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    Clinical Trial Results:
    A Phase 3 Randomized, Double Blind Study Assessing the Efficacy and Safety of PF-06410293 and Adalimumab in Combination With Methotrexate in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate

    Summary
    EudraCT number
    2014-000352-29
    Trial protocol
    CZ   EE   LT   HU   GB   DE   ES   FR   BG   HR  
    Global end of trial date
    06 Dec 2017

    Results information
    Results version number
    v3(current)
    This version publication date
    17 Mar 2019
    First version publication date
    13 Sep 2017
    Other versions
    v1 , v2
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    B5381002
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02480153
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +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
    26 Jul 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Dec 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare the treatment efficacy between adalimumab-Pfizer (PF-06410293) and adalimumab-EU (adalimumab sourced from the European Union) in subjects with moderately to severely active rheumatoid arthritis who were treated with adalimumab in combination with methotrexate.
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.
    Background therapy
    Subjects continued their stable background regimen of oral or intramuscular methotrexate (10 to 25 mg/week, with the exception of 6 to 25 mg/week in geographic regions where 6 mg/week was a recommended initial dose by local guidance or standard of care) throughout the study.
    Evidence for comparator
    This study was designed to compare the treatment efficacy between PF-06410293 and adalimumab-EU; therefore, adalimumab-EU was used as the comparator.
    Actual start date of recruitment
    25 Jun 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    4 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    South Africa: 15
    Country: Number of subjects enrolled
    Spain: 21
    Country: Number of subjects enrolled
    Taiwan: 5
    Country: Number of subjects enrolled
    Ukraine: 66
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    United States: 75
    Country: Number of subjects enrolled
    Australia: 5
    Country: Number of subjects enrolled
    Brazil: 2
    Country: Number of subjects enrolled
    Bulgaria: 37
    Country: Number of subjects enrolled
    Colombia: 3
    Country: Number of subjects enrolled
    Czech Republic: 31
    Country: Number of subjects enrolled
    Estonia: 3
    Country: Number of subjects enrolled
    Georgia: 33
    Country: Number of subjects enrolled
    Germany: 13
    Country: Number of subjects enrolled
    Hungary: 14
    Country: Number of subjects enrolled
    Japan: 17
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    Lithuania: 30
    Country: Number of subjects enrolled
    Mexico: 10
    Country: Number of subjects enrolled
    New Zealand: 4
    Country: Number of subjects enrolled
    Peru: 24
    Country: Number of subjects enrolled
    Poland: 87
    Country: Number of subjects enrolled
    Russian Federation: 56
    Country: Number of subjects enrolled
    Serbia: 35
    Worldwide total number of subjects
    597
    EEA total number of subjects
    241
    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)
    480
    From 65 to 84 years
    117
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 1231 potential subjects were screened after signing an informed consent form, of whom 597 subjects were randomized to receive study treatment.

    Period 1
    Period 1 title
    Period 1: First Dose to Week 26 Pre-dose
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Investigator, Carer, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    PF-06410293
    Arm description
    Period 1 (first dose to Week 26 predose assessments): subjects were blindly randomized in a 1:1 ratio to receive PF-06410293 (a biosimilar to Humira) or adalimumab-EU (Humira from European Union) 40 mg every 2 weeks by subcutaneous injection.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-06410293
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PF-06410293 40 mg was administered every other week by subcutaneous injection in Period 1.

    Arm title
    Adalimumab-EU
    Arm description
    Period 1 (first dose to Week 26 predose assessments): subjects were blindly randomized in a 1:1 ratio to receive PF-06410293 (a biosimilar to Humira) or adalimumab-EU (Humira from European Union) 40 mg every 2 weeks by subcutaneous injection.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab-EU
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Adalimumab-EU 40 mg was administered every other week by subcutaneous injection in Period 1.

    Number of subjects in period 1
    PF-06410293 Adalimumab-EU
    Started
    297
    300
    Received treatment
    297
    299
    Completed
    293
    284
    Not completed
    4
    16
         Non-compliance with study treatment
    -
    1
         Adverse event, serious fatal
    -
    1
         Adverse event, non-fatal
    1
    2
         Unspecified
    -
    1
         Consent withdrawn by subject
    3
    8
         Insufficient clinical response
    -
    1
         Lost to follow-up
    -
    2
    Period 2
    Period 2 title
    Period 2: Week 26 to Week 52 Pre-dose
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    PF-06410293/PF-06410293
    Arm description
    Period 2 began with the blinded study drug dosing at Week 26 and ended with the completion of Week 52 pre-dose assessments. All subjects initially randomized into PF-06410293 arm in Period 1 continued to receive PF-06410293 40 mg every 2 weeks by subcutaneous injection in Period 2.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-06410293
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PF-06410293 40 mg was administered every other week by subcutaneous injection.

    Arm title
    Adalimumab-EU/Adalimumab-EU
    Arm description
    Period 2 began with the blinded study drug dosing at Week 26 and ended with the completion of Week 52 pre-dose assessments. A second randomization was blindly performed prior to dosing at Week 26, when subjects initially randomized to adalimumab-EU were re-randomized in a 1:1 ratio, with 50% of the subjects switching to PF-06410293 and the other 50% remaining in the adalimumab-EU arm.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab-EU
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Adalimumab-EU 40 mg was administered every other week by subcutaneous injection.

    Arm title
    Adalimumab-EU/PF-06410293
    Arm description
    Period 2 began with the blinded study drug dosing at Week 26 and ended with the completion of Week 52 pre-dose assessments. A second randomization was blindly performed prior to dosing at Week 26, when subjects initially randomized to adalimumab-EU were re-randomized in a 1:1 ratio, with 50% of the subjects switching to PF-06410293 and the other 50% remaining in the adalimumab-EU arm.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-06410293
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PF-06410293 40 mg was administered every other week by subcutaneous injection.

    Number of subjects in period 2 [1]
    PF-06410293/PF-06410293 Adalimumab-EU/Adalimumab-EU Adalimumab-EU/PF-06410293
    Started
    283
    135
    134
    Received treatment
    283
    135
    133
    Completed
    263
    122
    127
    Not completed
    20
    13
    7
         Non-compliance with study treatment
    -
    1
    -
         Adverse event, non-fatal
    6
    7
    3
         Unspecified
    2
    -
    -
         Consent withdrawn by subject
    8
    3
    1
         Insufficient clinical response
    4
    1
    3
         Lost to follow-up
    -
    1
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: A second randomization was blindly performed prior to dosing at Week 26, when subjects initially randomized to adalimumab-EU were re-randomized in a 1:1 ratio, with 50% of the subjects switching to PF-06410293 and the other 50% remaining in the adalimumab-EU arm.
    Period 3
    Period 3 title
    Period 3: Week 52 dosing to Week 78
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    PF-06410293/PF-06410293/PF-06410293
    Arm description
    Subjects in this reporting group were initially randomized to the PF-06410293 group in Period 1, and received PF-06410293 (a potential biosimilar to Humira) 40 mg every 2 weeks by subcutaneous injection in all the 3 treatment periods. Period 3 began with open-label PF-06410293 dosing at Week 52 and ended with end of treatment visit at Week 78.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-06410293
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PF-06410293 40 mg was administered every other week by subcutaneous injection in Period 3.

    Arm title
    Adalimumab-EU/adalimumab-EU/PF-06410293
    Arm description
    Subjects initially randomized to adalimumab-EU in Period 1 were re-randomized in a 1:1 ratio in Period 2, with 50% of the subjects switching to PF-06410293 and the other 50% remaining in the adalimumab-EU arm. In Period 3, all the remaining subjects on adalimumab-EU were switched to open-label PF-06410293. Period 3 began with open-label PF-06410293 dosing at Week 52 and ended with end of treatment visit at Week 78.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-06410293
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PF-06410293 40 mg was administered every other week by subcutaneous injection in Period 3.

    Arm title
    Adalimumab-EU/PF-06410293/PF-06410293
    Arm description
    Subjects initially randomized to adalimumab-EU in Period 1 were re-randomized in a 1:1 ratio in Period 2, with 50% of the subjects switching to PF-06410293 and the other 50% remaining in the adalimumab-EU arm. In Period 3, all the remaining subjects on adalimumab-EU were switched to open-label PF-06410293. Period 3 began with open-label PF-06410293 dosing at Week 52 and ended with end of treatment visit at Week 78.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-06410293
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PF-06410293 40 mg was administered every other week by subcutaneous injection in Period 3.

    Number of subjects in period 3 [2]
    PF-06410293/PF-06410293/PF-06410293 Adalimumab-EU/adalimumab-EU/PF-06410293 Adalimumab-EU/PF-06410293/PF-06410293
    Started
    259
    121
    127
    Received treatment
    258
    120
    127
    Completed
    252
    118
    123
    Not completed
    7
    3
    4
         Adverse event, serious fatal
    -
    1
    -
         Adverse event, non-fatal
    -
    -
    1
         Unspecified
    -
    -
    1
         Consent withdrawn by subject
    3
    2
    1
         Lost to follow-up
    4
    -
    1
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Period 3 began with open-label PF-06410293 dosing at Week 52 and ended with end of treatment visit at Week 78. Subjects were followed up for 16 weeks after the last dose of study drug (up to Week 92).

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PF-06410293
    Reporting group description
    Period 1 (first dose to Week 26 predose assessments): subjects were blindly randomized in a 1:1 ratio to receive PF-06410293 (a biosimilar to Humira) or adalimumab-EU (Humira from European Union) 40 mg every 2 weeks by subcutaneous injection.

    Reporting group title
    Adalimumab-EU
    Reporting group description
    Period 1 (first dose to Week 26 predose assessments): subjects were blindly randomized in a 1:1 ratio to receive PF-06410293 (a biosimilar to Humira) or adalimumab-EU (Humira from European Union) 40 mg every 2 weeks by subcutaneous injection.

    Reporting group values
    PF-06410293 Adalimumab-EU Total
    Number of subjects
    297 300 597
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    245 235 480
        From 65-84 years
    52 65 117
        85 years and over
    0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    51.5 ± 13.6 53.5 ± 12.9 -
    Sex: Female, Male
    Units: Subjects
        Female
    241 229 470
        Male
    56 71 127
    Race/Ethnicity, Customized
    Units: Subjects
        White
    261 256 517
        Black
    6 9 15
        Asian
    16 17 33
        Other
    14 18 32
    Subject analysis sets

    Subject analysis set title
    Period 1: PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the PF-06410293 group in Period 1, where PF-06410293 40 mg was administered every other week by subcutaneous injection.

