Dec 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy of tofacitinib MR 11mg monotherapy to tofacitinib MR 11mg with continued MTX, as measured by the change in the Disease Activity Score utilizing 4 components including erythrocyte sedimentation rate (DAS28-4 [ESR]) from randomization (at Week 24) to the end of the double-blind MTX withdrawal phase (at Week 48).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Sep 2016
    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
    Mexico: 25
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Bulgaria: 49
    Country: Number of subjects enrolled
    Czech Republic: 60
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Hungary: 30
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 17
    Country: Number of subjects enrolled
    Philippines: 12
    Country: Number of subjects enrolled
    Poland: 130
    Country: Number of subjects enrolled
    Russian Federation: 37
    Country: Number of subjects enrolled
    Slovakia: 22
    Country: Number of subjects enrolled
    South Africa: 2
    Country: Number of subjects enrolled
    Spain: 15
    Country: Number of subjects enrolled
    United Kingdom: 9
    Country: Number of subjects enrolled
    United States: 276
    Worldwide total number of subjects
    694
    EEA total number of subjects
    318
    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)
    508
    From 65 to 84 years
    184
    85 years and over
    2

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The study was conducted at 136 sites in the 16 countries from 01 September 2016 to 17 December 2018.

    Pre-assignment
    Screening details
    A total of 873 subjects were screened in the open label phase. 694 subjects were treated.

    Period 1
    Period 1 title
    Open Label Phase (24 Weeks)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Open Label: Tofacitinib 11 mg + Methotrexate
    Arm description
    Subjects with moderate to severe rheumatoid arthritis (RA) and who were insufficiently responding to their stable dose of methotrexate treatment previous to enrollment in this study, received Tofacitinib modified release (MR) 11 milligram (mg) tablet once daily (QD) with methotrexate (as background therapy) at their previous stable dose for 24 weeks in open label phase (OL).
    Arm type
    Experimental

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Tofacitinib MR 11 mg tablet QD for 24 weeks in open label phase.

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received methotrexate at their previous stable dose for 24 weeks in open label phase.

    Number of subjects in period 1
    Open Label: Tofacitinib 11 mg + Methotrexate
    Started
    694
    Completed
    623
    Not completed
    71
         Protocol deviation
    5
         Insufficient Clinical Response
    7
         Adverse event, non-fatal
    39
         Unspecified
    4
         Consent withdrawn by subject
    6
         Medication error,no linked adverse event
    2
         Lost to follow-up
    8
    Period 2
    Period 2 title
    Double Blind Phase (24 Weeks)
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Investigator, Subject

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo
    Arm description
    Subjects with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
    Arm type
    Experimental

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Tofacitinib MR 11 mg tablet QD for 24 weeks in double blind phase.

    Investigational medicinal product name
    Methotrexate Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received methotrexate matching placebo at their previous stable dose for 24 weeks in double blind phase.

    Arm title
    Double Blind: Tofacitinib 11 mg + Methotrexate
    Arm description
    Subjects with LDA at the end of open label phase received Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.
    Arm type
    Experimental

    Investigational medicinal product name
    Tofacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received Tofacitinib MR 11 mg tablet QD for 24 weeks in double blind phase.

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received methotrexate at their previous stable dose for 24 weeks in double blind phase.

    Number of subjects in period 2
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Started
    267
    266
    Treated
    264
    266
    Completed
    238
    247
    Not completed
    29
    19
         Protocol deviation
    5
    2
         Randomized but not Treated
    3
    -
         Insufficient Clinical Response
    6
    1
         Adverse event, serious fatal
    -
    2
         Screen Failure
    1
    -
         Adverse event, non-fatal
    6
    6
         Unspecified
    2
    5
         Consent withdrawn by subject
    5
    2
         Lost to follow-up
    1
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Open Label: Tofacitinib 11 mg + Methotrexate
    Reporting group description
    Subjects with moderate to severe rheumatoid arthritis (RA) and who were insufficiently responding to their stable dose of methotrexate treatment previous to enrollment in this study, received Tofacitinib modified release (MR) 11 milligram (mg) tablet once daily (QD) with methotrexate (as background therapy) at their previous stable dose for 24 weeks in open label phase (OL).

    Reporting group values
    Open Label: Tofacitinib 11 mg + Methotrexate Total
    Number of subjects
    694 694
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    508 508
        From 65-84 years
    184 184
        85 years and over
    2 2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    56.77 ± 11.83 -
    Sex: Female, Male
    Units: Subjects
        Female
    532 532
        Male
    162 162
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0
        Asian
    37 37
        Native Hawaiian or Other Pacific Islander
    0 0
        Black or African American
    33 33
        White
    594 594
        More than one race
    0 0
        Other
    30 30
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    59 59
        Not Hispanic or Latino
    635 635
        Unknown or Not Reported
    0 0

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Open Label: Tofacitinib 11 mg + Methotrexate
    Reporting group description
    Subjects with moderate to severe rheumatoid arthritis (RA) and who were insufficiently responding to their stable dose of methotrexate treatment previous to enrollment in this study, received Tofacitinib modified release (MR) 11 milligram (mg) tablet once daily (QD) with methotrexate (as background therapy) at their previous stable dose for 24 weeks in open label phase (OL).
    Reporting group title
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo
    Reporting group description
    Subjects with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.