    Subject analysis set title
    Period 1: Adalimumab-EU
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1, where adalimumab-EU 40 mg was administered every other week by subcutaneous injection.

    Subject analysis set title
    Period 2: PF-06410293/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the PF-06410293 group in Period 1 and continued to receive PF-06410293 in Period 2. PF-06410293 40 mg was administered every other week by subcutaneous injection in both periods.

    Subject analysis set title
    Period 2: Adalimumab-EU/Adalimumab-EU
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1 and remained in the adalimumab-EU group in Period 2. Adalimumab-EU 40 mg was administered every other week by subcutaneous injection in both periods.

    Subject analysis set title
    Period 2: Adalimumab-EU/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1 and switched to PF-06410293 in Period 2. Study drug 40 mg was administered every other week by subcutaneous injection in both periods.

    Subject analysis set title
    Period 3: PF-06410293/PF-06410293/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the PF-06410293 group in Period 1 and continued to receive PF-06410293 in Period 2 and Period 3. PF-06410293 40 mg was administered every other week by subcutaneous injection in all 3 periods.

    Subject analysis set title
    Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1, remained in the adalimumab-EU group in Period 2 and received PF-06410293 in Period 3. Study drug 40 mg was administered every other week by subcutaneous injection in all 3 periods.

    Subject analysis set title
    Period 3: Adalimumab-EU/PF-06410293/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1 and switched to PF-06410293 from Period 2 and continued on PF-06410293 in Period 3. Study drug 40 mg was administered every other week by subcutaneous injection in all 3 periods.

    Subject analysis set title
    Period 3 Total
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who entered Period 3, where PF-06410293 40 mg was administered every other week by subcutaneous injection.

    Subject analysis set title
    Sub-study: PF-06410293 PFP
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received 6 consecutive bi-weekly PF-06410293 doses over a period of 10 weeks (Week 56 to Week 66) using the PFP device provided by the sponsor. The first, third and sixth injections were administered at the study site under the supervision of the investigator or a designated observer. All other injections (the second, fourth and fifth) were administered at home.

    Subject analysis sets values
    Period 1: PF-06410293 Period 1: Adalimumab-EU Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293 Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total Sub-study: PF-06410293 PFP
    Number of subjects
    297
    300
    283
    135
    134
    259
    121
    127
    507
    50
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Adults (18-64 years)
    245
    235
    234
    106
    103
    215
    99
    98
    412
    36
        From 65-84 years
    52
    65
    49
    29
    31
    44
    22
    29
    95
    14
        85 years and over
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    51.5 ± 13.6
    53.5 ± 12.9
    51.3 ± 13.7
    53.6 ± 12.1
    53.4 ± 13.4
    51.1 ± 13.8
    53.1 ± 11.7
    53.1 ± 13.5
    52.1 ± 13.3
    54.9 ± 13.1
    Sex: Female, Male
    Units: Subjects
        Female
    241
    229
    229
    108
    95
    210
    98
    88
    396
    37
        Male
    56
    71
    54
    27
    39
    49
    23
    39
    111
    13
    Race/Ethnicity, Customized
    Units: Subjects
        White
    261
    256
    250
    113
    116
    230
    100
    109
    439
    46
        Black
    6
    9
    6
    7
    2
    5
    7
    2
    14
    4
        Asian
    16
    17
    14
    8
    6
    11
    7
    6
    24
    0
        Other
    14
    18
    13
    7
    10
    13
    7
    10
    30
    0

    End points

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    End points reporting groups
    Reporting group title
    PF-06410293
    Reporting group description
    Period 1 (first dose to Week 26 predose assessments): subjects were blindly randomized in a 1:1 ratio to receive PF-06410293 (a biosimilar to Humira) or adalimumab-EU (Humira from European Union) 40 mg every 2 weeks by subcutaneous injection.

    Reporting group title
    Adalimumab-EU
    Reporting group description
    Period 1 (first dose to Week 26 predose assessments): subjects were blindly randomized in a 1:1 ratio to receive PF-06410293 (a biosimilar to Humira) or adalimumab-EU (Humira from European Union) 40 mg every 2 weeks by subcutaneous injection.
    Reporting group title
    PF-06410293/PF-06410293
    Reporting group description
    Period 2 began with the blinded study drug dosing at Week 26 and ended with the completion of Week 52 pre-dose assessments. All subjects initially randomized into PF-06410293 arm in Period 1 continued to receive PF-06410293 40 mg every 2 weeks by subcutaneous injection in Period 2.

    Reporting group title
    Adalimumab-EU/Adalimumab-EU
    Reporting group description
    Period 2 began with the blinded study drug dosing at Week 26 and ended with the completion of Week 52 pre-dose assessments. A second randomization was blindly performed prior to dosing at Week 26, when subjects initially randomized to adalimumab-EU were re-randomized in a 1:1 ratio, with 50% of the subjects switching to PF-06410293 and the other 50% remaining in the adalimumab-EU arm.

    Reporting group title
    Adalimumab-EU/PF-06410293
    Reporting group description
    Period 2 began with the blinded study drug dosing at Week 26 and ended with the completion of Week 52 pre-dose assessments. A second randomization was blindly performed prior to dosing at Week 26, when subjects initially randomized to adalimumab-EU were re-randomized in a 1:1 ratio, with 50% of the subjects switching to PF-06410293 and the other 50% remaining in the adalimumab-EU arm.
    Reporting group title
    PF-06410293/PF-06410293/PF-06410293
    Reporting group description
    Subjects in this reporting group were initially randomized to the PF-06410293 group in Period 1, and received PF-06410293 (a potential biosimilar to Humira) 40 mg every 2 weeks by subcutaneous injection in all the 3 treatment periods. Period 3 began with open-label PF-06410293 dosing at Week 52 and ended with end of treatment visit at Week 78.

    Reporting group title
    Adalimumab-EU/adalimumab-EU/PF-06410293
    Reporting group description
    Subjects initially randomized to adalimumab-EU in Period 1 were re-randomized in a 1:1 ratio in Period 2, with 50% of the subjects switching to PF-06410293 and the other 50% remaining in the adalimumab-EU arm. In Period 3, all the remaining subjects on adalimumab-EU were switched to open-label PF-06410293. Period 3 began with open-label PF-06410293 dosing at Week 52 and ended with end of treatment visit at Week 78.

    Reporting group title
    Adalimumab-EU/PF-06410293/PF-06410293
    Reporting group description
    Subjects initially randomized to adalimumab-EU in Period 1 were re-randomized in a 1:1 ratio in Period 2, with 50% of the subjects switching to PF-06410293 and the other 50% remaining in the adalimumab-EU arm. In Period 3, all the remaining subjects on adalimumab-EU were switched to open-label PF-06410293. Period 3 began with open-label PF-06410293 dosing at Week 52 and ended with end of treatment visit at Week 78.

    Subject analysis set title
    Period 1: PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the PF-06410293 group in Period 1, where PF-06410293 40 mg was administered every other week by subcutaneous injection.

    Subject analysis set title
    Period 1: Adalimumab-EU
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1, where adalimumab-EU 40 mg was administered every other week by subcutaneous injection.

    Subject analysis set title
    Period 2: PF-06410293/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the PF-06410293 group in Period 1 and continued to receive PF-06410293 in Period 2. PF-06410293 40 mg was administered every other week by subcutaneous injection in both periods.

    Subject analysis set title
    Period 2: Adalimumab-EU/Adalimumab-EU
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1 and remained in the adalimumab-EU group in Period 2. Adalimumab-EU 40 mg was administered every other week by subcutaneous injection in both periods.

    Subject analysis set title
    Period 2: Adalimumab-EU/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1 and switched to PF-06410293 in Period 2. Study drug 40 mg was administered every other week by subcutaneous injection in both periods.

    Subject analysis set title
    Period 3: PF-06410293/PF-06410293/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the PF-06410293 group in Period 1 and continued to receive PF-06410293 in Period 2 and Period 3. PF-06410293 40 mg was administered every other week by subcutaneous injection in all 3 periods.

    Subject analysis set title
    Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1, remained in the adalimumab-EU group in Period 2 and received PF-06410293 in Period 3. Study drug 40 mg was administered every other week by subcutaneous injection in all 3 periods.

    Subject analysis set title
    Period 3: Adalimumab-EU/PF-06410293/PF-06410293
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1 and switched to PF-06410293 from Period 2 and continued on PF-06410293 in Period 3. Study drug 40 mg was administered every other week by subcutaneous injection in all 3 periods.

    Subject analysis set title
    Period 3 Total
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    This reporting group refers to the subjects who entered Period 3, where PF-06410293 40 mg was administered every other week by subcutaneous injection.

    Subject analysis set title
    Sub-study: PF-06410293 PFP
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received 6 consecutive bi-weekly PF-06410293 doses over a period of 10 weeks (Week 56 to Week 66) using the PFP device provided by the sponsor. The first, third and sixth injections were administered at the study site under the supervision of the investigator or a designated observer. All other injections (the second, fourth and fifth) were administered at home.

    Primary: Percentage of Subjects with an American College of Rheumatology 20% (ACR20) Response at Week 12: Period 1

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    End point title
    Percentage of Subjects with an American College of Rheumatology 20% (ACR20) Response at Week 12: Period 1
    End point description
    ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects who were randomized to study treatment.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: percentage of subjects
        number (not applicable)
    68.35
    71.33
    Statistical analysis title
    Percentage difference with 95% CI
    Comparison groups
    Period 1: PF-06410293 v Period 1: Adalimumab-EU
    Number of subjects included in analysis
    597
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [1]
    Method
    Parameter type
    Week 12 ACR20 response rate difference
    Point estimate
    -2.98
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.38
         upper limit
    4.44
    Notes
    [1] - Confidence interval (CIs) calculated by the score statistic method were used for the inference of the equivalence for ACR20 at Week 12. Therapeutic equivalence could be established if the 2-sided 95% CI fell within (-14%, 14%). Non-responder imputation was applied. Comparisons between treatments were computed as PF-06410293 versus Adalimumab-EU.
    Statistical analysis title
    Percentage difference with 90% CI
    Comparison groups
    Period 1: PF-06410293 v Period 1: Adalimumab-EU
    Number of subjects included in analysis
    597
    Analysis specification
    Pre-specified
    Analysis type
    equivalence [2]
    Method
    Parameter type
    Week 12 ACR20 response rate difference
    Point estimate
    -2.98
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -9.25
         upper limit
    3.28
    Notes
    [2] - Confidence interval (CIs) calculated by the score statistic method were used for the inference of the equivalence for ACR20 at Week 12. Therapeutic equivalence could be established if 2-sided 90% CI fell within (-12%, 15%). Non-responder imputation was applied. Comparisons between treatments were computed as PF-06410293 versus Adalimumab-EU.

    Secondary: Number of Subjects With an American College of Rheumatology 20% (ACR20) Response at Other Time Points Other Than Week 12: Period 1

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    End point title
    Number of Subjects With an American College of Rheumatology 20% (ACR20) Response at Other Time Points Other Than Week 12: Period 1
    End point description
    ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: subjects
        Week 2
    93
    96
        Week 4
    154
    157
        Week 6
    182
    179
        Week 8
    206
    204
        Week 18
    232
    221
        Week 26 (pre-dose)
    248
    234
    No statistical analyses for this end point

    Secondary: Number of Subjects With an American College of Rheumatology 20% (ACR20) Response: Period 2

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    End point title
    Number of Subjects With an American College of Rheumatology 20% (ACR20) Response: Period 2
    End point description
    ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: subjects
        Week 26
    245
    114
    116
        Week 30
    245
    111
    116
        Week 36
    236
    105
    118
        Week 44
    233
    106
    108
        Week 52 (pre-dose)
    234
    107
    113
    No statistical analyses for this end point

    Secondary: Number of Subjects With an American College of Rheumatology 20% (ACR20) Response: Period 3

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    End point title
    Number of Subjects With an American College of Rheumatology 20% (ACR20) Response: Period 3
    End point description
    ACR20 is a categorical variable indicating a 20% or greater improvement in tender and swollen joint counts and 20% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: subjects
        Week 52
    229
    106
    112
    447
        Week 56
    230
    105
    106
    441
        Week 66
    226
    103
    108
    437
        Week 76
    219
    95
    106
    420
        Week 78
    216
    102
    109
    427
    No statistical analyses for this end point

    Secondary: Number of Subjects With an American College of Rheumatology 50% (ACR50) Response: Period 1

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    End point title
    Number of Subjects With an American College of Rheumatology 50% (ACR50) Response: Period 1
    End point description
    ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: subjects
        Week 2
    25
    18
        Week 4
    53
    43
        Week 6
    82
    82
        Week 8
    101
    100
        Week 12
    118
    119
        Week 18
    134
    141
        Week 26 (pre-dose)
    177
    164
    No statistical analyses for this end point

    Secondary: Number of Subjects With an American College of Rheumatology 50% (ACR50) Response: Period 2

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    End point title
    Number of Subjects With an American College of Rheumatology 50% (ACR50) Response: Period 2
    End point description
    ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: subjects
        Week 26
    175
    76
    86
        Week 30
    169
    67
    82
        Week 36
    173
    70
    94
        Week 44
    182
    67
    87
        Week 52 (pre-dose)
    178
    75
    97
    No statistical analyses for this end point

    Secondary: Number of Subjects With an American College of Rheumatology 50% (ACR50) Response: Period 3

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    End point title
    Number of Subjects With an American College of Rheumatology 50% (ACR50) Response: Period 3
    End point description
    ACR50 is a categorical variable indicating a 50% or greater improvement in tender and swollen joint counts and 50% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: subjects
        Week 52
    177
    74
    96
    347
        Week 56
    175
    78
    94
    347
        Week 66
    177
    75
    92
    344
        Week 76
    179
    66
    90
    335
        Week 78
    185
    71
    90
    346
    No statistical analyses for this end point

    Secondary: Number of Subjects With an American College of Rheumatology 70% (ACR70) Response: Period 1

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    End point title
    Number of Subjects With an American College of Rheumatology 70% (ACR70) Response: Period 1
    End point description
    ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: subjects
        Week 2
    2
    6
        Week 4
    11
    11
        Week 6
    24
    26
        Week 8
    37
    35
        Week 12
    49
    57
        Week 18
    64
    66
        Week 26 (pre-dose)
    88
    93
    No statistical analyses for this end point

    Secondary: Number of Subjects With an American College of Rheumatology 70% (ACR70) Response: Period 2

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    End point title
    Number of Subjects With an American College of Rheumatology 70% (ACR70) Response: Period 2
    End point description
    ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: subjects
        Week 26
    88
    41
    52
        Week 30
    96
    41
    49
        Week 36
    102
    36
    59
        Week 44
    109
    44
    53
        Week 52 (pre-dose)
    103
    43
    59
    No statistical analyses for this end point

    Secondary: Number of Subjects With an American College of Rheumatology 70% (ACR70) Response: Period 3

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    End point title
    Number of Subjects With an American College of Rheumatology 70% (ACR70) Response: Period 3
    End point description
    ACR70 is a categorical variable indicating a 70% or greater improvement in tender and swollen joint counts and 70% or greater improvement in 3 of the 5 other ACR-core set measures: patient's assessment of arthritis pain (PAAP); patient's global assessment of arthritis (PGA); physician's global assessment of arthritis (PGAA); high sensitivity C-reactive protein (hs-CRP); and Health Assessment Questionnaire - Disability Index (HAQ-DI). The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: subjects
        Week 52
    103
    42
    58
    203
        Week 56
    101
    42
    59
    202
        Week 66
    112
    48
    60
    220
        Week 76
    118
    39
    63
    220
        Week 78
    128
    48
    69
    245
    No statistical analyses for this end point

    Secondary: Change From Baseline in Tender Joint Count: Period 1

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    End point title
    Change From Baseline in Tender Joint Count: Period 1
    End point description
    Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V). The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: joints
    arithmetic mean (standard deviation)
        Baseline
    24.3 ± 12.29
    26.7 ± 14.80
        Change at Week 2
    -7.5 ± 9.89
    -7.1 ± 9.14
        Change at Week 4
    -10.2 ± 10.59
    -10.7 ± 9.92
        Change at Week 6
    -12.8 ± 11.28
    -13.1 ± 11.93
        Change at Week 8
    -14.2 ± 11.37
    -15.2 ± 11.84
        Change at Week 12
    -15.4 ± 11.69
    -16.1 ± 12.65
        Change at Week 18
    -16.8 ± 11.42
    -17.3 ± 12.69
        Change at Week 26 (pre-dose)
    -18.4 ± 11.41
    -19.2 ± 12.52
    No statistical analyses for this end point

    Secondary: Change From Baseline in Tender Joint Count: Period 2

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    End point title
    Change From Baseline in Tender Joint Count: Period 2
    End point description
    Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V). The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: joints
    arithmetic mean (standard deviation)
        Baseline
    23.7 ± 11.87
    26.8 ± 14.72
    25.5 ± 15.00
        Change at Week 26
    -18.4 ± 11.34
    -20.1 ± 12.47
    -19.3 ± 11.99
        Change at Week 30
    -19.0 ± 11.85
    -19.5 ± 14.28
    -19.4 ± 12.22
        Change at Week 36
    -18.7 ± 12.01
    -20.1 ± 12.62
    -20.4 ± 12.56
        Change at Week 44
    -19.4 ± 12.01
    -21.5 ± 13.56
    -20.2 ± 12.94
        Change at Week 52 (pre-dose)
    -18.9 ± 11.49
    -21.0 ± 14.14
    -21.2 ± 12.95
    No statistical analyses for this end point

    Secondary: Change From Baseline in Tender Joint Count: Period 3

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    End point title
    Change From Baseline in Tender Joint Count: Period 3
    End point description
    Sixty-eight (68) joints were assessed by an independent blinded joint assessor to determine the number of joints that were considered tender. The 68 joints assessed were: upper body including temporomandibular, sternoclavicular, acromioclavicular; upper extremity including shoulder, elbow, wrist (radiocarpal, carpal and carpometacarpal considered as 1 unit), metacarpophalangeals (MCP I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (PIP II, III, IV, V), and distal interphalangeals (DIP II, III, IV, V); lower extremity including hip, knee, ankle, tarsus (subtalar, transverse tarsal and tarsometatarsal considered as 1 unit), metatarsophalangeals (MTP I, II, III, IV, V), great toe interphalangeal, proximal and distal interphalangeals combined (PIP and DIP II, III, IV, V). The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: joints
    arithmetic mean (standard deviation)
        Baseline
    23.8 ± 11.89
    26.5 ± 14.97
    25.4 ± 14.77
    24.9 ± 13.45
        Change at Week 52
    -19.3 ± 11.38
    -21.2 ± 14.13
    -21.2 ± 13.00
    -20.2 ± 12.50
        Change at Week 56
    -19.4 ± 11.27
    -21.1 ± 13.55
    -21.6 ± 13.43
    -20.4 ± 12.42
        Change at Week 66
    -19.5 ± 10.97
    -21.3 ± 12.83
    -21.6 ± 13.55
    -20.5 ± 12.12
        Change at Week 76
    -20.6 ± 11.75
    -22.0 ± 14.06
    -22.0 ± 14.00
    -21.3 ± 12.89
        Change at Week 78
    -20.5 ± 11.53
    -21.1 ± 13.23
    -22.1 ± 14.26
    -21.1 ± 12.67
    No statistical analyses for this end point

    Secondary: Change From Baseline in Swollen Joint Count: Period 1

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    End point title
    Change From Baseline in Swollen Joint Count: Period 1
    End point description
    Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints. The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: joints
    arithmetic mean (standard deviation)
        Baseline
    15.4 ± 7.81
    17.0 ± 9.86
        Change at Week 2
    -5.7 ± 6.31
    -6.1 ± 7.23
        Change at Week 4
    -7.7 ± 7.04
    -8.2 ± 8.38
        Change at Week 6
    -9.0 ± 7.37
    -9.7 ± 8.97
        Change at Week 8
    -9.8 ± 7.06
    -11.0 ± 8.50
        Change at Week 12
    -10.4 ± 7.38
    -11.8 ± 8.87
        Change at Week 18
    -11.3 ± 6.76
    -13.0 ± 9.45
        Change at Week 26 (pre-dose)
    -12.2 ± 7.18
    -13.6 ± 9.12
    No statistical analyses for this end point