    Reporting group title
    Double Blind: Tofacitinib 11 mg + Methotrexate
    Reporting group description
    Subjects with LDA at the end of open label phase received Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.

    Primary: Double Blind Phase: Change From Randomization in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 48
    End point description
    DAS28 is a measure of disease activity in subjects with RA. DAS28-4 (ESR) was calculated from swollen joint count(SJC) and tender/painful joint count (TJC) using 28 joints count, ESR (millimeters per hour [mm/hr]) & subject global assessment of arthritis (PtGA) on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0(none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (<=) 3.2 implied low disease activity and greater than (>) 3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity & DAS28-4 (ESR) less than (<) 2.6 implied remission. DAS28-4 (ESR) =0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*In(ESR in mm/ hour) + 0.014*PtGA in mm; ln =natural logarithm, sqrt =square root of. FAS-DB. Overall number of subjects analyzed=subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    235
    237
    Units: units on a scale
        least squares mean (standard error)
    0.33 ± 0.07
    0.03 ± 0.07
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Linear mixed-effect model of repeated measures (MMRM) was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline DAS28-4 (ESR) value as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    472
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    P-value
    = 0.0005 [2]
    Method
    MMRM
    Parameter type
    Least Square (LS) Mean Difference
    Point estimate
    0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.12
         upper limit
    0.48
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Notes
    [1] - Non-inferiority of Tofacitinib monotherapy to Tofacitinib with continued MTX treatment was concluded if the upper bound of 95% 2-sided CI for difference between the 2 arms (Tofacitinib monotherapy arm - Tofacitinib with MTX arm) was lower than 0.6.
    [2] - The reported p-value (one-sided) is for the non-inferiority test at the margin of 0.6

    Secondary: Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in DAS28-4 ESR at Week 36
    End point description
    DAS28 is a measure of disease activity in subjects with RA. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition).Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (ESR) <2.6 implied remission. DAS28-4(ESR) =0.56*sqrt(TJC28) +0.28*sqrt(SJC28) +0.70*In(ESR in mm/hour)+ 0.014*PtGA in mm. Double-blind period full analysis set(FAS-DB) included all subjects who received at least 1 dose of investigational drug during the OL phase,were randomized & received at least 1 dose of the randomized investigational drug regimen during DB phase.Overall number of subjects analyzed=subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    253
    253
    Units: units on a scale
        least squares mean (standard error)
    0.40 ± 0.07
    0.18 ± 0.07
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline DAS28-4 (ESR) value as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    506
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    0.22
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.03
         upper limit
    0.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive protein [CRP]) at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in DAS28-4 (C-reactive protein [CRP]) at Weeks 36 and 48
    End point description
    DAS28 is a measure of disease activity in subjects with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (milligrams per liter [mg/L]) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) <= 3.2 implied low disease activity and > 3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (CRP) < 2.6 implied remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96. FAS-DB was analyzed. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: units on a scale
    least squares mean (standard error)
        Change at Week 36 (n =250 , 254)
    0.38 ± 0.06
    0.13 ± 0.06
        Change at Week 48 (n =231 , 235)
    0.29 ± 0.06
    0.01 ± 0.06
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment -by-visit interaction, prior use of a bDMARD and baseline DAS28-4 (CRP) value as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    0.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.08
         upper limit
    0.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment -by-visit interaction, prior use of a bDMARD and baseline DAS28-4 (CRP) value as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    0.28
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.11
         upper limit
    0.45
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09

    Secondary: Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in Clinical Disease Activity Index (CDAI) at Weeks 36 and 48
    End point description
    CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and physician global assessment of arthritis (PhyGA). PtGA and PhyGA both were assessed on 0-10 centimeter (cm) VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of <=10 indicated low disease activity and a score of <= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm). FAS-DB was analyzed. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: units on a scale
    least squares mean (standard error)
        Change at Week 36 (n =254, 259)
    3.58 ± 0.49
    1.84 ± 0.48
        Change at Week 48 (n =238, 244)
    2.97 ± 0.48
    0.84 ± 0.47
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline CDAI value as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    1.74
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    3.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.68
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline CDAI value as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    2.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.83
         upper limit
    3.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66

    Secondary: Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in Simplified Disease Activity Index (SDAI) at Weeks 36 and 48
    End point description
    SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity. SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity). SDAI score of <=11 indicates low disease activity and a score of <=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL). FAS-DB was analyzed. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: units on a scale
    least squares mean (standard error)
        Change at Week 36 (n =249, 254)
    3.83 ± 0.52
    1.88 ± 0.51
        Change at Week 48 (n =231, 235)
    3.16 ± 0.50
    0.94 ± 0.49
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline SDAI value as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    1.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.53
         upper limit
    3.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.72
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD and baseline SDAI value as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    2.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.86
         upper limit
    3.59
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.69