    Secondary: Change From Baseline in Swollen Joint Count: Period 2

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    End point title
    Change From Baseline in Swollen Joint Count: Period 2
    End point description
    Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints. The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: joints
    arithmetic mean (standard deviation)
        Baseline
    15.1 ± 7.66
    17.1 ± 9.60
    17.0 ± 10.31
        Change at Week 26
    -12.2 ± 7.11
    -13.6 ± 8.15
    -14.3 ± 9.84
        Change at Week 30
    -12.3 ± 7.58
    -13.3 ± 9.31
    -14.3 ± 9.70
        Change at Week 36
    -12.4 ± 7.76
    -14.2 ± 8.74
    -14.6 ± 9.69
        Change at Week 44
    -12.8 ± 7.12
    -14.7 ± 8.87
    -14.8 ± 9.97
        Change at Week 52 (pre-dose)
    -12.6 ± 6.92
    -14.2 ± 8.29
    -15.2 ± 9.82
    No statistical analyses for this end point

    Secondary: Change From Baseline in Swollen Joint Count: Period 3

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    End point title
    Change From Baseline in Swollen Joint Count: Period 3
    End point description
    Sixty-six (66) joints were assessed for swelling, the same as those listed for tender joint count, excluding the right and left hip joints. The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: joints
    arithmetic mean (standard deviation)
        Baseline
    15.0 ± 7.59
    17.3 ± 9.77
    16.8 ± 10.07
    16.0 ± 8.85
        Change at Week 52
    -12.8 ± 6.87
    -14.4 ± 8.22
    -15.2 ± 9.75
    -13.7 ± 8.05
        Change at Week 56
    -12.9 ± 6.61
    -14.5 ± 8.65
    -14.9 ± 9.65
    -13.8 ± 8.00
        Change at Week 66
    -13.0 ± 7.09
    -14.9 ± 8.37
    -15.2 ± 9.92
    -14.0 ± 8.23
        Change at Week 76
    -13.3 ± 7.12
    -14.9 ± 8.86
    -15.1 ± 10.27
    -14.1 ± 8.44
        Change at Week 78
    -13.4 ± 7.25
    -15.0 ± 9.35
    -15.1 ± 10.24
    -14.2 ± 8.63
    No statistical analyses for this end point

    Secondary: Change From Baseline in Physician’s Global Assessment of Arthritis (PGAA): Period 1

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    End point title
    Change From Baseline in Physician’s Global Assessment of Arthritis (PGAA): Period 1
    End point description
    The investigator assessed how the subject’s overall arthritis appeared at the time of the visit. This was an evaluation based on the subject’s disease symptoms, functional capacity and physical examination, and independent of the subject’s reported assessments of PGA (patient’s global assessment of arthritis) and PAAP (patient’s assessment of arthritis pain). The investigator’s response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled “None” and the 100 mm end labeled “Extreme”. The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    65.0 ± 15.22
    66.7 ± 15.80
        Change at Week 2
    -20.7 ± 18.62
    -20.5 ± 18.87
        Change at Week 4
    -28.9 ± 20.24
    -29.0 ± 18.29
        Change at Week 6
    -32.6 ± 21.72
    -33.0 ± 19.87
        Change at Week 8
    -35.6 ± 20.86
    -37.1 ± 18.97
        Change at Week 12
    -40.4 ± 19.01
    -40.5 ± 19.45
        Change at Week 18
    -44.2 ± 18.96
    -44.2 ± 19.64
        Change at Week 26 (pre-dose)
    -47.2 ± 18.68
    -46.5 ± 19.96
    No statistical analyses for this end point

    Secondary: Change From Baseline in Physician’s Global Assessment of Arthritis (PGAA): Period 2

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    End point title
    Change From Baseline in Physician’s Global Assessment of Arthritis (PGAA): Period 2
    End point description
    The investigator assessed how the subject’s overall arthritis appeared at the time of the visit. This was an evaluation based on the subject’s disease symptoms, functional capacity and physical examination, and independent of the subject’s reported assessments of PGA (patient’s global assessment of arthritis) and PAAP (patient’s assessment of arthritis pain). The investigator’s response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled “None” and the 100 mm end labeled “Extreme”. The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    64.9 ± 15.21
    66.3 ± 15.34
    67.0 ± 15.56
        Change at Week 26
    -47.7 ± 18.09
    -45.5 ± 19.80
    -49.2 ± 18.77
        Change at Week 30
    -47.9 ± 20.02
    -46.5 ± 19.52
    -49.6 ± 18.53
        Change at Week 36
    -47.3 ± 20.22
    -45.4 ± 19.46
    -49.5 ± 20.47
        Change at Week 44
    -49.1 ± 18.34
    -46.9 ± 20.16
    -50.5 ± 20.50
        Change at Week 52 (pre-dose)
    -47.9 ± 18.89
    -48.4 ± 17.75
    -52.1 ± 20.01
    No statistical analyses for this end point

    Secondary: Change From Baseline in Physician’s Global Assessment of Arthritis (PGAA): Period 3

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    End point title
    Change From Baseline in Physician’s Global Assessment of Arthritis (PGAA): Period 3
    End point description
    The investigator assessed how the subject’s overall arthritis appeared at the time of the visit. This was an evaluation based on the subject’s disease symptoms, functional capacity and physical examination, and independent of the subject’s reported assessments of PGA (patient’s global assessment of arthritis) and PAAP (patient’s assessment of arthritis pain). The investigator’s response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled “None” and the 100 mm end labeled “Extreme”. The analysis population included all subjects enrolled in period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    65.4 ± 14.57
    66.4 ± 15.55
    67.0 ± 15.73
    66.1 ± 15.09
        Change at Week 52
    -48.9 ± 17.82
    -48.5 ± 17.87
    -52.2 ± 19.62
    -49.7 ± 18.33
        Change at Week 56
    -50.5 ± 16.95
    -47.7 ± 20.00
    -51.6 ± 21.18
    -50.1 ± 18.85
        Change at Week 66
    -49.4 ± 18.93
    -49.1 ± 18.21
    -51.1 ± 20.29
    -49.8 ± 19.09
        Change at Week 76
    -50.9 ± 17.87
    -49.7 ± 21.07
    -52.3 ± 20.57
    -51.0 ± 19.33
        Change at Week 78
    -52.3 ± 17.40
    -50.8 ± 19.42
    -52.5 ± 19.96
    -52.0 ± 18.55
    No statistical analyses for this end point

    Secondary: Change From Baseline in Patient’s Assessment of Arthritis Pain (PAAP): Period 1

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    End point title
    Change From Baseline in Patient’s Assessment of Arthritis Pain (PAAP): Period 1
    End point description
    Subjects assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    63.7 ± 18.42
    65.9 ± 19.61
        Change at Week 2
    -13.1 ± 18.59
    -13.9 ± 18.72
        Change at Week 4
    -18.5 ± 20.35
    -17.4 ± 20.30
        Change at Week 6
    -21.9 ± 21.92
    -21.7 ± 22.49
        Change at Week 8
    -24.8 ± 24.06
    -25.5 ± 23.18
        Change at Week 12
    -28.8 ± 24.80
    -28.5 ± 23.91
        Change at Week 18
    -31.5 ± 23.69
    -31.4 ± 25.48
        Change at Week 26 (pre-dose)
    -35.1 ± 24.62
    -33.5 ± 26.09
    No statistical analyses for this end point

    Secondary: Change From Baseline in Patient’s Assessment of Arthritis Pain (PAAP): Period 2

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    End point title
    Change From Baseline in Patient’s Assessment of Arthritis Pain (PAAP): Period 2
    End point description
    Subjects assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    63.5 ± 18.04
    65.6 ± 19.91
    64.4 ± 19.37
        Change at Week 26
    -35.4 ± 23.87
    -32.4 ± 25.68
    -36.0 ± 26.04
        Change at Week 30
    -36.3 ± 24.86
    -34.1 ± 26.40
    -37.6 ± 24.47
        Change at Week 36
    -35.5 ± 25.87
    -34.9 ± 25.74
    -39.4 ± 24.87
        Change at Week 44
    -38.6 ± 25.03
    -35.7 ± 26.16
    -38.3 ± 28.05
        Change at Week 52 (pre-dose)
    -37.4 ± 25.09
    -36.8 ± 24.05
    -40.6 ± 24.16
    No statistical analyses for this end point

    Secondary: Change From Baseline in Patient’s Assessment of Arthritis Pain (PAAP): Period 3

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    End point title
    Change From Baseline in Patient’s Assessment of Arthritis Pain (PAAP): Period 3
    End point description
    Subjects assessed the severity of their arthritis pain using a 100 mm Visual Analog Scale (VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain. The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    63.5 ± 17.99
    66.3 ± 19.98
    64.5 ± 19.05
    64.4 ± 18.75
        Change at Week 52
    -38.1 ± 25.06
    -37.3 ± 23.93
    -40.6 ± 23.96
    -38.5 ± 24.50
        Change at Week 56
    -39.1 ± 23.87
    -37.7 ± 25.07
    -40.1 ± 25.62
    -39.0 ± 24.57
        Change at Week 66
    -39.8 ± 24.74
    -39.2 ± 24.76
    -40.7 ± 26.42
    -39.9 ± 25.13
        Change at Week 76
    -41.3 ± 25.60
    -39.3 ± 25.95
    -42.4 ± 25.68
    -41.1 ± 25.67
        Change at Week 78
    -43.7 ± 25.17
    -41.4 ± 25.04
    -42.7 ± 26.09
    -42.9 ± 25.34
    No statistical analyses for this end point

    Secondary: Change From Baseline in Patient’s Global Assessment of Arthritis (PGA): Period 1

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    End point title
    Change From Baseline in Patient’s Global Assessment of Arthritis (PGA): Period 1
    End point description
    Subjects answered the following question, “Considering all the ways your arthritis affects you, how are you feeling today?” The subject’s response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled “Very Well” and the 100 mm end labeled “Very Poorly”. The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    64.4 ± 19.32
    68.1 ± 19.49
        Change at Week 2
    -13.8 ± 19.03
    -16.3 ± 18.30
        Change at Week 4
    -19.7 ± 20.85
    -21.2 ± 21.62
        Change at Week 6
    -22.2 ± 22.96
    -23.4 ± 22.69
        Change at Week 8
    -25.8 ± 24.01
    -28.4 ± 23.17
        Change at Week 12
    -29.3 ± 24.72
    -31.5 ± 24.36
        Change at Week 18
    -32.2 ± 24.57
    -34.2 ± 25.94
        Change at Week 26 (pre-dose)
    -36.2 ± 25.16
    -36.3 ± 26.21
    No statistical analyses for this end point