    Secondary: Double Blind Phase: Percentage of Subjects With Low Disease Activity (LDA) Assessed by DAS28-4 (ESR) Less Than or Equal to (<=) 3.2 at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects With Low Disease Activity (LDA) Assessed by DAS28-4 (ESR) Less Than or Equal to (<=) 3.2 at Weeks 36 and 48
    End point description
    DAS28 is a measure of disease activity in subjects with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicated worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (ESR) <2.6 implied remission. DAS28-4 (ESR) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*In(ESR in mm/ hour) + 0.014*PtGA in mm. Non-responder imputation (NRI) method was used to impute missing data. FAS-DB included all subjects who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase.
    End point type
    Secondary
    End point timeframe
    Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    42.42
    48.12
        Week 48
    45.08
    49.62
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -5.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.15
         upper limit
    2.76
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -4.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.04
         upper limit
    3.94

    Secondary: Double Blind Phase: Percentage of Subjects With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects With LDA Assessed by DAS28-4 (CRP) <=3.2 at Weeks 36 and 48
    End point description
    DAS28 is a measure of disease activity in subjects with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/dL) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (CRP) <2.6 implied remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96. NRI method was used to impute missing data. FAS-DB included all subjects who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase.
    End point type
    Secondary
    End point timeframe
    Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    65.53
    70.68
        Week 48
    65.91
    74.44
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -5.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.07
         upper limit
    2.77
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment -by-visit interaction, prior use of a biological DMARD and baseline DAS28-4 (CRP) value as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -8.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -16.28
         upper limit
    -0.76

    Secondary: Double Blind Phase: Percentage of Subjects With LDA Assessed by CDAI <=10 at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects With LDA Assessed by CDAI <=10 at Weeks 36 and 48
    End point description
    CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of <=10 indicated low disease activity and a score of <= 2.8 indicated remission. Percentage of subjects with CDAI <=10 were reported. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm). NRI method was used to impute missing data. FAS-DB included all subjects who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase.
    End point type
    Secondary
    End point timeframe
    Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    66.29
    73.68
        Week 48
    65.15
    77.07
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -7.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.17
         upper limit
    0.38
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -11.91
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -19.56
         upper limit
    -4.26

    Secondary: Double Blind Phase: Percentage of Subjects With LDA Assessed by SDAI <=11 at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects With LDA Assessed by SDAI <=11 at Weeks 36 and 48
    End point description
    SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of <=11 indicates low disease activity and a score of <=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL). NRI method was used to impute missing data. FAS-DB included all subjects who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase.
    End point type
    Secondary
    End point timeframe
    Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    66.29
    73.31
        Week 48
    66.29
    76.32
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -7.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.81
         upper limit
    0.77
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -10.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.68
         upper limit
    -2.37

    Secondary: Double Blind Phase: Percentage of Subjects With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Weeks 36 and 48
    End point description
    ACR-EULAR Boolean remission was when a subject satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), CRP (in mg/dL), and PtGA (VAS: 0 cm [very well] to 10 cm [worst], higher scores indicated worse health condition) and all scores were <=1. NRI method was used to impute missing data. FAS-DB included all subjects who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase.
    End point type
    Secondary
    End point timeframe
    Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    15.53
    24.06
        Week 48
    22.35
    23.68
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -8.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.27
         upper limit
    -1.78
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -1.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.5
         upper limit
    5.83

    Secondary: Double Blind Phase: Percentage of Subjects With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects With Remission Assessed by DAS28-4 (ESR) Less Than [<] 2.6 at Weeks 36 and 48
    End point description
    DAS28 is a measure of disease activity in subjects with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) <= 3.2 implied low disease activity & >3.2 to <=5.1 implied moderate disease activity,>5.1 implied high disease activity, & DAS28-4 (ESR) <2.6 implied remission. DAS28-4 (ESR)=0.56*sqrt(TJC28)+0.28*sqrt(SJC28) + 0.70*In(ESR in mm/ hour) + 0.014*PtGA in mm. Percentage of subjects with DAS remission (DAS28-4-ESR<2.6) were reported in this endpoint. NRI method was used to impute missing data. FAS-DB was analyzed.
    End point type
    Secondary
    End point timeframe
    Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    20.45
    28.57
        Week 48
    23.86
    30.08
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -8.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.4
         upper limit
    -0.82
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -6.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.74
         upper limit
    1.32

    Secondary: Double Blind Phase: Percentage of Subjects With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 48 and 36

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects With Remission Assessed by DAS28-4 (CRP) <2.6 at Weeks 48 and 36
    End point description
    DAS28 is a measure of disease activity in subjects with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and PtGA on a 100 mm VAS (VAS: scores ranging from 0 mm [very well] to 100 mm [worst], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) <=3.2 implied low disease activity and >3.2 to <=5.1 implied moderate disease activity, >5.1 implied high disease activity, and DAS28-4 (CRP) <2.6 implied remission. DAS28-4 (CRP) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP in mg/L +1) + 0.014*PtGA in mm+ 0.96. Percentage of subjects with DAS remission (DAS28-4-CRP<2.6) were reported in this endpoint. NRI method was used to impute missing data. FAS-DB was analyzed.
    End point type
    Secondary
    End point timeframe
    Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    50.00
    55.64
        Week 48
    50.38
    54.51
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -5.63
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.12
         upper limit
    2.84
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -4.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.62
         upper limit
    4.36

    Secondary: Double Blind Phase: Percentage of Subjects With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects With Remission Assessed by CDAI <=2.8 at Weeks 36 and 48
    End point description
    CDAI was calculated from tender and swollen joints using 28 joint count, PtGA and PhyGA. PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity). CDAI total score ranged from 0 to 76, where higher scores indicated higher disease activity. CDAI score of <=10 indicated low disease activity and a score of <= 2.8 indicated remission. CDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm). NRI method was used to impute missing data. FAS-DB included all subjects who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase.
    End point type
    Secondary
    End point timeframe
    Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    23.48
    32.33
        Week 48
    28.41
    30.83
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -8.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -16.44
         upper limit
    -1.24
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -2.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.18
         upper limit
    5.35

    Secondary: Double Blind Phase: Percentage of Subjects With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects With Remission Assessed by SDAI <=3.3 at Weeks 36 and 48
    End point description
    SDAI was calculated from tender and swollen joints using 28 joint count, PtGA, PhyGA and CRP (in mg/dL). PtGA and PhyGA both were assessed on 0-10 cm VAS scale (VAS: scores ranging from 0 cm [very well] to 10 cm [worst]), where higher scores indicated greater affliction due to disease activity. SDAI total score ranged from 0 to 86, where higher scores indicated higher disease activity. SDAI score of <=11 indicates low disease activity and a score of <=3.3 indicates remission. SDAI = (28TJC) + (28SJC) + (PhyGA in cm) + (PtGA in cm) + (CRP in mg/dL). NRI method was used to impute missing data. FAS-DB included all subjects who received at least 1 dose of investigational drug during the OL phase, were randomized and received at least 1 dose of the randomized investigational drug regimen during DB phase.
    End point type
    Secondary
    End point timeframe
    Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    22.73
    31.58
        Week 48
    28.79
    31.95
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -8.85
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -16.38
         upper limit
    -1.31
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -3.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.99
         upper limit
    4.65

    Secondary: Double Blind Phase: Percentage of Subjects Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects Achieving an American College of Rheumatology 20 Percent (%) (ACR20) Response at Weeks 36 and 48
    End point description
    Subjects with 20% improvement in tender and swollen joint counts and 20% improvement in at least 3 of the 5 measures: PtGA, PhyGA, subject’s assessment of arthritis pain, HAQ-DI and CRP. PtGA: subject assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged subjects’ pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Subject’s assessment of arthritis pain: subject assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1). NRI method was used to impute missing data. FAS-DB was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    73.86
    80.83
        Week 48
    73.11
    79.70
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -6.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.06
         upper limit
    0.14
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -6.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.8
         upper limit
    0.61

    Secondary: Double Blind Phase: Percentage of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response at Week 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects Achieving an American College of Rheumatology 50% (ACR50) Response at Week 36 and 48
    End point description
    Subjects with 50% improvement in tender and swollen joint counts and 50% improvement in at least 3 of the 5 measures: PtGA, PhyGA, subject’s assessment of arthritis pain, HAQ-DI and CRP. PtGA: subject assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged subjects’ pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Subject’s assessment of arthritis pain: subject assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score = more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1). NRI method was used to impute missing data. FAS-DB was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    53.79
    66.54
        Week 48
    55.30
    67.29
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -12.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -21.01
         upper limit
    -4.48
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -11.99
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -20.22
         upper limit
    -3.75

    Secondary: Double Blind Phase: Percentage of Subjects Achieving an American College of Rheumatology 70% (ACR70) Response at Week 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects Achieving an American College of Rheumatology 70% (ACR70) Response at Week 36 and 48
    End point description
    Subjects with 70% improvement in tender and swollen joint counts and 70% improvement in at least 3 of the 5 measures: PtGA, PhyGA, subject’s assessment of arthritis pain, health assessment questionnaire-disability index (HAQ-DI) and CRP. PtGA: subject assessed health on VAS, 0 mm (very well) to 100 mm (worst health condition), higher scores = worse condition. PhyGA: physician judged subjects’ pain on VAS, 0 (no pain) to 100 mm (extreme pain), higher scores = more pain. Subject’s assessment of arthritis pain: subject assessed pain on VAS, 0 mm (no pain) to 100 mm (most severe pain), higher score=more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability. The improvement was relative to baseline (Day 1). NRI method was used to impute missing data. FAS-DB was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    35.61
    40.98
        Week 48
    37.88
    42.86
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -5.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.63
         upper limit
    2.89
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -4.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.32
         upper limit
    3.36