    Secondary: Change From Baseline in Patient’s Global Assessment of Arthritis (PGA): Period 2

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    End point title
    Change From Baseline in Patient’s Global Assessment of Arthritis (PGA): Period 2
    End point description
    Subjects answered the following question, “Considering all the ways your arthritis affects you, how are you feeling today?” The subject’s response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled “Very Well” and the 100 mm end labeled “Very Poorly”. The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    64.2 ± 19.05
    67.5 ± 21.02
    67.8 ± 17.59
        Change at Week 26
    -36.3 ± 24.47
    -35.3 ± 26.02
    -38.8 ± 25.71
        Change at Week 30
    -36.7 ± 26.11
    -35.5 ± 27.02
    -41.2 ± 22.34
        Change at Week 36
    -36.4 ± 26.51
    -36.0 ± 26.30
    -43.1 ± 22.31
        Change at Week 44
    -39.4 ± 25.01
    -36.7 ± 25.43
    -40.6 ± 26.49
        Change at Week 52 (pre-dose)
    -37.5 ± 25.88
    -38.6 ± 24.97
    -44.0 ± 22.94
    No statistical analyses for this end point

    Secondary: Change From Baseline in Patient’s Global Assessment of Arthritis (PGA): Period 3

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    End point title
    Change From Baseline in Patient’s Global Assessment of Arthritis (PGA): Period 3
    End point description
    Subjects answered the following question, “Considering all the ways your arthritis affects you, how are you feeling today?” The subject’s response was recorded using a 100 mm visual analog scale (VAS), with the 0 mm end labeled “Very Well” and the 100 mm end labeled “Very Poorly”. The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    64.1 ± 19.02
    67.5 ± 21.04
    68.1 ± 17.30
    65.9 ± 19.17
        Change at Week 52
    -38.3 ± 25.54
    -39.0 ± 24.94
    -43.9 ± 22.79
    -39.9 ± 24.80
        Change at Week 56
    -39.7 ± 24.47
    -39.1 ± 25.61
    -43.4 ± 25.16
    -40.5 ± 24.93
        Change at Week 66
    -40.6 ± 25.04
    -39.7 ± 24.43
    -43.3 ± 26.63
    -41.1 ± 25.29
        Change at Week 76
    -41.7 ± 26.94
    -40.5 ± 26.56
    -45.3 ± 23.51
    -42.3 ± 26.05
        Change at Week 78
    -43.8 ± 26.05
    -42.0 ± 25.09
    -45.4 ± 24.61
    -43.8 ± 25.44
    No statistical analyses for this end point

    Secondary: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 1

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    End point title
    Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 1
    End point description
    HAQ-DI assesses difficulty degree a subject had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each category consisted of 2-3 items. For each question, difficulty level was scored from 0 to 3 with 0 meaning “no difficulty”, 1 as “some difficulty”, 2 as “much difficulty”, and 3 as “unable to do”. Any activity that required assistance from others or required use of assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 meaning “no difficulty”, 1 as “some difficulty”, 2 as “much difficulty”, and 3 as “unable to do”. Higher score indicate more difficulty in performing daily living activities. Analysis population included all subjects were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    1.519 ± 0.6009
    1.673 ± 0.6378
        Change at Week 2
    -0.254 ± 0.4018
    -0.288 ± 0.4383
        Change at Week 4
    -0.338 ± 0.4720
    -0.375 ± 0.4555
        Change at Week 6
    -0.426 ± 0.5114
    -0.454 ± 0.5350
        Change at Week 8
    -0.480 ± 0.5253
    -0.520 ± 0.5457
        Change at Week 12
    -0.530 ± 0.5218
    -0.543 ± 0.5882
        Change at Week 18
    -0.583 ± 0.5704
    -0.630 ± 0.6344
        Change at Week 26 (pre-dose)
    -0.654 ± 0.6262
    -0.674 ± 0.6618
    No statistical analyses for this end point

    Secondary: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 2

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    End point title
    Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 2
    End point description
    HAQ-DI assesses difficulty degree a subject had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each category consisted of 2-3 items. For each question, difficulty level was scored from 0 to 3 with 0 meaning “no difficulty”, 1 as “some difficulty”, 2 as “much difficulty”, and 3 as “unable to do”. Any activity that required assistance from others or required use of assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 meaning “no difficulty”, 1 as “some difficulty”, 2 as “much difficulty”, and 3 as “unable to do”. Higher score indicate more difficulty in performing daily living activities. Analysis population included all subjects were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    1.514 ± 0.5920
    1.639 ± 0.6677
    1.666 ± 0.6271
        Change at Week 26
    -0.658 ± 0.6250
    -0.652 ± 0.6293
    -0.723 ± 0.6763
        Change at Week 30
    -0.681 ± 0.6379
    -0.650 ± 0.6673
    -0.772 ± 0.7113
        Change at Week 36
    -0.711 ± 0.6585
    -0.662 ± 0.6610
    -0.811 ± 0.7048
        Change at Week 44
    -0.726 ± 0.6605
    -0.690 ± 0.6414
    -0.834 ± 0.6956
        Change at Week 52 (pre-dose)
    -0.700 ± 0.6776
    -0.729 ± 0.6359
    -0.840 ± 0.6861
    No statistical analyses for this end point

    Secondary: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 3

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    End point title
    Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI): Period 3
    End point description
    HAQ-DI assesses difficulty degree a subject had experienced during the past week in 8 domains of daily activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip and other activities. Each category consisted of 2-3 items. For each question, difficulty level was scored from 0 to 3 with 0 meaning “no difficulty”, 1 as “some difficulty”, 2 as “much difficulty”, and 3 as “unable to do”. Any activity that required assistance from others or required use of assistive device would adjust to a minimum score of 2 to represent a more limited functional status. Overall score was the sum of scores divided by the number of domains answered. Total possible score range was 0-3 with 0 meaning “no difficulty”, 1 as “some difficulty”, 2 as “much difficulty”, and 3 as “unable to do”. Higher score indicate more difficulty in performing daily living activities. Analysis population included all subjects were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    1.528 ± 0.5941
    1.632 ± 0.6711
    1.684 ± 0.6164
    1.592 ± 0.6212
        Change at Week 52
    -0.719 ± 0.6809
    -0.737 ± 0.6379
    -0.836 ± 0.6877
    -0.752 ± 0.6731
        Change at Week 56
    -0.735 ± 0.6733
    -0.754 ± 0.6149
    -0.801 ± 0.6549
    -0.756 ± 0.6543
        Change at Week 66
    -0.731 ± 0.6656
    -0.731 ± 0.6493
    -0.828 ± 0.6872
    -0.755 ± 0.6672
        Change at Week 76
    -0.751 ± 0.6725
    -0.789 ± 0.7225
    -0.867 ± 0.7066
    -0.788 ± 0.6931
        Change at Week 78
    -0.781 ± 0.6571
    -0.800 ± 0.7240
    -0.881 ± 0.7194
    -0.811 ± 0.6894
    No statistical analyses for this end point

    Secondary: Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP): Period 1

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    End point title
    Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP): Period 1
    End point description
    Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant. The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks1, 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: mg/L
    arithmetic mean (standard deviation)
        Baseline
    21.3 ± 22.69
    22.8 ± 25.26
        Change at Week 1
    -12.6 ± 19.84
    -13.4 ± 24.83
        Change at Week 2
    -11.5 ± 19.10
    -13.1 ± 20.74
        Change at Week 4
    -11.2 ± 19.94
    -12.6 ± 23.16
        Change at Week 6
    -11.3 ± 18.73
    -12.6 ± 24.74
        Change at Week 8
    -9.1 ± 22.65
    -12.0 ± 25.68
        Change at Week 12
    -9.5 ± 22.81
    -12.2 ± 25.59
        Change at Week 18
    -11.4 ± 20.67
    -12.3 ± 26.93
        Change at Week 26 (pre-dose)
    -11.1 ± 21.92
    -13.6 ± 26.47
    No statistical analyses for this end point

    Secondary: Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP): Period 2

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    End point title
    Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP): Period 2
    End point description
    Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant. The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: mg/L
    arithmetic mean (standard deviation)
        Baseline
    21.2 ± 22.47
    22.0 ± 24.51
    22.3 ± 25.93
        Change at Week 26
    -11.3 ± 21.70
    -11.2 ± 27.76
    -15.8 ± 25.10
        Change at Week 30
    -11.3 ± 19.76
    -10.4 ± 26.85
    -15.0 ± 24.50
        Change at Week 36
    -10.6 ± 22.58
    -11.8 ± 25.41
    -12.5 ± 30.36
        Change at Week 44
    -9.9 ± 22.08
    -11.1 ± 27.01
    -14.8 ± 26.80
        Change at Week 52 (pre-dose)
    -10.6 ± 20.84
    -11.8 ± 23.85
    -12.8 ± 28.49
    No statistical analyses for this end point

    Secondary: Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP): Period 3

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    End point title
    Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP): Period 3
    End point description
    Serum samples were analyzed to determine the level of hs-CRP, which was an acute-phase reactant. The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: mg/L
    arithmetic mean (standard deviation)
        Baseline
    20.4 ± 20.43
    22.3 ± 25.30
    22.7 ± 26.49
    21.4 ± 23.25
        Change at Week 52
    -10.7 ± 20.81
    -11.9 ± 24.04
    -12.9 ± 28.57
    -11.5 ± 23.70
        Change at Week 56
    -9.9 ± 25.29
    -11.7 ± 26.66
    -14.3 ± 26.64
    -11.4 ± 25.97
        Change at Week 66
    -11.1 ± 21.24
    -9.1 ± 25.83
    -13.2 ± 26.97
    -11.2 ± 23.87
        Change at Week 76
    -12.1 ± 20.58
    -9.8 ± 22.03
    -11.9 ± 28.83
    -11.5 ± 23.15
        Change at Week 78
    -9.7 ± 24.68
    -11.9 ± 22.90
    -13.3 ± 27.06
    -11.1 ± 24.90
    No statistical analyses for this end point