    Secondary: Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 36 and 48
    End point description
    HAQ-DI assesses the degree of difficulty a subject has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities. FAS-DB was analyzed. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: units on a scale
    least squares mean (standard error)
        Change at Week 36 (n =252, 259)
    0.10 ± 0.03
    0.01 ± 0.03
        Change at Week 48 (n =238, 246)
    0.01 ± 0.03
    0.00 ± 0.03
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological DMARD and baseline HAQ-DI.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.02
         upper limit
    0.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.04
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological DMARD and baseline HAQ-DI.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.06
         upper limit
    0.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.04

    Secondary: Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Week 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in the Short Form 36 (SF-36) Health Survey 8 Domain Scores at Week 36 and 48
    End point description
    SF-36 is a subject reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized to derive the 2 component scores (physical component scores [PCS], mental component scores [MCS]) ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition. FAS-DB was analyzed. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: units on a scale
    least squares mean (standard error)
        Change at Week 36:Physical Functioning(n=252, 259)
    -1.32 ± 0.50
    -0.88 ± 0.49
        Change at Week 36:Role Physical Score(n=252, 259)
    -1.69 ± 0.48
    -0.02 ± 0.47
        Change at Week 36: Social Functioning(n=252, 259)
    -0.98 ± 0.50
    -0.84 ± 0.49
        Change at Week 36: Bodily Pain Score (n=252, 259)
    -2.03 ± 0.53
    -0.58 ± 0.52
        Change at Week 36: Mental Health Score(n=251,259)
    -1.22 ± 0.51
    -0.32 ± 0.50
        Change at Week 36: Role Emotional Score(n=252,259)
    -1.80 ± 0.56
    -0.69 ± 0.55
        Change at Week 36: Vitality Score (n =251, 259)
    -1.30 ± 0.50
    -0.15 ± 0.50
        Change at Week 36: GH Perception Score (n=252,259)
    -0.98 ± 0.44
    -0.87 ± 0.43
        Change at Week 48:Physical Functioning(n=238,246)
    -0.46 ± 0.49
    -0.97 ± 0.48
        Change at Week 48: Role Physical Score(n=238,246)
    -0.88 ± 0.51
    -0.15 ± 0.50
        Change at Week 48: Social Functioning (n=238,246)
    -1.06 ± 0.53
    -0.55 ± 0.52
        Change at Week 48: Bodily Pain Score (n=238,246)
    -1.46 ± 0.54
    -0.71 ± 0.54
        Change at Week 48: Mental Health Score(n=238,246)
    -0.34 ± 0.54
    0.12 ± 0.54
        Change at Week 48:Role Emotional Score(n=238,246)
    -0.83 ± 0.54
    -0.36 ± 0.54
        Change at Week 48: Vitality Score (n =238, 246)
    -0.77 ± 0.52
    -0.25 ± 0.52
        Change at Week 48: GH Perception Score(n=238,246)
    -0.43 ± 0.45
    -1.05 ± 0.44
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Physical Functioning- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 physical component score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.79
         upper limit
    0.92
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.69
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Physical Functioning- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 physical component score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    0.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.82
         upper limit
    1.85
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.68
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Role Physical Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 role physical score score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -1.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.97
         upper limit
    -0.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Role Physical Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 role physical score score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.73
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.13
         upper limit
    0.66
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.66
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Social functioning- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 Social functioning score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.5
         upper limit
    1.21
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.69
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Social functioning- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 social functioning score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.95
         upper limit
    0.93
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.73
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Bodily Pain Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 bodily pain score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -1.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.9
         upper limit
    -0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.74
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Bodily Pain Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 bodily pain score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.23
         upper limit
    0.73
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.75
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Mental Health Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 mental health score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.29
         upper limit
    0.49
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.71
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Mental Health Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 mental health score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.94
         upper limit
    1.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.75
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Role Emotional Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 role emotional score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -1.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.64
         upper limit
    0.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.78
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Role Emotional Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 role emotional score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.95
         upper limit
    1.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.75
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Vitality Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 vitality score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -1.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.52
         upper limit
    0.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Vitality Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 vitality score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.94
         upper limit
    0.91
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.73
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: General Health Perception Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 general health perception score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.3
         upper limit
    1.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: General Health Perception Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 general health perception score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    0.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    1.83
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.62

    Secondary: Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Week 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in the SF-36 Health Survey Component Scores at Week 36 and 48
    End point description
    SF-36 is a subject reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health perception. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were summarized aggregated to derive the two 2 component scores PCS and MCS ranging from 0 (worst) to 100 (best), where higher PCS/MCS indicated good health condition. FAS-DB was analyzed. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: units on a scale
    least squares mean (standard error)
        Change at Week 36: PCS (n =251, 259)
    -1.42 ± 0.44
    -0.60 ± 0.43
        Change at Week 36:MCS (n =251, 259)
    -1.25 ± 0.48
    -0.43 ± 0.47
        Change at Week 48: PCS (n =238, 246)
    -0.83 ± 0.44
    -0.92 ± 0.43
        Change at Week 48: MCS (n =238, 246)
    -0.65 ± 0.51
    0.03 ± 0.50
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Physical Component Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 physical component score- as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.01
         upper limit
    0.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Physical Component Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 physical component score- as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.11
         upper limit
    1.29
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.61
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Mental Component Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 mental component score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.13
         upper limit
    0.49
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.67
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Mental Component Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a biological disease-modifying anti-rheumatic drug (DMARD), and baseline SF-36 mental component score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.68
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.06
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7