    Secondary: Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 1

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    End point title
    Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 1
    End point description
    The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient’s global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    5.9 ± 0.87
    6.1 ± 0.90
        Change at Week 2
    -1.2 ± 0.91
    -1.1 ± 0.92
        Change at Week 4
    -1.5 ± 1.00
    -1.6 ± 1.01
        Change at Week 6
    -1.9 ± 1.19
    -1.9 ± 1.22
        Change at Week 8
    -2.0 ± 1.19
    -2.2 ± 1.22
        Change at Week 12
    -2.2 ± 1.20
    -2.3 ± 1.26
        Change at Week 18
    -2.5 ± 1.20
    -2.6 ± 1.33
        Change at Week 26 (pre-dose)
    -2.7 ± 1.18
    -2.8 ± 1.31
    No statistical analyses for this end point

    Secondary: Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 2

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    End point title
    Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 2
    End point description
    The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient’s global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    5.9 ± 0.85
    6.1 ± 0.85
    6.0 ± 0.98
        Change at Week 26
    -2.7 ± 1.16
    -2.7 ± 1.28
    -3.0 ± 1.25
        Change at Week 30
    -2.8 ± 1.25
    -2.7 ± 1.31
    -3.1 ± 1.17
        Change at Week 36
    -2.8 ± 1.29
    -2.8 ± 1.32
    -3.1 ± 1.20
        Change at Week 44
    -3.0 ± 1.14
    -2.9 ± 1.26
    -3.2 ± 1.21
        Change at Week 52 (pre-dose)
    -2.9 ± 1.23
    -2.9 ± 1.33
    -3.3 ± 1.26
    No statistical analyses for this end point

    Secondary: Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 3

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    End point title
    Change From Baseline in Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]): Period 3
    End point description
    The DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient’s global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. Higher score indicate more disease activity. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L).The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline
    5.9 ± 0.86
    6.1 ± 0.86
    6.0 ± 0.96
    6.0 ± 0.89
        Change at Week 52
    -2.9 ± 1.21
    -2.9 ± 1.32
    -3.3 ± 1.25
    -3.0 ± 1.26
        Change at Week 56
    -3.0 ± 1.22
    -2.9 ± 1.34
    -3.3 ± 1.29
    -3.0 ± 1.27
        Change at Week 66
    -3.0 ± 1.19
    -3.0 ± 1.34
    -3.3 ± 1.26
    -3.1 ± 1.24
        Change at Week 76
    -3.1 ± 1.18
    -3.0 ± 1.34
    -3.4 ± 1.29
    -3.2 ± 1.25
        Change at Week 78
    -3.2 ± 1.21
    -3.1 ± 1.37
    -3.4 ± 1.39
    -3.2 ± 1.30
    No statistical analyses for this end point

    Secondary: Number of Subjects Achieving European League Against Rheumatism (EULAR) Response: Period 1

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    End point title
    Number of Subjects Achieving European League Against Rheumatism (EULAR) Response: Period 1
    End point description
    EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline >1.2 and DAS28 =<3.2. Moderate response was achieved if DAS28 improvement from baseline >0.6 to =<1.2 and DAS28 =<5.1; or DAS improvement from baseline >1.2 and DAS28 >3.2. No response was achieved if DAS improvement from baseline =<0.6 (no matter present DAS28 score); or DAS improvement from baseline >0.6 to =<1.2 and DAS28 >5.1. The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: subjects
        Week 2 good response
    18
    20
        Week 2 moderate response
    161
    136
        Week 2 no response
    110
    133
        Week 4 good response
    48
    42
        Week 4 moderate response
    173
    168
        Week 4 no response
    71
    81
        Week 6 good response
    69
    65
        Week 6 moderate response
    178
    173
        Week 6 no response
    48
    55
        Week 8 good response
    93
    89
        Week 8 moderate response
    160
    160
        Week 8 no response
    38
    43
        Week 12 good response
    104
    107
        Week 12 moderate response
    149
    149
        Week 12 no response
    37
    37
        Week 18 good response
    137
    132
        Week 18 moderate response
    134
    125
        Week 18 no response
    21
    29
        Week 26 (pre-dose) good response
    162
    147
        Week 26 (pre-dose) moderate response
    110
    102
        Week 26 (pre-dose) no response
    16
    27
    No statistical analyses for this end point

    Secondary: Number of Subjects Achieving European League Against Rheumatism (EULAR) Response: Period 2

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    End point title
    Number of Subjects Achieving European League Against Rheumatism (EULAR) Response: Period 2
    End point description
    EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline >1.2 and DAS28 =<3.2. Moderate response was achieved if DAS28 improvement from baseline >0.6 to =<1.2 and DAS28 =<5.1; or DAS improvement from baseline >1.2 and DAS28 >3.2. No response was achieved if DAS improvement from baseline =<0.6 (no matter present DAS28 score); or DAS improvement from baseline >0.6 to =<1.2 and DAS28 >5.1. The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: subjects
        Week 26 good response
    161
    67
    80
        Week 26 moderate response
    109
    53
    45
        Week 26 no response
    13
    13
    9
        Week 30 good response
    160
    64
    83
        Week 30 moderate response
    106
    54
    45
        Week 30 no response
    13
    12
    3
        Week 36 good response
    158
    59
    86
        Week 36 moderate response
    97
    60
    39
        Week 36 no response
    19
    7
    5
        Week 44 good response
    170
    62
    83
        Week 44 moderate response
    92
    60
    45
        Week 44 no response
    5
    3
    2
        Week 52 (pre-dose) good response
    169
    61
    85
        Week 52 (pre-dose) moderate response
    86
    54
    40
        Week 52 (pre-dose) no response
    12
    8
    2
    No statistical analyses for this end point

    Secondary: Number of Subjects Achieving European League Against Rheumatism (EULAR) Response: Period 3

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    End point title
    Number of Subjects Achieving European League Against Rheumatism (EULAR) Response: Period 3
    End point description
    EULAR response was based on DAS28 EULAR response criteria. Good response was achieved if DAS28 improvement from baseline >1.2 and DAS28 =<3.2. Moderate response was achieved if DAS28 improvement from baseline >0.6 to =<1.2 and DAS28 =<5.1; or DAS improvement from baseline >1.2 and DAS28 >3.2. No response was achieved if DAS improvement from baseline =<0.6 (no matter present DAS28 score); or DAS improvement from baseline >0.6 to =<1.2 and DAS28 >5.1. The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: subjects
        Week 52 good response
    169
    60
    85
    314
        Week 52 moderate response
    80
    53
    39
    172
        Week 52 no response
    9
    8
    2
    19
        Week 56 good response
    171
    63
    84
    318
        Week 56 moderate response
    72
    50
    36
    158
        Week 56 no response
    12
    8
    4
    24
        Week 66 good response
    174
    62
    86
    322
        Week 66 moderate response
    69
    48
    33
    150
        Week 66 no response
    10
    6
    3
    19
        Week 76 good response
    170
    59
    81
    310
        Week 76 moderate response
    64
    45
    27
    136
        Week 76 no response
    7
    5
    5
    17
        Week 78 good response
    167
    67
    89
    323
        Week 78 moderate response
    65
    40
    26
    131
        Week 78 no response
    7
    6
    5
    18
    No statistical analyses for this end point

    Secondary: Number of Subjects Achieving Disease Activity Score Remission (DAS <2.6): Period 1

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    End point title
    Number of Subjects Achieving Disease Activity Score Remission (DAS <2.6): Period 1
    End point description
    DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient’s global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) <2.6 indicates remission. Analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: subjects
        Baseline
    0
    0
        Week 2
    9
    8
        Week 4
    20
    17
        Week 6
    35
    34
        Week 8
    49
    48
        Week 12
    63
    62
        Week 18
    71
    81
        Week 26 (pre-dose)
    87
    99
    No statistical analyses for this end point

    Secondary: Number of Subjects Achieving Disease Activity Score Remission (DAS <2.6): Period 2

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    End point title
    Number of Subjects Achieving Disease Activity Score Remission (DAS <2.6): Period 2
    End point description
    DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient’s global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) <2.6 indicates remission. Analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: subjects
        Week 26
    86
    41
    58
        Week 30
    96
    42
    51
        Week 36
    106
    41
    54
        Week 44
    109
    44
    51
        Week 52 (pre-dose)
    107
    40
    59
    No statistical analyses for this end point

    Secondary: Number of Subjects Achieving Disease Activity Score Remission (DAS <2.6): Period 3

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    End point title
    Number of Subjects Achieving Disease Activity Score Remission (DAS <2.6): Period 3
    End point description
    DAS assessment is a continuous composite measure derived using differential weighting given to each component. The components of the DAS28-4 (CRP) assessment included: tender joint count with 28 joints assessed, swollen joint count with 28 joints assessed, high-sensitivity C-reactive protein (hs-CRP) and patient’s global assessment of arthritis (PGA). DAS28-4 (CRP) was calculated as 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 ln(CRP [mg/L] +1) + 0.014 (PGA [mm]) + 0.96. The possible lowest score is 0.96. The possible highest score is difficult to be determined, due to indeterminable nature of hs-CRP level; assuming hs-CRP level is 0 to 500 mg/L, the possible highest score would be 6.8 (when hs-CRP is 0) to 9.04 (when hs-CRP is 500 mg/L). Higher score indicate more disease activity; DAS28-4 (CRP) <2.6 indicates remission. Analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: subjects
        Week 52
    107
    39
    59
    205
        Week 56
    111
    46
    57
    214
        Week 66
    108
    52
    61
    221
        Week 76
    122
    45
    60
    227
        Week 78
    130
    51
    68
    249
    No statistical analyses for this end point

    Secondary: Number of Subjects Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response:Period 1

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    End point title
    Number of Subjects Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response:Period 1
    End point description
    Subjects were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =<1; or the score on the simplified disease activity index (SDAI) was =<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician’s global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL). The analysis population included all subjects who were randomized to study treatment. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 12, 18 and 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    300
    Units: subjects
        Week 2
    2
    3
        Week 4
    3
    5
        Week 6
    14
    11
        Week 8
    16
    21
        Week 12
    24
    24
        Week 18
    29
    44
        Week 26 (pre-dose)
    38
    44
    No statistical analyses for this end point

    Secondary: Number of Subjects Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 2