    Secondary: Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in the Work Productivity and Activity Impairment (WPAI) Scores at Week 36 and 48
    End point description
    WPAI is 6-question subject rated questionnaire to determine the impact of rheumatoid arthritis and yields 4 types of outcomes: absenteeism (work time missed), presenteeism (impairment while working), work productivity loss (overall work impairment), and daily activity (DA) impairment (activity impairment) for a period of 7 days prior to a visit. These 4 outcomes are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity. FAS-DB was analyzed. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage impairment
    least squares mean (standard error)
        Change at Week 36: Absenteeism (n =90, 104)
    -1.39 ± 1.79
    -3.00 ± 1.69
        Change at Week 36: DA impairment (n =252, 256)
    4.00 ± 1.35
    0.81 ± 1.34
        Change at Week 36: Presenteeism (n =96, 104)
    3.68 ± 2.20
    0.67 ± 2.07
        Change at Week 36:Work productivity loss(n=90,101)
    3.03 ± 2.57
    0.19 ± 2.41
        Change at Week 48: Absenteeism (n =89, 101)
    -2.21 ± 1.70
    -1.69 ± 1.61
        Change at Week 48: DA impairment (n =238, 243)
    2.86 ± 1.47
    1.25 ± 1.46
        Change at Week 48: Presenteeism (n =93, 101)
    2.82 ± 2.78
    3.72 ± 2.61
        Change at Week 48:Work productivity loss(n=89,98)
    2.98 ± 3.09
    5.45 ± 2.91
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Absenteeism Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI absenteeism score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    1.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.14
         upper limit
    6.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.41
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Absenteeism Score- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI absenteeism score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.01
         upper limit
    3.99
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.28
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Daily activity impairment- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI daily activity impairment score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    3.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.51
         upper limit
    6.89
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.88
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Daily activity impairment- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI daily activity impairment score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.41
         upper limit
    5.61
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.04
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Presenteeism- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI presenteeism score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    3.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.84
         upper limit
    8.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.97
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Presenteeism- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI presenteeism score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.34
         upper limit
    6.54
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.77
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Work productivity loss- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI work productivity loss score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    2.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.97
         upper limit
    9.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.45
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Work productivity loss- Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline WPAI work productivity loss score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -2.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.72
         upper limit
    5.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.19

    Secondary: Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Week 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Week 36 and 48
    End point description
    EQ-5D was a subject completed instrument designed to assess impact on quality of life in terms of a single utility score in 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. 3 possible answers for mobility: 1=no problem in walking, 2=moderate problems in walking, 3= confined to bed; self-care: 1=no problem, 2=moderate problems, 3= unable to wash/dress; usual activities: 1=no problem, 2=moderate problems, 3= unable to do usual activities; pain and discomfort: 1=no pain or discomfort, 2=moderate pain or discomfort, 3= extreme pain or discomfort; anxiety and depression: 1=not anxious or depressed, 2=moderately anxious or depressed, 3= extremely anxious or depressed. The 5-dimensional systems are converted into a single index utility score between 0 and 1, where higher score indicated a better health state. FAS-DB population was analyzed. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: units on a scale
    least squares mean (standard error)
        Change at Week 36 (n =251, 258)
    -0.05 ± 0.01
    -0.01 ± 0.01
        Change at Week 48 (n =237, 245)
    -0.02 ± 0.01
    0.00 ± 0.01
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline EQ-5D score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.07
         upper limit
    -0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.02
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline EQ-5D score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.06
         upper limit
    0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.02

    Secondary: Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)- Fatigue Scale Scores at Week 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Change From Randomization in the Functional Assessment of Chronic Illness Therapy (FACIT)- Fatigue Scale Scores at Week 36 and 48
    End point description
    The FACIT-Fatigue scale was a subject completed questionnaire consisted of 13 items that assessed fatigue. Each item was scored on a scale of 0 (maximum fatigue) to 4 (no fatigue), higher scores indicate less fatigue. Total FACIT-fatigue score was obtained by addition of scores from 13 items, giving a possible overall range from 0 (maximum fatigue) to 52 (no fatigue). Higher FACIT-fatigue scores indicated lower level of fatigue, better subject status. FAS-DB population was analyzed. Here, ‘n’ = Subjects evaluable for this endpoint at specified time points.
    End point type
    Secondary
    End point timeframe
    Randomization (last non-missing measurement on or prior to the first dosing date in DB phase at Week 24), Week 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: units on a scale
    least squares mean (standard error)
        Change at Week 36 (n =252, 258)
    -0.99 ± 0.43
    -0.80 ± 0.43
        Change at Week 48 (n =237, 245)
    -0.34 ± 0.46
    -0.52 ± 0.45
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 36: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline FACIT - fatigue scale score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    -0.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.37
         upper limit
    1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Change at Week 48: Linear MMRM was used that included the fixed effects of treatment, visit, treatment-by-visit interaction, prior use of a bDMARD, and baseline FACIT - fatigue scale score as a covariate.
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS Mean Difference
    Point estimate
    0.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.07
         upper limit
    1.44
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.64

    Secondary: Double Blind Phase: Percentage of Subjects Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48

    Close Top of page
    End point title
    Double Blind Phase: Percentage of Subjects Achieving an Improvement of at Least 0.22 Units in HAQ-DI at Weeks 36 and 48
    End point description
    HAQ-DI assesses the degree of difficulty a subject has experienced during the past week in 8 domains of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities.. There were total of 30 items distributed in these 8 domains. Each item was scored on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities. Percentage of subjects with an improvement of at least 0.22 units in HAQ scores from baseline (Day 1) to Week 36 and 48 were reported in this endpoint. NRI method was used to impute missing data. FAS-DB population was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 36 and 48
    End point values
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    264
    266
    Units: percentage of subjects
    number (not applicable)
        Week 36
    67.05
    77.07
        Week 48
    68.56
    75.19
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 36
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -10.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.61
         upper limit
    -2.42
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.87
    Statistical analysis title
    Tofacitinib + MTX Placebo Vs Tofacitinib + MTX
    Statistical analysis description
    Week 48
    Comparison groups
    Double Blind: Tofacitinib 11 mg + Methotrexate Placebo v Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects included in analysis
    530
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Difference in percentage of subjects
    Point estimate
    -6.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.26
         upper limit
    1
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.89

    Other pre-specified: Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious AEs

    Close Top of page
    End point title
    Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious AEs
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 52 (up to 28 days after last dose) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs. Overall study safety analysis set included all subjects who received at least one dose of study drug during the study.
    End point type
    Other pre-specified
    End point timeframe
    For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 52 (up to 28 days after last dose)
    End point values
    Open Label: Tofacitinib 11 mg + Methotrexate Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    694
    264
    266
    Units: subjects
        AEs|
    362
    107
    109
        SAEs|
    20
    10
    5
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects With Abnormal Laboratory Parameters

    Close Top of page
    End point title
    Number of Subjects With Abnormal Laboratory Parameters
    End point description
    Hemoglobin (Hb),Hematocrit,Erythrocytes:<0.8*LLN; Ery. mean corpuscular volume <0.9*LLN, >1.1*ULN;Platelets:<0.5*LLN,>1.75*ULN;WBCs:<0.6*LLN,>1.5*ULN; Lymphocytes/WBCs, Neutrophils/WBCs:<0.8*LLN,>1.2x ULN;Basophils/WBCs, Eosinophils/WBCs,Monocytes, Monocytes/WBCs: >1.2*ULN;Prothrombin Time, Prothrombin Intl. Normalized Ratio:>1.1*ULN; ESR:>1.5*ULN; Bilirubin,Direct Bilirubin,Indirect Bilirubin: >1.5*ULN; Aspartate Aminotransferase,Alanine Aminotransferase,Gamma Glutamyl Transferase,Alkaline Phosphatase:>3.0*ULN; Protein,Albumin: <0.8*LLN, >1.2*ULN; Blood Urea Nitrogen, Creatinine,Triglycerides: >1.3*ULN;HDL Cholesterol:<0.8*LLN;Sodium <0.95*LLN, >1.05*ULN;Potassium,Chloride, Calcium, Bicarbonate: <0.9*LLN, >1.1*ULN; Glucose: <0.6*LLN, >1.5*ULN;Creatine Kinase: >2.0*ULN; Cholesterol:>1.3*ULN;Specific Gravity:<1.003;pH:<4.5;urine glucose,Ketones,urine protein,urine Hb,WBCs Esterase:>=1.Overall safety analysis set.Overall number of subjects analyzed=subjects evaluable for this endpoint.
    End point type
    Other pre-specified
    End point timeframe
    For OL Phase: Baseline up to Week 24; For DB Phase: Week 24 up to Week 48
    End point values
    Open Label: Tofacitinib 11 mg + Methotrexate Double Blind: Tofacitinib 11 mg + Methotrexate Placebo Double Blind: Tofacitinib 11 mg + Methotrexate
    Number of subjects analysed
    688
    263
    263
    Units: subjects
    682
    263
    263
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Baseline (Day 1) up to Week 52
    Adverse event reporting additional description
    Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 subject and as non-serious in another subject or 1 subject may have experienced both serious and non-serious event during study. AEs were evaluated for subjects with at least 1 dose of the study drug during the study.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Open Label: Tofacitinib 11 mg + Methotrexate
    Reporting group description
    Subjects with moderate to severe rheumatoid arthritis (RA) and who were insufficiently responding to their stable dose of methotrexate treatment previous to enrollment in this study, received Tofacitinib modified release (MR) 11 milligram (mg) tablet once daily (QD) with methotrexate at their previous stable dose for 24 weeks in open label phase (OL).