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    End point title
    Number of Subjects Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 2
    End point description
    Subjects were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =<1; or the score on the simplified disease activity index (SDAI) was =<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician’s global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL). The analysis population included all subjects who completed the Period 2 randomization call. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 26, 30, 36, 44 and 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    134
    Units: subjects
        Week 26
    38
    26
    19
        Week 30
    50
    26
    27
        Week 36
    49
    21
    27
        Week 44
    56
    29
    34
        Week 52 (pre-dose)
    53
    28
    35
    No statistical analyses for this end point

    Secondary: Number of Subjects Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 3

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    End point title
    Number of Subjects Achieving American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Response: Period 3
    End point description
    Subjects were considered to be in ACR/EULAR remission when either of the following criteria was met: scores on the tender joint count, swollen joint count, hs-CRP (mg/dL) and PGA (0-10 cm scale) were all =<1; or the score on the simplified disease activity index (SDAI) was =<3.3. SDAI score was the sum of tender joint count (28), swollen joint count (28), PGA (0-10 cm scale), physician’s global assessment of arthritis (PGAA, 0-10 cm scale) and hs-CRP (mg/dL). The analysis population included all subjects enrolled in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Weeks 52, 56, 66, 76 and 78
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    259
    121
    127
    507
    Units: subjects
        Week 52
    53
    27
    34
    114
        Week 56
    63
    28
    30
    121
        Week 66
    57
    31
    29
    117
        Week 76
    69
    27
    36
    132
        Week 78
    77
    34
    43
    154
    No statistical analyses for this end point

    Secondary: Serum Concentration Versus Time Summary: Period 1

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    End point title
    Serum Concentration Versus Time Summary: Period 1
    End point description
    The analysis population included all subjects who received study drug and provided at least 1 post-dose drug concentration measurement in Period 1. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Days 1, 15, 43, 85 and 183, and at any time during Day 8 visit
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    299
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 1 (Week 0)
    104.8 ± 1125.1
    187.3 ± 1372.7
        Day 8 (Week 1)
    3756 ± 1829.8
    3488 ± 1938.2
        Day 15 (Week 2)
    3349 ± 1601.0
    3025 ± 1729.7
        Day 43 (Week 6)
    6205 ± 3525.6
    5526 ± 3249.2
        Day 85 (Week 12)
    7575 ± 4725.1
    6531 ± 4302.5
        Day 183 (Week 26)
    8244 ± 5494.6
    7190 ± 5402.6
    No statistical analyses for this end point

    Secondary: Serum Concentration Versus Time Summary: Period 2

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    End point title
    Serum Concentration Versus Time Summary: Period 2
    End point description
    The analysis population included all subjects who received study drug and provided at least 1 post-dose drug concentration measurement in Period 2. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Days 183, 211, 253 and 365
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    133
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 183 (Week 26)
    8346 ± 5463.5
    7058 ± 5174.1
    7557 ± 5492.8
        Day 211 (Week 30)
    8314 ± 5728.6
    6831 ± 5147.2
    7626 ± 5335.7
        Day 253 (Week 36)
    8066 ± 5297.3
    7063 ± 5234.2
    8198 ± 5627.9
        Day 365 (Week 52)
    7491 ± 4946.9
    6252 ± 5054.5
    8157 ± 5648.5
    No statistical analyses for this end point

    Secondary: Serum Concentration Versus Time Summary: Period 3

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    End point title
    Serum Concentration Versus Time Summary: Period 3
    End point description
    The analysis population included all subjects who received study drug and provided at least 1 post-dose drug concentration measurement in Period 3. Not all subjects had data for each visit.
    End point type
    Secondary
    End point timeframe
    Pre-dose on Days 365, 393, 463, 547 and 575
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    258
    120
    127
    505
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 365 (Week 52)
    7539 ± 4933.6
    6298 ± 5063.7
    8157 ± 5648.5
    7398 ± 5184.6
        Day 393 (Week 56)
    7402 ± 5190.6
    6261 ± 4999.6
    8345 ± 5255.0
    7362 ± 5202.5
        Day 463 (Week 66)
    7364 ± 5118.5
    6482 ± 4879.4
    8118 ± 5507.9
    7340 ± 5183.0
        Day 547 (Week 78)
    6728 ± 5003.2
    6217 ± 5118.7
    7388 ± 5380.7
    6774 ± 5134.7
        Day 575 (Follow-up)
    3355 ± 3239.2
    3069 ± 3393.2
    3802 ± 3781.1
    3397 ± 3419.7
    No statistical analyses for this end point

    Secondary: Number of Subjects With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 1

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    End point title
    Number of Subjects With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 1
    End point description
    Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer >=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer >=0.70. The analysis population included all randomized subjects who received at least 1 dose of study drug, and had at least 1 ADA measurement in Period 1, analyzed by actual treatment received.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    298
    Units: subjects
        ADA
    132
    151
        NAb
    41
    42
    No statistical analyses for this end point

    Secondary: Number of Subjects With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 2

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    End point title
    Number of Subjects With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 2
    End point description
    Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer >=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer >=0.70. The analysis population included all randomized subjects who received at least 1 dose of study treatment in Period 1, and received at least 1 dose of study treatment in Period 2, and had at least 1 ADA measurement in Period 2, analyzed by actual treatment received.
    End point type
    Secondary
    End point timeframe
    Week 26 dosing up to Week 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    134
    133
    Units: subjects
        ADA
    134
    73
    61
        NAb
    46
    18
    16
    No statistical analyses for this end point

    Secondary: Number of Subjects With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 3

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    End point title
    Number of Subjects With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb): Period 3
    End point description
    Serum samples were analyzed for the presence or absence of ADA using a semi-quantitative electrochemiluminescent (ECL) assay, and ADA positive was defined as ADA titer >=1.88. Serum samples tested positive for ADA were further analyzed for the presence or absence of NAb using a semi-quantitative cell-based assay, and NAb positive was defined as NAb titer >=0.70. The analysis population included all subjects enrolled and treated in Period 3 who had at least 1 ADA measurement in Period 3.
    End point type
    Secondary
    End point timeframe
    Week 52 dosing up to follow-up visit (Week 92)
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    256
    120
    126
    502
    Units: subjects
        ADA
    119
    65
    59
    243
        NAb
    54
    30
    21
    105
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 1

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    End point title
    Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 1
    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 AEs for Period 1 were events between first dose of study drug in Period 1 and up to Week 26 pre-dose assessments that were absent before treatment or that worsened relative to pre-treatment state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs. The analysis population included all randomized subjects who received at least 1 dose of study treatment, analyzed by actual treatment received.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) up to Week 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    299
    Units: subjects
        All-causality TEAE
    143
    143
        All-causality SAE
    12
    13
        Treatment-related TEAE
    55
    69
        Treatment-related SAE
    5
    4
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 2

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    End point title
    Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 2
    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 AEs for Period 2 were events between first dose of study drug in Period 2 and up to Week 52 pre-dose assessments that were absent before treatment or that worsened relative to prior state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs. The analysis population included all randomized subjects who received at least 1 dose of study treatment in Period 1, and received at least 1 dost of study treatment in Period 2, analyzed by actual treatment received.
    End point type
    Secondary
    End point timeframe
    Week 26 dosing up to Week 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    135
    133
    Units: subjects
        All-causality TEAE
    123
    60
    51
        All-causality SAE
    4
    6
    3
        Treatment-related TEAE
    32
    22
    18
        Treatment-related SAE
    2
    2
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 3

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    End point title
    Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Related TEAEs: Period 3
    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 AEs for Period 3 were events between first dose of study drug in Period 3 and up to Week 92 visit that were absent before treatment or that worsened relative to prior state. Treatment-related TEAE was any untoward medical occurrence attributed to study drug. AEs included both serious and non-serious AEs. The analysis population included all subjects enrolled and treated in Period 3.
    End point type
    Secondary
    End point timeframe
    Week 52 dosing up to follow-up visit (Week 92)
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    258
    120
    127
    505
    Units: subjects
        All-causality TEAE
    110
    61
    47
    218
        All-causality SAE
    9
    9
    3
    21
        Treatment-related TEAE
    27
    13
    17
    57
        Treatment-related SAE
    0
    3
    0
    3
    No statistical analyses for this end point

    Secondary: Number of Subjects With Laboratory Abnormalities: Period 1

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    End point title
    Number of Subjects With Laboratory Abnormalities: Period 1
    End point description
    Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of subjects with any laboratory abnormality during Period 1 (without regard to baseline abnormality) is presented. The analysis population included all randomized subjects who received at least 1 dose of study treatment and had laboratory test in Period 1, analyzed by actual treatment received.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) up to Week 26 (pre-dose)
    End point values
    Period 1: PF-06410293 Period 1: Adalimumab-EU
    Number of subjects analysed
    297
    298
    Units: subjects
    181
    180
    No statistical analyses for this end point

    Secondary: Number of Subjects With Laboratory Abnormalities: Period 2

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    End point title
    Number of Subjects With Laboratory Abnormalities: Period 2
    End point description
    Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of subjects with any laboratory abnormality during Period 2 (without regard to baseline abnormality) is presented. The analysis population included all randomized subjects who received at least 1 dose of study treatment in Period 1, and received at least 1 dost of study treatment in Period 2, and had laboratory test in Period 2, analyzed by actual treatment received.
    End point type
    Secondary
    End point timeframe
    Week 26 dosing up to Week 52 (pre-dose)
    End point values
    Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 2: Adalimumab-EU/PF-06410293
    Number of subjects analysed
    283
    134
    133
    Units: subjects
    171
    85
    73
    No statistical analyses for this end point

    Secondary: Number of Subjects With Laboratory Abnormalities: Period 3

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    End point title
    Number of Subjects With Laboratory Abnormalities: Period 3
    End point description
    Laboratory evaluation included hematology, clinical chemistry, and urinalysis. Each parameter was evaluated against commonly used and widely accepted criteria. Number of subjects with any laboratory abnormality during Period 3 (without regard to baseline abnormality) is presented. The analysis population included all subjects enrolled and treated in Period 3 who had laboratory test in Period 3.
    End point type
    Secondary
    End point timeframe
    Week 52 dosing up to follow-up visit (Week 92)
    End point values
    Period 3: PF-06410293/PF-06410293/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293 Period 3 Total
    Number of subjects analysed
    256
    120
    126
    502
    Units: subjects
    176
    77
    77
    330
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects Who Achieved Delivery Success in Sub-study

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    End point title
    Percentage of Subjects Who Achieved Delivery Success in Sub-study
    End point description
    A sub-study was conducted to determine whether subjects or their non-healthcare professional caregivers could safely and effectively administer PF-06410293 with the sponsor’s prefilled pen (PFP) device. The analysis population included all subjects in the sub-study. Not all subjects had data for each visit.
    End point type
    Other pre-specified
    End point timeframe
    Weeks 56, 58, 60, 62, 64, 66
    End point values
    Sub-study: PF-06410293 PFP
    Number of subjects analysed
    50
    Units: percentage of subjects
    number (not applicable)
        Week 56
    100.0
        Week 58
    100.0
        Week 60
    100.0
        Week 62
    100.0
        Week 64
    100.0
        Week 66
    100.0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first dose of study drug to Week 92
    Adverse event reporting additional description
    The same event may appear as both an AE and a SAE. However, what is presented are distinct events. Medical Dictionary for Regulatory Affairs (MedDRA) Version 20.0 was used for Periods 1 and 2; and Version 20.1 was used for Period 3.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0; 20.1
    Reporting groups
    Reporting group title
    Period 1: PF-06410293
    Reporting group description
    This reporting group refers to the subjects who were randomized to the PF-06410293 group in Period 1, where PF-06410293 40 mg was administered every other week by subcutaneous injection.

    Reporting group title
    Period 1: Adalimumab-EU
    Reporting group description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1, where adalimumab-EU 40 mg was administered every other week by subcutaneous injection.

    Reporting group title
    Period 2: PF-06410293/PF-06410293
    Reporting group description
    This reporting group refers to the subjects who were randomized to the PF-06410293 group in Period 1 and continued to receive PF-06410293 in Period 2. PF-06410293 40 mg was administered every other week by subcutaneous injection in both periods.

    Reporting group title
    Period 2: Adalimumab-EU/Adalimumab-EU
    Reporting group description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1 and remained in the adalimumab-EU group in Period 2. Adalimumab-EU 40 mg was administered every other week by subcutaneous injection in both periods.

    Reporting group title
    Period 3: PF-06410293/PF-06410293/PF-06410293
    Reporting group description
    This reporting group refers to the subjects who were randomized to the PF-06410293 group in Period 1 and continued to receive PF-06410293 in Period 2 and Period 3. PF-06410293 40 mg was administered every other week by subcutaneous injection in all 3 periods.

    Reporting group title
    Period 2: Adalimumab-EU/PF-06410293
    Reporting group description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1 and switched to PF-06410293 in Period 2. Study drug 40 mg was administered every other week by subcutaneous injection in both periods.

    Reporting group title
    Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293
    Reporting group description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1, remained in the adalimumab-EU group in Period 2 and received PF-06410293 in Period 3. Study drug 40 mg was administered every other week by subcutaneous injection in all 3 periods.

    Reporting group title
    Period 3: Adalimumab-EU/PF-06410293/PF-06410293
    Reporting group description
    This reporting group refers to the subjects who were randomized to the adalimumab-EU group in Period 1 and switched to PF-06410293 from Period 2 and continued on PF-06410293 in Period 3. Study drug 40 mg was administered every other week by subcutaneous injection in all 3 periods.

    Serious adverse events
    Period 1: PF-06410293 Period 1: Adalimumab-EU Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 3: PF-06410293/PF-06410293/PF-06410293 Period 2: Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 297 (4.04%)
    13 / 299 (4.35%)
    4 / 283 (1.41%)
    6 / 135 (4.44%)
    9 / 258 (3.49%)
    3 / 133 (2.26%)
    9 / 120 (7.50%)
    3 / 127 (2.36%)
         number of deaths (all causes)
    0
    1
    0
    0
    0
    0
    1
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    1 / 135 (0.74%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibroadenoma of breast
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    1 / 135 (0.74%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer stage II
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial adenocarcinoma
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    1 / 283 (0.35%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Intentional self-injury
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Panic attack
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Foot fracture
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    1 / 135 (0.74%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    1 / 133 (0.75%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heat stroke
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    1 / 258 (0.39%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    1 / 258 (0.39%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    1 / 135 (0.74%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    1 / 283 (0.35%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Microvascular coronary artery disease
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    1 / 258 (0.39%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 299 (0.67%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paranasal cyst
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    1 / 283 (0.35%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    1 / 133 (0.75%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    1 / 133 (0.75%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    1 / 283 (0.35%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Renal and urinary disorders
    Pelvi-ureteric obstruction
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive nephropathy
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Toxic skin eruption
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    1 / 283 (0.35%)
    0 / 135 (0.00%)
    1 / 258 (0.39%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Toxic nodular goitre
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    1 / 258 (0.39%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 297 (0.00%)
    1 / 299 (0.33%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 297 (0.00%)
    2 / 299 (0.67%)
    0 / 283 (0.00%)
    1 / 135 (0.74%)
    1 / 258 (0.39%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 297 (0.34%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    1 / 135 (0.74%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear infection
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    1 / 283 (0.35%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    1 / 135 (0.74%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    1 / 258 (0.39%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    1 / 258 (0.39%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    1 / 127 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    2 / 258 (0.78%)
    0 / 133 (0.00%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    0 / 283 (0.00%)
    0 / 135 (0.00%)
    0 / 258 (0.00%)
    0 / 133 (0.00%)
    1 / 120 (0.83%)
    0 / 127 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Period 1: PF-06410293 Period 1: Adalimumab-EU Period 2: PF-06410293/PF-06410293 Period 2: Adalimumab-EU/Adalimumab-EU Period 3: PF-06410293/PF-06410293/PF-06410293 Period 2: Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/Adalimumab-EU/PF-06410293 Period 3: Adalimumab-EU/PF-06410293/PF-06410293
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    21 / 297 (7.07%)
    18 / 299 (6.02%)
    15 / 283 (5.30%)
    5 / 135 (3.70%)
    24 / 258 (9.30%)
    6 / 133 (4.51%)
    14 / 120 (11.67%)
    15 / 127 (11.81%)
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
         subjects affected / exposed
    5 / 297 (1.68%)
    3 / 299 (1.00%)
    4 / 283 (1.41%)
    2 / 135 (1.48%)
    12 / 258 (4.65%)
    3 / 133 (2.26%)
    11 / 120 (9.17%)
    5 / 127 (3.94%)
         occurrences all number
    5
    3
    4
    2
    14
    3
    11
    6
    Infections and infestations
    Viral upper respiratory tract infection
         subjects affected / exposed
    21 / 297 (7.07%)
    18 / 299 (6.02%)
    15 / 283 (5.30%)
    5 / 135 (3.70%)
    1 / 258 (0.39%)
    6 / 133 (4.51%)
    0 / 120 (0.00%)
    0 / 127 (0.00%)
         occurrences all number
    22
    18
    17
    6
    1
    6
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 297 (0.00%)
    0 / 299 (0.00%)
    1 / 283 (0.35%)
    0 / 135 (0.00%)
    13 / 258 (5.04%)
    1 / 133 (0.75%)
    3 / 120 (2.50%)
    10 / 127 (7.87%)
         occurrences all number
    0
    0
    1
    0
    16
    1
    3
    10

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 May 2014
    Added urinalysis at Week 52 and fixed study day for follow up visit; Asia region was split to Japan and (South Korea + Taiwan) for randomization stratification; decreased entry methotrexate dose to 6 mg/week from 8 mg/week in geographic regions where 6 mg/week was a recommended initial dose by local guidance or standard of care; removed permission for use of any second disease modifying anti-rheumatic drug (DMARD) therapy, including sulfasalazine and/or anti-malarial drug during trial, and 4-week washout was required; Added recording of injection times after pharmacokinetic (PK) samples, and added time to 1 other injection before Week 12 primary endpoint that would not otherwise be recorded; added additional anti-drug antibody (ADA) sample at Week 6 as requested by the European Medicines Agency (EMA); changed ADA analysis plan to run all samples in both ADA assays as requested by the US Food and Drug Administration (FDA); added a return visit at Week 26 in subjects who withdrew before Week 26, as requested by the FDA; added follow-up telephone calls at Weeks 4 and 8 in subjects who withdrew before that, as requested by the EMA; added the option for an additional safety visit including laboratories at the discretion of the investigator, in case of any significant safety concerns at a phone follow-up, as requested by the EMA; updated permitted opioid drug tables to specify types of opioids allowed as background therapies versus those allowed as rescue therapies.
    08 Sep 2014
    Added safety telephone follow-up contact 16 weeks after final dose of study drug; added exclusion of subjects with prior history of severe allergic or anaphylactic reaction to a biologic drug, and clarified the washout period for prior investigational drugs to be the longer of the 2 stated options (4 weeks or 5 half-lives); pregnancy was added to treatment withdrawal criteria; added clarification and cross-references placed in protocol.
    25 Sep 2014
    Changed immunogenicity testing plan so that all immunogenicity samples were to be tested for ADA using a single, validated electrochemiluminescent (ECL) immunoassay for ADA against PF-06410293, instead of 2 assays; added another ADA sample, with a companion PK sample, in both treatment period 2(TP2) and TP3 for monitoring of post switch immunogenicity time course; modified follow-up procedures for subjects who discontinued before Week 26 to require more on-site visits in TP1; modified wording for subject discontinuation due to lack of efficacy to allow some investigator discretion; specified requirements for immediate release narcotic; added supplemental urine pregnancy testing as requested by Canadian regulatory authorities.
    15 Jul 2015
    Added DMARDs to the DMARD Washout Periods table.
    13 Nov 2015
    Modified optional isoniazid prophylaxis for high-risk subjects to be globally available where standard of care during adalimumab (study drug) treatment; added an appendix describing additional GCP and inspection responsibilities; clarified that the subject would select the most appropriate form of birth control in consultation with the investigator or designee; corrected the End of Treatment (EOT)/Early Termination (ET) urine pregnancy test to occur on Week 78/Visit 18 and not during Visit 17 at Week 76; clarified maximal paracetamol dose for chronic dosing (comparable to maximal chronic acetaminophen dose already listed); for RA flare treatment, added 1 oral corticosteroid (7 day) course after study Week 26 and altered the maximal intra articular corticosteroid dose to 40 mg methylprednisolone (or equivalent) per injection.
    16 May 2016
    Added a prefilled pen (PFP) sub-study during TP3 to evaluate the success of PF-06410293 administration by PFP.

    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

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/30111357