    Reporting group title
    Double Blind: Tofacitinib 11mg + Methotrexate
    Reporting group description
    Subjects with LDA at the end of open label phase received Tofacitinib MR 11 mg tablet once daily with blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.

    Reporting group title
    Double Blind: Tofacitinib + Methotrexate Placebo
    Reporting group description
    Subjects with low disease activity (LDA) at the end of open label phase were randomized to receive Tofacitinib MR 11 mg tablet once daily with matching placebo to blinded methotrexate at their previously stabilized dose for 24 weeks in double blind phase.

    Serious adverse events
    Open Label: Tofacitinib 11 mg + Methotrexate Double Blind: Tofacitinib 11mg + Methotrexate Double Blind: Tofacitinib + Methotrexate Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 694 (2.88%)
    5 / 266 (1.88%)
    10 / 264 (3.79%)
         number of deaths (all causes)
    0
    2
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adrenal adenoma
         subjects affected / exposed
    0 / 694 (0.00%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glioblastoma
         subjects affected / exposed
    0 / 694 (0.00%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Prostate cancer
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Thyroid cancer metastatic
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Femur fracture
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 694 (0.00%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Patella fracture
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Investigations
    Blood pressure increased
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Angina unstable
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Atrial fibrillation
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Asthma
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 694 (0.00%)
    2 / 266 (0.75%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Interstitial lung disease
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Nervous system disorders
    Nerve root compression
         subjects affected / exposed
    0 / 694 (0.00%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Umbilical hernia
         subjects affected / exposed
    0 / 694 (0.00%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Pancreatitis acute
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Peritoneal disorder
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    0 / 694 (0.00%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Gallbladder disorder
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Musculoskeletal and connective tissue disorders
    Mobility decreased
         subjects affected / exposed
    0 / 694 (0.00%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 694 (0.00%)
    1 / 266 (0.38%)
    0 / 264 (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
    Dehydration
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Encephalitis viral
         subjects affected / exposed
    0 / 694 (0.00%)
    1 / 266 (0.38%)
    0 / 264 (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
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 694 (0.00%)
    1 / 266 (0.38%)
    0 / 264 (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
    Osteomyelitis
         subjects affected / exposed
    0 / 694 (0.00%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 694 (0.43%)
    0 / 266 (0.00%)
    1 / 264 (0.38%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Respiratory tract infection
         subjects affected / exposed
    1 / 694 (0.14%)
    0 / 266 (0.00%)
    0 / 264 (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
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    Open Label: Tofacitinib 11 mg + Methotrexate Double Blind: Tofacitinib 11mg + Methotrexate Double Blind: Tofacitinib + Methotrexate Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    158 / 694 (22.77%)
    31 / 266 (11.65%)
    24 / 264 (9.09%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    17 / 694 (2.45%)
    0 / 266 (0.00%)
    0 / 264 (0.00%)
         occurrences all number
    18
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    16 / 694 (2.31%)
    10 / 266 (3.76%)
    5 / 264 (1.89%)
         occurrences all number
    20
    11
    6
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 694 (0.00%)
    6 / 266 (2.26%)
    5 / 264 (1.89%)
         occurrences all number
    0
    6
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    17 / 694 (2.45%)
    0 / 266 (0.00%)
    0 / 264 (0.00%)
         occurrences all number
    19
    0
    0
    Dizziness
         subjects affected / exposed
    15 / 694 (2.16%)
    0 / 266 (0.00%)
    0 / 264 (0.00%)
         occurrences all number
    15
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    16 / 694 (2.31%)
    0 / 266 (0.00%)
    0 / 264 (0.00%)
         occurrences all number
    17
    0
    0
    Nausea
         subjects affected / exposed
    20 / 694 (2.88%)
    0 / 266 (0.00%)
    0 / 264 (0.00%)
         occurrences all number
    23
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 694 (0.00%)
    2 / 266 (0.75%)
    7 / 264 (2.65%)
         occurrences all number
    0
    2
    7
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 694 (0.00%)
    7 / 266 (2.63%)
    3 / 264 (1.14%)
         occurrences all number
    0
    8
    3
    Nasopharyngitis
         subjects affected / exposed
    35 / 694 (5.04%)
    7 / 266 (2.63%)
    5 / 264 (1.89%)
         occurrences all number
    40
    7
    6
    Upper respiratory tract infection
         subjects affected / exposed
    33 / 694 (4.76%)
    6 / 266 (2.26%)
    4 / 264 (1.52%)
         occurrences all number
    41
    6
    4
    Urinary tract infection
         subjects affected / exposed
    19 / 694 (2.74%)
    0 / 266 (0.00%)
    0 / 264 (0.00%)
         occurrences all number
    20
    0
    0

    More information

    Close Top of page

    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
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA