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    Clinical Trial Results:
    A RANDOMIZED, DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF THE MAINTENANCE OF EFFICACY OF ETANERCEPT PLUS DMARD(S) COMPARED WITH DMARD(S) ALONE IN SUBJECTS WITH RHEUMATOID ARTHRITIS AFTER ACHIEVING AN ADEQUATE RESPONSE WITH ETANERCEPT PLUS DMARD(S).

    Summary
    EudraCT number
    2011-005448-87
    Trial protocol
    HU   CZ  
    Global end of trial date
    27 Mar 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    12 Mar 2016
    First version publication date
    12 Mar 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B1801315
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01578850
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 East 42nd Street,, New York, United States, 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 800 718 1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 800 718 1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    16 Nov 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Mar 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Mar 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the maintenance of efficacy of the combination of ETN 50 mg once weekly plus MTX (±other DMARDs) therapy with that of MTX (±other DMARDs) at Week 52 in participants with moderately to severely active RA who have achieved LDA (DAS28-ESR<3.2) after 24 weeks of therapy with open-label ETN 50 mg once weekly plus MTX (±other DMARDs) in a treat to target paradigm. An adequate response is defined as a DAS28<3.2 at Week 24.
    Protection of trial subjects
    The study was conducted in accordance with legal and regulatory requirements, as well as the general principles set forth in the International Ethical Guidelines for Biomedical Research Involving Human Subjects (Council for International Organizations of Medical Sciences [CIOMS] 2002), Guidelines for GCP (International Conference on Harmonisation [ICH] 1996), and the Declaration of Helsinki (World Medical Association 1996 and 2008).
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    27 Jul 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    South Africa: 30
    Country: Number of subjects enrolled
    Taiwan: 24
    Country: Number of subjects enrolled
    Thailand: 34
    Country: Number of subjects enrolled
    Ukraine: 58
    Country: Number of subjects enrolled
    United Arab Emirates: 4
    Country: Number of subjects enrolled
    Jordan: 1
    Country: Number of subjects enrolled
    Brazil: 18
    Country: Number of subjects enrolled
    China: 29
    Country: Number of subjects enrolled
    Colombia: 13
    Country: Number of subjects enrolled
    Czech Republic: 50
    Country: Number of subjects enrolled
    Egypt: 41
    Country: Number of subjects enrolled
    Hungary: 5
    Country: Number of subjects enrolled
    Lebanon: 1
    Country: Number of subjects enrolled
    Malaysia: 13
    Country: Number of subjects enrolled
    Mexico: 53
    Country: Number of subjects enrolled
    Philippines: 35
    Country: Number of subjects enrolled
    Qatar: 2
    Country: Number of subjects enrolled
    Romania: 17
    Country: Number of subjects enrolled
    Russian Federation: 61
    Worldwide total number of subjects
    489
    EEA total number of subjects
    72
    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)
    452
    From 65 to 84 years
    37
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study consisted of Period 1 (an open-label, 24-week treat-to-target period), and Period 2 (a double-blind, randomized, 28-week period for participants who qualified for randomization).

    Pre-assignment
    Screening details
    The study was conducted in participants with rheumatoid arthritis (RA) who had moderate to severe disease activity despite methotrexate (MTX) therapy (≥10 mg/week) with or without other non-biologic disease modifying anti-rheumatic drugs (DMARDs) for at least 12 weeks prior to screening.

    Period 1
    Period 1 title
    Period 1
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded
    Blinding implementation details
    Study medication was not blinded during the open-label (period 1).

    Arms
    Arm title
    Open-Label Treatment
    Arm description
    Participants in open-label treatment received Etanercept (ETN) 50 milligram (mg) once a week (QW) with MTX (with or without other DMARDs).
    Arm type
    Experimental

    Investigational medicinal product name
    Etanercept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants in open-label treatment received ETN 50 mg QW with MTX (with or without other DMARDs).

    Number of subjects in period 1
    Open-Label Treatment
    Started
    489
    Completed
    452
    Not completed
    37
         Study Terminated by Sponsor
    3
         Insufficient Clinical Response
    1
         Adverse event, serious fatal
    1
         Does Not Meet Entrance Criteria
    12
         Adverse event, non-fatal
    11
         Consent withdrawn by subject
    9
    Period 2
    Period 2 title
    Period 2
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator
    Blinding implementation details
    The method was an electronic process. Blinding codes were only to be broken in emergency situations for reasons of participant safety.

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Etanercept
    Arm description
    Participants were randomized to receive ETN 50 mg QW with MTX (with or without other DMARDs).
    Arm type
    Active comparator

    Investigational medicinal product name
    Etanercept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants were randomized to receive ETN 50 mg QW with MTX (with or without other DMARDs).

    Arm title
    Placebo
    Arm description
    Participants were randomized to receive PBO 50 mg QW + MTX (with or without DMARDs).
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants were randomized to receive PBO 50 mg QW with MTX (with or without other DMARDs).

    Number of subjects in period 2
    Etanercept Placebo
    Started
    167
    176
    Completed
    154
    162
    Not completed
    13
    14
         Study Terminated by Sponsor
    5
    4
         Unspecified Reasons
    1
    -
         Insufficient Clinical Response
    1
    -
         Adverse event, non-fatal
    3
    6
         Consent withdrawn by subject
    2
    2
         Lost to follow-up
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Open-Label Treatment
    Reporting group description
    Participants in open-label treatment received Etanercept (ETN) 50 milligram (mg) once a week (QW) with MTX (with or without other DMARDs).

    Reporting group values
    Open-Label Treatment Total
    Number of subjects
    489 489
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    452 452
        From 65-84 years
    37 37
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    47.5 ± 12.24 -
    Gender, Male/Female
    Units: Participants
        Male
    423 423
        Female
    66 66

    End points

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    End points reporting groups
    Reporting group title
    Open-Label Treatment
    Reporting group description
    Participants in open-label treatment received Etanercept (ETN) 50 milligram (mg) once a week (QW) with MTX (with or without other DMARDs).
    Reporting group title
    Etanercept
    Reporting group description
    Participants were randomized to receive ETN 50 mg QW with MTX (with or without other DMARDs).

    Reporting group title
    Placebo
    Reporting group description
    Participants were randomized to receive PBO 50 mg QW + MTX (with or without DMARDs).

    Primary: Proportion of participants who remained in Low Disease Activity (LDA) (Disease Activity Score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR] <3.2) at Week 52.

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    End point title
    Proportion of participants who remained in Low Disease Activity (LDA) (Disease Activity Score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR] <3.2) at Week 52.
    End point description
    Proportion of participants who remained in LDA DAS28-ESR <3.2 at Week 52 is presented below.
    End point type
    Primary
    End point timeframe
    Baseline and Week 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: percentage of participants
        number (not applicable)
    43.6
    17.3
    Statistical analysis title
    Statistical analysis 1
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in Proportions
    Point estimate
    26.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.78
         upper limit
    35.81
    Notes
    [1] - Participants who flared in Period 2 are retreated and the data included used in efficacy analyses were carried forward from the last visit before retreatment.

    Secondary: Proportion of participants who remained in Remission at Week 52 (DAS28-ESR)

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    End point title
    Proportion of participants who remained in Remission at Week 52 (DAS28-ESR)
    End point description
    Proportion of participants who remained in Remission (DAS28-ESR <2.6) at Week 52.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: Percentage of participants
        number (not applicable)
    53.2
    29.5
    Statistical analysis title
    Statistical analysis 1
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.019
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    23.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.83
         upper limit
    40.61

    Secondary: Proportion of participants achieving LDA (DAS28-ESR and DAS28-C-reactive protein [CRP]) at each visit during Period 1

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    End point title
    Proportion of participants achieving LDA (DAS28-ESR and DAS28-C-reactive protein [CRP]) at each visit during Period 1
    End point description
    Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: Percentage of participants
    number (not applicable)
        DAS28-ESR Week 4 (N= 473)
    9.5
        DAS28-CRP Week 4 (N= 465)
    20.6
        DAS28-ESR Week 8 (N= 473)
    20.3
        DAS28-CRP Week 8 (N= 471)
    34.6
        DAS28-ESR Week 16 (N= 473)
    32.8
        DAS28-CRP Week 16 (N= 472)
    52.8
        DAS28-ESR Week 24 (N= 473)
    72.1
        DAS28-CRP Week 24 (N= 472)
    72.5
    No statistical analyses for this end point

    Secondary: Proportion of participants achieving LDA (DAS28-ESR and DAS28-CRP) at each visit during Period 2

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    End point title
    Proportion of participants achieving LDA (DAS28-ESR and DAS28-CRP) at each visit during Period 2
    End point description
    Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: Percentage of participants
    number (not applicable)
        DAS28-ESR Baseline (N= 163, 168)
    0
    0.6
        DAS28-CRP Baseline (N= 163, 168)
    0.6
    0
        DAS28-ESR Week 24 (N= 163, 168)
    100
    100
        DAS28-CRP Week 24 (N= 163, 168)
    87.7
    85.1
        DAS28-ESR Week 28 (N= 163, 168)
    62.6
    41.1
        DAS28-CRP Week 28 (N= 160, 166)
    74.4
    55.4
        DAS28-ESR Week 36 (N= 163, 168)
    55.2
    24.4
        DAS28-CRP Week 36 (N= 162, 167)
    69.1
    41.9
        DAS28-ESR Week 44 (N= 163, 168)
    51.5
    20.2
        DAS28-CRP Week 44 (N= 162, 167)
    69.1
    38.9
        DAS28-ESR Week 52 (N= 163, 168)
    43.6
    17.3
        DAS28-CRP Week 52 (N= 162, 167)
    64.2
    37.1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    DAS28-ESR Baseline
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.371
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.76
         upper limit
    0.57
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    DAS28-CRP Baseline
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.358
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.59
         upper limit
    1.81
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    DAS28-CRP Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.667
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    2.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.76
         upper limit
    9.98
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    DAS28-ESR Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    21.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.99
         upper limit
    32.02
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    DAS28-CRP Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.81
         upper limit
    29.1
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    DAS28-ESR Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    30.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    20.79
         upper limit
    40.83
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    DAS28-CRP Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    27.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.89
         upper limit
    37.54
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    DAS28-ESR Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    31.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    21.51
         upper limit
    41.08
    Statistical analysis title
    Statistical analysis 9
    Statistical analysis description
    DAS28-CRP Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    30.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    19.95
         upper limit
    40.47
    Statistical analysis title
    Statistical analysis 10
    Statistical analysis description
    DAS28-ESR Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    26.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.78
         upper limit
    35.81
    Statistical analysis title
    Statistical analysis 11
    Statistical analysis description
    DAS28-CRP Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    27.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.67
         upper limit
    37.47

    Secondary: Proportion of participants achieving remission (DAS28-ESR and DAS28-CRP) at each visit during Period 1

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    End point title
    Proportion of participants achieving remission (DAS28-ESR and DAS28-CRP) at each visit during Period 1
    End point description
    Proportion of participants who achieved remission (DAS28-ESR and DAS28-CRP at each visit during period 1 is presented below.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: Percentage of participants
    number (not applicable)
        DAS28-ESR Week 4 (N= 473)
    4
        DAS28-CRP Week 4 (N= 465)
    9
        DAS28-ESR Week 8 (N= 473)
    8.9
        DAS28-CRP Week 8 (N= 471)
    17.8
        DAS28-ESR Week 16 (N= 473)
    13.5
        DAS28-CRP Week 16 (N= 472)
    31.1
        DAS28-ESR Week 24 (N= 473)
    26.6
        DAS28-CRP Week 24 (N= 472)
    49.8
    No statistical analyses for this end point

    Secondary: Proportion of participants achieving remission (DAS28-ESR and DAS28-CRP) at each visit during Period 2

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    End point title
    Proportion of participants achieving remission (DAS28-ESR and DAS28-CRP) at each visit during Period 2
    End point description
    Proportion of participants who achieved LDA (DAS28-ESR and DAS28-CRP at each visit during period 2 is presented below.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: Percentage of participants
    number (not applicable)
        DAS28-ESR Baseline (N= 163, 168)
    0
    0
        DAS28-CRP Baseline (N= 163, 168)
    0
    0
        DAS28-ESR Week 24 (N= 163, 168)
    38
    36.3
        DAS28-CRP Week 24 (N= 163, 168)
    64.4
    63.1
        DAS28-ESR Week 28 (N= 163, 168)
    32.5
    20.2
        DAS28-CRP Week 28 (N= 160, 166)
    51.9
    34.9
        DAS28-ESR Week 36 (N= 163, 168)
    31.9
    17.3
        DAS28-CRP Week 36 (N= 162, 167)
    50
    25.1
        DAS28-ESR Week 44 (N= 163, 168)
    30.7
    11.9
        DAS28-CRP Week 44 (N= 162, 167)
    51.9
    21
        DAS28-ESR Week 52 (N= 163, 168)
    33.7
    13.1
        DAS28-CRP Week 52 (N= 162, 167)
    46.9
    19.8
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    DAS28-CRP Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.774
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.03
         upper limit
    11.68
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    DAS28-ESR Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.034
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    12.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.86
         upper limit
    21.69
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    DAS28-CRP Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.02
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    16.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.33
         upper limit
    27.54
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    DAS28-ESR Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.007
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    14.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.48
         upper limit
    23.8
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    DAS28-CRP Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    24.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    14.72
         upper limit
    34.98
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    DAS28-ESR Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    18.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.16
         upper limit
    27.38
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    DAS28-CRP Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    30.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    21.03
         upper limit
    40.76
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    DAS28-ESR Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    20.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.78
         upper limit
    29.52
    Statistical analysis title
    Statistical analysis 9
    Statistical analysis description
    DAS28-CRP Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    27.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    17.38
         upper limit
    36.93

    Secondary: Change from Baseline in DAS28-CRP and DAS28-ESR in Period 1

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    End point title
    Change from Baseline in DAS28-CRP and DAS28-ESR in Period 1
    End point description
    The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: units on a scale
    arithmetic mean (standard deviation)
        DAS28-ESR Week 4 (N= 473)
    -1.61 ± 1.08
        DAS28-CRP Week 4 (N= 465)
    -1.61 ± 1.05
        DAS28-ESR Week 8 (N= 473)
    -2.14 ± 1.18
        DAS28-CRP Week 8 (N= 471)
    -2.09 ± 1.14
        DAS28-ESR Week 16 (N= 473)
    -2.62 ± 1.26
        DAS28-CRP Week 16 (N= 472)
    -2.54 ± 1.21
        DAS28-ESR Week 24 (N= 473)
    -3.23 ± 1.35
        DAS28-CRP Week 24 (N= 472)
    -2.95 ± 1.27
    No statistical analyses for this end point

    Secondary: Change from Baseline in DAS28-CRP and DAS28-ESR in Period 2

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    End point title
    Change from Baseline in DAS28-CRP and DAS28-ESR in Period 2
    End point description
    The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 2. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: units on a scale
    arithmetic mean (standard deviation)
        DAS28-ESR Week 24 (N= 163, 168)
    -3.79 ± 1.04
    -3.7 ± 0.99
        DAS28-CRP Week 24 (N= 163, 168)
    -3.36 ± 1.03
    -3.32 ± 1.05
        DAS28-ESR Week 28 (N= 163, 168)
    -3.35 ± 1.31
    -2.73 ± 1.43
        DAS28-CRP Week 28 (N= 160, 166)
    -3.06 ± 1.26
    -2.53 ± 1.4
        DAS28-ESR Week 36 (N= 163, 168)
    -3.2 ± 1.4
    -2.4 ± 1.49
        DAS28-CRP Week 36 (N= 162, 167)
    -2.97 ± 1.35
    -2.27 ± 1.48
        DAS28-ESR Week 44 (N= 163, 168)
    -3.15 ± 1.36
    -2.31 ± 1.49
        DAS28-CRP Week 44 (N= 162, 167)
    -2.95 ± 1.35
    -2.19 ± 1.5
        DAS28-ESR Week 52 (N= 163, 168)
    -3.08 ± 1.4
    -2.28 ± 1.46
        DAS28-CRP Week 52 (N= 162, 167)
    -2.92 ± 1.36
    -2.16 ± 1.45
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    DAS28-ESR Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.73
         upper limit
    -0.2
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    DAS28-CRP Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.006
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.61
         upper limit
    -0.11
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    DAS28-ESR Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.68
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.96
         upper limit
    -0.39
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    DAS28-CRP Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.55
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.82
         upper limit
    -0.28
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    DAS28-ESR Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.03
         upper limit
    -0.46
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    DAS28-CRP Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.92
         upper limit
    -0.37
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    DAS28-ESR Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.98
         upper limit
    -0.4
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    DAS28-CRP Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.91
         upper limit
    -0.36

    Secondary: Time-to-flare during Period 2, based on the protocol criteria

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    End point title
    Time-to-flare during Period 2, based on the protocol criteria
    End point description
    Flare is defined as the criteria of loss of LDA plus ≥0.6 unit worsening in DAS28 score during period 2.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: Percentage of participants
        number (not applicable)
    52.1
    79.8
    Statistical analysis title
    Statistical analysis 1
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval

    Secondary: Proportion of participants achieving European League Against Rheumatism (EULAR) good and or moderate responses (by both DAS28-ESR and DAS28-CRP scores) at each visit during Period 1.

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    End point title
    Proportion of participants achieving European League Against Rheumatism (EULAR) good and or moderate responses (by both DAS28-ESR and DAS28-CRP scores) at each visit during Period 1.
    End point description
    EULAR response is based on DAS28-ESR scores. The following good and moderate response is defined based on DAS28-ESR at endpoint (DAS28-ESR improvement at from Baseline in parenthesis): ≤3.2 units (>1.2 units) is good response; ≤3.2 units (0.6-1.2 units) are moderate response; ≤3.2 units (≤0.6 units) are no response.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: Percentage of participants
    number (not applicable)
        Good Response: DAS28-ESR Week 4 (N= 473)
    9.5
        Good Response: DAS28-CRP Week 4 (N= 465)
    18.9
        Good Response: DAS28-ESR Week 8 (N= 473)
    19.5
        Good Response: DAS28-CRP Week 8 (N= 471)
    33.5
        Good Response: DAS28-ESR Week 16 (N= 473)
    32.3
        Good Response: DAS28-CRP Week 16 (N= 472)
    51.9
        Good Response: DAS28-ESR Week 24 (N= 473)
    71.5
        Good Response: DAS28-CRP Week 24 (N= 472)
    71.4
        Moderate Response: DAS28-ESR Week 4 (N= 473)
    69.1
        Moderate Response: DAS28-CRP Week 4 (N= 465)
    79.8
        Moderate Response: DAS28-ESR Week 8 (N= 473)
    86.9
        Moderate Response: DAS28-CRP Week 8 (N= 471)
    87.5
        Moderate Response: DAS28-ESR Week 16 (N= 473)
    92
        Moderate Response: DAS28-CRP Week 16 (N= 472)
    92.8
        Moderate Response: DAS28-ESR Week 24 (N= 473)
    94.1
        Moderate Response: DAS28-CRP Week 24 (N= 472)
    95.1
    No statistical analyses for this end point

    Secondary: Proportion of participants achieving EULAR good and or moderate responses (by both DAS28-ESR and DAS28-CRP scores) at each visit during Period 2.

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    End point title
    Proportion of participants achieving EULAR good and or moderate responses (by both DAS28-ESR and DAS28-CRP scores) at each visit during Period 2.
    End point description
    EULAR response is based on DAS28-ESR scores. The following good and moderate response is defined based on DAS28-ESR at endpoint (DAS28-ESR improvement at from Baseline in parenthesis): ≤3.2 units (>1.2 units) is good response; ≤3.2 units (0.6-1.2 units) are moderate response; ≤3.2 units (≤0.6 units) are no response.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: Percentage of participants
    number (not applicable)
        Good Response: DAS28-ESR Week 24 (N= 163, 168)
    99.4
    99.4
        Good Response: DAS28-CRP Week 24 (N= 163, 168)
    86.5
    85.1
        Good Response: DAS28-ESR Week 28 (N= 163, 168)
    62.6
    41.1
        Good Response: DAS28-CRP Week 28 (N= 160, 166)
    73.1
    54.8
        Good Response: DAS28-ESR Week 36 (N= 163, 168)
    55.2
    23.8
        Good Response: DAS28-CRP Week 36 (N= 162, 167)
    67.9
    40.7
        Good Response: DAS28-ESR Week 44 (N= 163, 168)
    50.9
    19.6
        Good Response: DAS28-CRP Week 44 (N= 162, 167)
    68.5
    37.7
        Good Response: DAS28-ESR Week 52 (N= 163, 168)
    42.9
    16.7
        Good Response: DAS28-CRP Week 52 (N= 162, 167)
    63
    35.9
        Moderate Response: DAS28-ESR Week 24 (N= 163,168)
    100
    100
        Moderate Response: DAS28-CRP Week 24 (N= 163,168)
    100
    100
        Moderate Response: DAS28-ESR Week 28 (N= 163,168)
    95.7
    87.5
        Moderate Response: DAS28-CRP Week 28 (N= 160,166)
    96.9
    90.4
        Moderate Response: DAS28-ESR Week 36 (N= 163,168)
    93.9
    83.9
        Moderate Response: DAS28-CRP Week 36 (N= 162,167)
    94.4
    85.6
        Moderate Response: DAS28-ESR Week 44 (N= 163,168)
    93.3
    81.5
        Moderate Response: DAS28-CRP Week 44 (N= 162,167)
    95.1
    84.4
        Moderate Response: DAS28-ESR Week 52 (N= 163,168)
    93.3
    82.1
        Moderate Response: DAS28-CRP Week 52 (N= 162,167)
    95.7
    84.4
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Good Response: DAS28-CRP Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.961
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.13
         upper limit
    8.9
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Good Response: DAS28-ESR Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    21.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.99
         upper limit
    32.02
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Good Response: DAS28-CRP Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.007
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    18.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.08
         upper limit
    28.53
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    Good Response: DAS28-ESR Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    31.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    21.42
         upper limit
    41.39
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    Good Response: DAS28-CRP Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    27.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.83
         upper limit
    37.54
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    Good Response: DAS28-ESR Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    31.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    21.53
         upper limit
    41.02
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    Good Response: DAS28-CRP Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    30.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    20.54
         upper limit
    41.05
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    Good Response: DAS28-ESR Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    26.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.82
         upper limit
    35.74
    Statistical analysis title
    Statistical analysis 9
    Statistical analysis description
    Good Response: DAS28-CRP Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.63
         upper limit
    37.44
    Statistical analysis title
    Statistical analysis 10
    Statistical analysis description
    Good Response: DAS28-ESR Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.766
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in Proportions
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.69
         upper limit
    1.65
    Statistical analysis title
    Statistical analysis 11
    Statistical analysis description
    Moderate Response: DAS28-ESR Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.091
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in Proportions
    Point estimate
    8.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.32
         upper limit
    14.1
    Statistical analysis title
    Statistical analysis 12
    Statistical analysis description
    Moderate Response: DAS28-CRP Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.227
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    6.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.28
         upper limit
    11.75
    Statistical analysis title
    Statistical analysis 13
    Statistical analysis description
    Moderate Response: DAS28-ESR Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.072
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    9.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.27
         upper limit
    16.6
    Statistical analysis title
    Statistical analysis 14
    Statistical analysis description
    Moderate Response: DAS28-CRP Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.108
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    8.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.43
         upper limit
    15.2
    Statistical analysis title
    Statistical analysis 15
    Statistical analysis description
    Moderate Response: DAS28-ESR Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.035
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    11.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.69
         upper limit
    18.72
    Statistical analysis title
    Statistical analysis 16
    Statistical analysis description
    Moderate Response: DAS28-ESR Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.03
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    10.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.2
         upper limit
    17.06
    Statistical analysis title
    Statistical analysis 17
    Statistical analysis description
    Moderate Response: DAS28-ESR Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.048
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    11.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.15
         upper limit
    18.06
    Statistical analysis title
    Statistical analysis 18
    Statistical analysis description
    Moderate Response: DAS28-CRP Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.016
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    11.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.92
         upper limit
    17.58

    Secondary: Proportion of participants achieving LDA or remission based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at each visit during Period 1.

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    End point title
    Proportion of participants achieving LDA or remission based on Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) at each visit during Period 1.
    End point description
    SDAI and CDAI are defined as: 1) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 1. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 1.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: Percentage of participants
    number (not applicable)
        CDAI: LDA Baseline (N= 478)
    0.4
        CDAI: LDA Week 4 (N= 473)
    16.7
        CDAI: LDA Week 8 (N= 473)
    33.8
        CDAI: LDA Week 16 (N= 473)
    53.9
        CDAI: LDA Week 24 (N= 473)
    75.7
        CDAI: Remission: Baseline (N= 478)
    0
        CDAI: Remission: Week 4 (N= 473)
    0.4
        CDAI: Remission: Week 8 (N= 473)
    1.7
        CDAI: Remission: Week 16 (N= 473)
    6.1
        CDAI: Remission: Week 24 (N= 473)
    10.8
        SDAI: LDA: Baseline (N= 478)
    0.2
        SDAI: LDA: Week 4 (N= 465)
    16.1
        SDAI: LDA: Week 8 (N= 471)
    32.5
        SDAI: LDA: Week 16 (N= 472)
    52.3
        SDAI: LDA: Week 24 (N= 472)
    72.5
        SDAI: Remission: Baseline (N= 478)
    0
        SDAI: Remission: Week 4 (N= 465)
    0.6
        SDAI: Remission: Week 8 (N= 471)
    1.9
        SDAI: Remission: Week 16 (N= 472)
    6.8
        SDAI: Remission: Week 24 (N= 472)
    14
    No statistical analyses for this end point

    Secondary: Proportion of participants achieving LDA or remission based on CDAI and SDAI at each visit during Period 2.

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    End point title
    Proportion of participants achieving LDA or remission based on CDAI and SDAI at each visit during Period 2.
    End point description
    SDAI and CDAI are defined as: 1) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 2.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: Percentage of participants
    number (not applicable)
        CDAI: LDA Baseline (N= 163, 168)
    0.6
    0
        CDAI: LDA Week 24 (N= 163, 168)
    93.9
    90.5
        CDAI: LDA Week 28 (N= 163, 168)
    76.1
    57.7
        CDAI: LDA Week 36 (N= 163, 168)
    71.2
    47
        CDAI: LDA Week 44 (N= 163, 168)
    70.6
    43.5
        CDAI: LDA Week 52 (N= 163, 168)
    66.9
    42.9
        CDAI: Remission: Baseline (N= 163, 168)
    0
    0
        CDAI: Remission: Week 24 (N= 163, 168)
    16.6
    14.3
        CDAI: Remission: Week 28 (N= 163, 168)
    14.7
    14.3
        CDAI: Remission: Week 36 (N= 163, 168)
    20.9
    12.5
        CDAI: Remission: Week 44 (N= 163, 168)
    22.1
    12.5
        CDAI: Remission: Week 52 (N= 163, 168)
    20.9
    11.9
        SDAI: LDA: Baseline (N= 163, 168)
    0.6
    0
        SDAI: LDA: Week 24 (N= 163, 168)
    90.2
    86.9
        SDAI: LDA: Week 28 (N= 160, 166)
    73.1
    55.4
        SDAI: LDA: Week 36 (N= 162, 167)
    69.8
    55.4
        SDAI: LDA: Week 44 (N= 162, 167)
    69.8
    42.5
        SDAI: LDA: Week 52 (N= 162, 167)
    66.7
    42.5
        SDAI: Remission: Baseline (N= 163, 168)
    0
    0
        SDAI: Remission: Week 24 (N= 163, 168)
    20.9
    17.9
        SDAI: Remission: Week 28 (N= 160, 166)
    16.3
    16.3
        SDAI: Remission: Week 36 (N= 162, 167)
    22.8
    12.6
        SDAI: Remission: Week 44 (N= 162, 167)
    22.2
    13.2
        SDAI: Remission: Week 52 (N= 162, 167)
    25.3
    13.2
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    CDAI: LDA Baseline
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.358
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.59
         upper limit
    1.81
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    CDAI: LDA: Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.341
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    3.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.38
         upper limit
    9.16
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    CDAI: LDA: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    18.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.4
         upper limit
    28.27
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    CDAI: LDA: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    24.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.88
         upper limit
    34.4
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    CDAI: LDA: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    27.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.85
         upper limit
    37.35
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    CDAI: LDA: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.61
         upper limit
    34.42
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    CDAI: Remission: Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.774
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    2.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.5
         upper limit
    10.06
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    CDAI: Remission: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.645
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.15
         upper limit
    8.03
    Statistical analysis title
    Statistical analysis 9
    Statistical analysis description
    CDAI: Remission: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.08
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    8.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.36
         upper limit
    16.35
    Statistical analysis title
    Statistical analysis 10
    Statistical analysis description
    CDAI: Remission: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.025
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    9.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.49
         upper limit
    17.68
    Statistical analysis title
    Statistical analysis 11
    Statistical analysis description
    CDAI: Remission: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.088
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.02
         upper limit
    16.88
    Statistical analysis title
    Statistical analysis 12
    Statistical analysis description
    SDAI: LDA: Baseline
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.358
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.59
         upper limit
    1.81
    Statistical analysis title
    Statistical analysis 13
    Statistical analysis description
    SDAI: LDA: Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.258
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    3.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.57
         upper limit
    10.13
    Statistical analysis title
    Statistical analysis 14
    Statistical analysis description
    SDAI: LDA: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.005
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    17.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.49
         upper limit
    27.92
    Statistical analysis title
    Statistical analysis 15
    Statistical analysis description
    SDAI: LDA: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    27.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    16.93
         upper limit
    37.55
    Statistical analysis title
    Statistical analysis 16
    Statistical analysis description
    SDAI: LDA: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    21.83
         upper limit
    42.23
    Statistical analysis title
    Statistical analysis 17
    Statistical analysis description
    SDAI: LDA: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    28.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    18
         upper limit
    38.69
    Statistical analysis title
    Statistical analysis 18
    Statistical analysis description
    SDAI: Remission: Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.672
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.51
         upper limit
    11.51
    Statistical analysis title
    Statistical analysis 19
    Statistical analysis description
    SDAI: Remission: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.556
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.03
         upper limit
    8
    Statistical analysis title
    Statistical analysis 20
    Statistical analysis description
    SDAI: Remission: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.022
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    10.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.07
         upper limit
    18.45
    Statistical analysis title
    Statistical analysis 21
    Statistical analysis description
    SDAI: Remission: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.047
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.85
         upper limit
    17.25
    Statistical analysis title
    Statistical analysis 22
    Statistical analysis description
    SDAI: Remission: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.031
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    12.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.7
         upper limit
    20.57

    Secondary: Change of CDAI and SDAI at each visit during Period 1.

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    End point title
    Change of CDAI and SDAI at each visit during Period 1.
    End point description
    SDAI and CDAI are defined as: 1) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 1. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 1.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: units on a scale
    arithmetic mean (standard deviation)
        CDAI Week 4 (N= 473)
    -16.78 ± 11.72
        CDAI Week 8 (N= 473)
    -21.69 ± 12.4
        CDAI Week 16 (N= 473)
    -25.77 ± 13.19
        CDAI Week 24 (N= 473)
    -29.25 ± 13.66
        SDAI Week 4 (N= 465)
    -18.19 ± 12.44
        SDAI Week 8 (N= 471)
    -23.06 ± 12.89
        SDAI Week 16 (N= 472)
    -27.17 ± 13.61
        SDAI Week 24 (N= 472)
    -30.56 ± 14.27
    No statistical analyses for this end point

    Secondary: Change of CDAI and SDAI at each visit during Period 2

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    End point title
    Change of CDAI and SDAI at each visit during Period 2
    End point description
    SDAI and CDAI are defined as: 1) SDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0-28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) + hs CRP (in mg/dL) in Period 2. 2) CDAI = DAS28 prorated Swollen Joint Count (0-28) + DAS28 prorated Tender Joint Count (0 28) + Physician Global Assessment of arthritis (0-10) + Subject Global Assessment of arthritis (0-10) in Period 2.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: units on a scale
    arithmetic mean (standard deviation)
        CDAI: Week 24 (N= 163, 168)
    -32.11 ± 12.06
    -32.23 ± 12.49
        CDAI: Week 28 (N= 163, 168)
    -29.62 ± 13.1
    -26.49 ± 15.87
        CDAI: Week 36 (N= 163, 168)
    -28.71 ± 13.56
    -24.33 ± 16.45
        CDAI: Week 44 (N= 163, 168)
    -28.63 ± 13.58
    -23.81 ± 16.48
        CDAI: Week 52 (N= 163, 168)
    -28.3 ± 13.61
    -23.52 ± 15.98
        SDAI: Week 24 (N= 163, 168)
    -33.61 ± 12.07
    -33.68 ± 13.03
        SDAI: Week 28 (N= 160, 166)
    -31.07 ± 13.58
    -27.58 ± 16.5
        SDAI: Week 36 (N= 162, 167)
    -30.2 ± 14.05
    -25.44 ± 17.17
        SDAI: Week 44 (N= 162, 167)
    -30.21 ± 14.14
    -24.85 ± 17.29
        SDAI: Week 52 (N= 162, 167)
    -29.86 ± 14.03
    -24.57 ± 16.79
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    CDAI: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.049
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.19
         upper limit
    -0.01
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    CDAI: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.005
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -3.38
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.72
         upper limit
    -1.05
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    CDAI: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -4.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.37
         upper limit
    -1.67
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    CDAI: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -4.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.36
         upper limit
    -1.68
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    SDAI: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.047
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.22
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.4
         upper limit
    -0.03
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    SDAI: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -3.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.97
         upper limit
    -1.12
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    SDAI: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -4.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.78
         upper limit
    -1.88
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    SDAI: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -4.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.7
         upper limit
    -1.84

    Secondary: Proportion of participants achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 joint counts) during Period 1 at each visit.

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    End point title
    Proportion of participants achieving American College of Rheumatology (ACR) ACR20, ACR50, ACR70 and ACR90 (by 66/68 joint counts) during Period 1 at each visit.
    End point description
    A 66 swollen and 68 tender joint count was used for calculating ACR responses. The ACR’s definition for calculating improvement in RA (ACR20) was calculated as a 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: subject and physician global assessments of arthritis, pain, disability, and an acute phase reactant. Similarly, ACR50, ACR70 and ACR90 were calculated with the respective percent improvement. This efficacy measurement was made at every study visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: percentage of participants
    number (not applicable)
        ACR 20: Week 4 (N= 469)
    58.6
        ACR 20: Week 8 (N= 469)
    73.1
        ACR 20: Week 16 (N= 469)
    83.6
        ACR 20: Week 24 (N= 469)
    87.8
        ACR 50: Week 4 (N= 469)
    19.8
        ACR 50: Week 8 (N= 469)
    35.8
        ACR 50: Week 16 (N= 469)
    55.2
        ACR 50: Week 24 (N= 469)
    72.5
        ACR 70: Week 4 (N= 469)
    4.3
        ACR 70: Week 8 (N= 469)
    11.1
        ACR 70: Week 16 (N= 469)
    23.7
        ACR 70: Week 24 (N= 469)
    39.4
        ACR 90: Week 4 (N= 469)
    0
        ACR 90: Week 8 (N= 469)
    0.4
        ACR 90: Week 16 (N= 469)
    1.5
        ACR 90: Week 24 (N= 469)
    5.8
    No statistical analyses for this end point

    Secondary: Proportion of participants achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 joint counts) during Period 2 at each visit.

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    End point title
    Proportion of participants achieving ACR20, ACR50, ACR70 and ACR90 (by 66/68 joint counts) during Period 2 at each visit.
    End point description
    A 66 swollen and 68 tender joint count was used for calculating ACR responses. The ACR’s definition for calculating improvement in RA (ACR20) was calculated as a 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: subject and physician global assessments of arthritis, pain, disability, and an acute phase reactant. Similarly, ACR50, ACR70 and ACR90 were calculated with the respective percent improvement. This efficacy measurement was made at every study visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: Percentage of participants
    number (not applicable)
        ACR 20: Week 24 (N= 161, 168)
    96.3
    96.4
        ACR 20: Week 28 (N= 161, 168)
    91.3
    81.5
        ACR 20: Week 36 (N= 161, 168)
    88.2
    76.8
        ACR 20: Week 44 (N= 161, 168)
    86.3
    76.2
        ACR 20: Week 52 (N= 161, 168)
    87
    76.2
        ACR 50: Week 24 (N= 161, 168)
    88.2
    85.7
        ACR 50: Week 28 (N= 161, 168)
    75.2
    63.7
        ACR 50: Week 36 (N= 161, 168)
    68.9
    51.8
        ACR 50: Week 44 (N= 161, 168)
    69.6
    50.6
        ACR 50: Week 52 (N= 161, 168)
    68.3
    50.6
        ACR 70: Week 24 (N= 161, 168)
    49.7
    52.4
        ACR 70: Week 28 (N= 161, 168)
    41
    33.9
        ACR 70: Week 36 (N= 161, 168)
    44.7
    27.4
        ACR 70: Week 44 (N= 161, 168)
    43.5
    25
        ACR 70: Week 52 (N= 161, 168)
    41
    25
        ACR 90: Week 24 (N= 161, 168)
    8.1
    8.3
        ACR 90: Week 28 (N= 161, 168)
    8.7
    5.4
        ACR 90: Week 36 (N= 161, 168)
    11.8
    5.4
        ACR 90: Week 44 (N= 161, 168)
    9.3
    4.8
        ACR 90: Week 52 (N= 161, 168)
    13
    7.1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    ACR 20: Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.742
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.21
         upper limit
    3.9
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    ACR 20: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.143
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    9.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.45
         upper limit
    17.06
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    ACR 20: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.111
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    11.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.31
         upper limit
    19.51
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    ACR 20: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.175
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    10.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.8
         upper limit
    18.49
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    ACR 20: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.088
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    10.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.49
         upper limit
    19.05
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    ACR 50: Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.584
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    2.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.78
         upper limit
    9.75
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    ACR 50: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.226
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    11.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.59
         upper limit
    21.34
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    ACR 50: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.012
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    17.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.76
         upper limit
    27.56
    Statistical analysis title
    Statistical analysis 9
    Statistical analysis description
    ACR 50: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.006
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.59
         upper limit
    29.35
    Statistical analysis title
    Statistical analysis 10
    Statistical analysis description
    ACR 50: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.014
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in Proportions
    Point estimate
    17.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.3
         upper limit
    28.16
    Statistical analysis title
    Statistical analysis 11
    Statistical analysis description
    ACR 70: Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.702
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in Proportions
    Point estimate
    -2.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.49
         upper limit
    8.11
    Statistical analysis title
    Statistical analysis 12
    Statistical analysis description
    ACR 70: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.378
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    7.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.37
         upper limit
    17.5
    Statistical analysis title
    Statistical analysis 13
    Statistical analysis description
    ACR 70: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    17.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.12
         upper limit
    27.56
    Statistical analysis title
    Statistical analysis 14
    Statistical analysis description
    ACR 70: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    18.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.4
         upper limit
    28.55
    Statistical analysis title
    Statistical analysis 15
    Statistical analysis description
    ACR 70: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.005
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.96
         upper limit
    26.02
    Statistical analysis title
    Statistical analysis 16
    Statistical analysis description
    ACR 90: Week 24
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.921
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.19
         upper limit
    5.67
    Statistical analysis title
    Statistical analysis 17
    Statistical analysis description
    ACR 90: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.41
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    3.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.19
         upper limit
    8.86
    Statistical analysis title
    Statistical analysis 18
    Statistical analysis description
    ACR 90: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.073
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    6.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.41
         upper limit
    12.48
    Statistical analysis title
    Statistical analysis 19
    Statistical analysis description
    ACR 90: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.219
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    4.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.97
         upper limit
    10.08
    Statistical analysis title
    Statistical analysis 20
    Statistical analysis description
    ACR 90: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.196
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in proportions
    Point estimate
    5.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    12.4

    Secondary: Change in the tender and swollen joint counts at each visit during Period 1 (using 28 joint count as well as 66/68 joint counts).

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    End point title
    Change in the tender and swollen joint counts at each visit during Period 1 (using 28 joint count as well as 66/68 joint counts).
    End point description
    A total of 66 swollen and 68 tender joints were assessed for tenderness/pain and swelling by the same qualified personnel (when possible) at each visit. For ACR responses, a 66/68 joint count was used. For DAS28, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) calculations, the 28 joint count was used, which included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: Percentage of participants
    arithmetic mean (standard deviation)
        28 Tender Joint Count: Week 4
    -6.49 ± 6.07
        28 Tender Joint Count: Week 8
    -8.59 ± 6.32
        28 Tender Joint Count: Week 16
    -10.12 ± 6.82
        28 Tender Joint Count: Week 24
    -11.5 ± 6.79
        28 Swollen Joint Count: Week 4
    -5.52 ± 5.02
        28 Swollen Joint Count: Week 8
    -7.04 ± 5.36
        28 Swollen Joint Count: Week 16
    -8.21 ± 5.44
        28 Swollen Joint Count: Week 24
    -9.01 ± 5.65
        68 Tender Joint Count: Week 4
    -9.71 ± 10
        68 Tender Joint Count: Week 8
    -13.02 ± 10.95
        68 Tender Joint Count: Week 16
    -15.21 ± 11.9
        68 Tender Joint Count: Week 24
    -17.41 ± 12.72
        68 Swollen Joint Count: Week 4
    -7.12 ± 6.86
        68 Swollen Joint Count: Week 8
    -9.03 ± 7.54
        68 Swollen Joint Count: Week 16
    -10.49 ± 7.62
        68 Swollen Joint Count: Week 24
    -11.53 ± 8.65
    No statistical analyses for this end point

    Secondary: Change in the tender and swollen joint counts at each visit during Period 2 (using 28 joint count as well as 66/68 joint counts).

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    End point title
    Change in the tender and swollen joint counts at each visit during Period 2 (using 28 joint count as well as 66/68 joint counts).
    End point description
    A total of 66 swollen and 68 tender joints were assessed for tenderness/pain and swelling by the same qualified personnel (when possible) at each visit. For ACR responses, a 66/68 joint count was used. For DAS28, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) calculations, the 28 joint count was used, which included: shoulders, elbows, wrists, metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, and knees.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: units on a scale
    arithmetic mean (standard deviation)
        28 Tender Joint Count: Week 24
    -12.65 ± 6.25
    -12.35 ± 6.45
        28 Tender Joint Count: Week 28
    -11.69 ± 6.74
    -10.08 ± 7.84
        28 Tender Joint Count: Week 36
    -11.22 ± 6.91
    -9.23 ± 8.07
        28 Tender Joint Count: Week 44
    -11.19 ± 6.82
    -8.97 ± 8.01
        28 Tender Joint Count: Week 52
    -11.03 ± 6.81
    -8.78 ± 7.83
        28 Swollen Joint Count: Week 24
    -9.78 ± 5.16
    -9.98 ± 5.58
        28 Swollen Joint Count: Week 28
    -8.97 ± 5.27
    -8.7 ± 5.94
        28 Swollen Joint Count: Week 36
    -8.64 ± 5.51
    -8.16 ± 6.04
        28 Swollen Joint Count: Week 44
    -8.71 ± 5.52
    -8.03 ± 6.08
        28 Swollen Joint Count: Week 52
    -8.59 ± 5.42
    -7.98 ± 6.05
        68 Tender Joint Count: Week 24
    -18.31 ± 12.13
    -18.19 ± 12.03
        68 Tender Joint Count: Week 28
    -17.02 ± 12.48
    -15.2 ± 13.95
        68 Tender Joint Count: Week 36
    -17.27 ± 12.55
    -17.13 ± 14.28
        68 Tender Joint Count: Week 44
    -18.67 ± 12.9
    -18.82 ± 14.71
        68 Tender Joint Count: Week 52
    -17.88 ± 13.21
    -17.61 ± 12.57
        68 Swollen Joint Count: Week 24
    -12.09 ± 7.76
    -12.4 ± 8.45
        68 Swollen Joint Count: Week 28
    -11.23 ± 7.77
    -10.81 ± 8.66
        68 Swollen Joint Count: Week 36
    -11.26 ± 8.05
    -10.67 ± 8.59
        68 Swollen Joint Count: Week 44
    -12 ± 8.03
    -11.63 ± 8.58
        68 Swollen Joint Count: Week 52
    -11.98 ± 8.17
    -11.89 ± 8.91
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    28 Tender Joint Count: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.062
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.84
         upper limit
    0.05
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    28 Tender Joint Count: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.015
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.41
         upper limit
    -0.27
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    28 Tender Joint Count: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.72
         upper limit
    -0.57
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    28 Tender Joint Count: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.85
         upper limit
    -0.66
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    28 Swollen Joint Count: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.68
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.77
         upper limit
    0.5
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    28 Swollen Joint Count: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.437
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.04
         upper limit
    0.45
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    28 Swollen Joint Count: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.131
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.57
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.31
         upper limit
    0.17
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    28 Swollen Joint Count: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.199
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.48
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.22
         upper limit
    0.25
    Statistical analysis title
    Statistical analysis 9
    Statistical analysis description
    68 Tender Joint Count: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.115
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.6
         upper limit
    0.28
    Statistical analysis title
    Statistical analysis 10
    Statistical analysis description
    68 Tender Joint Count: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.017
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.42
         upper limit
    -0.35
    Statistical analysis title
    Statistical analysis 11
    Statistical analysis description
    68 Tender Joint Count: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.91
         upper limit
    -0.76
    Statistical analysis title
    Statistical analysis 12
    Statistical analysis description
    68 Tender Joint Count: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.19
         upper limit
    -0.97
    Statistical analysis title
    Statistical analysis 13
    Statistical analysis description
    68 Swollen Joint Count: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.368
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.13
         upper limit
    0.42
    Statistical analysis title
    Statistical analysis 14
    Statistical analysis description
    68 Swollen Joint Count: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.208
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.57
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.46
         upper limit
    0.32
    Statistical analysis title
    Statistical analysis 15
    Statistical analysis description
    68 Swollen Joint Count: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.064
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.73
         upper limit
    0.05
    Statistical analysis title
    Statistical analysis 16
    Statistical analysis description
    68 Swollen Joint Count: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.081
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.66
         upper limit
    0.1

    Secondary: Change in the Physician Global Assessment of arthritis at each visit during Period 1

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    End point title
    Change in the Physician Global Assessment of arthritis at each visit during Period 1
    End point description
    The investigator estimated the subject’s overall disease activity over the last 2 to 3 days (independent of the Subject Global Assessment of arthritis) using a scale between 0 (no disease activity) and 10 (extreme disease activity) and marking one number with an ‘X’.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 4 (N= 473)
    -2.6 ± 1.78
        Week 8 (N= 473)
    -3.46 ± 1.9
        Week 16 (N= 473)
    -4.12 ± 1.96
        Week 24 (N= 473)
    -4.79 ± 2.02
    No statistical analyses for this end point

    Secondary: Change in the Physician Global Assessment of arthritis at each visit during Period 2

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    End point title
    Change in the Physician Global Assessment of arthritis at each visit during Period 2
    End point description
    The investigator estimated the subject’s overall disease activity over the last 2 to 3 days (independent of the Subject Global Assessment of arthritis) using a scale between 0 (no disease activity) and 10 (extreme disease activity) and marking one number with an ‘X’.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 24
    -5.28 ± 1.56
    -5.26 ± 1.78
        Week 28
    -4.93 ± 1.78
    -4.23 ± 2.43
        Week 36
    -4.83 ± 1.86
    -3.89 ± 2.48
        Week 44
    -4.82 ± 2.02
    -3.79 ± 2.53
        Week 52
    -4.77 ± 2.03
    -3.74 ± 2.43
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.005
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.53
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.9
         upper limit
    -0.16
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.18
         upper limit
    -0.38
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.35
         upper limit
    -0.54
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.33
         upper limit
    -0.53

    Secondary: Change in the Subject Global Assessment of arthritis in Period 1

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    End point title
    Change in the Subject Global Assessment of arthritis in Period 1
    End point description
    Subjects assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an ‘X’.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 4 (N= 473)
    -2.18 ± 2.21
        Week 8 (N= 473)
    -2.6 ± 2.34
        Week 16 (N= 473)
    -3.32 ± 2.44
        Week 24 (N= 473)
    -3.97 ± 2.6
    No statistical analyses for this end point

    Secondary: Change in the Subject Global Assessment of arthritis in Period 2

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    End point title
    Change in the Subject Global Assessment of arthritis in Period 2
    End point description
    Subjects assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an ‘X’.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 24
    -4.39 ± 2.43
    -4.64 ± 2.16
        Week 28
    -4.03 ± 2.7
    -3.48 ± 2.94
        Week 36
    -4.02 ± 2.71
    -3.05 ± 2.94
        Week 44
    -3.92 ± 2.79
    -3.02 ± 2.91
        Week 52
    -3.91 ± 2.84
    -3.02 ± 2.91
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.048
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    -0.01
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.44
         upper limit
    -0.43
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.83
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.33
         upper limit
    -0.33
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.33
         upper limit
    -0.31

    Secondary: Change in morning stiffness (measured in minutes) at each visit during Period 1

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    End point title
    Change in morning stiffness (measured in minutes) at each visit during Period 1
    End point description
    Morning stiffness was defined as stiffness in and around the joints, lasting at least 1 hour before maximal improvement. Participants assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an ‘X’.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: minutes
    arithmetic mean (standard deviation)
        Week 4 (N= 467)
    -78.56 ± 143.68
        Week 8 (N= 467)
    -90.58 ± 147.42
        Week 16 (N= 467)
    -102.25 ± 158.76
        Week 24 (N= 467)
    -109.32 ± 183.15
    No statistical analyses for this end point

    Secondary: Change in morning stiffness (measured in minutes) at each visit during Period 2

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    End point title
    Change in morning stiffness (measured in minutes) at each visit during Period 2
    End point description
    Morning stiffness was defined as stiffness in and around the joints, lasting at least 1 hour before maximal improvement. Participants assessed their overall disease activity over the last 2 to 3 days using a scale between 0 (no disease activity) and 10 (extreme disease activity), which corresponded to the magnitude of their pain) and marked one number with an ‘X’.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 24 (N= 163, 166)
    -118.3 ± 171.15
    -121.93 ± 186.17
        Week 28 (N= 163, 166)
    -134.42 ± 224.7
    -109.57 ± 163.79
        Week 36 (N= 163, 166)
    -132.05 ± 224.86
    -104.4 ± 164.13
        Week 44 (N= 163, 166)
    -129.86 ± 223.78
    -103.14 ± 162.65
        Week 52 (N= 163, 166)
    -129.49 ± 223.68
    -100.31 ± 153.62
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.033
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -14.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -27.07
         upper limit
    -1.16
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.013
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -17.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -30.39
         upper limit
    -3.68
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.019
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -16.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -30.35
         upper limit
    -2.73
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.007
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -19.66
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -33.78
         upper limit
    -5.54

    Secondary: Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at each visit during Period 1

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    End point title
    Change in the Subject General Health Visual Analog Scale (VAS) and Pain VAS at each visit during Period 1
    End point description
    Participants were asked to answer the question “In general how would you rate your health over the last 2 3 weeks?” by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: units on a scale
    arithmetic mean (standard deviation)
        General Health VAS: Week 4 (N= 473)
    -20.2 ± 22.22
        General Health VAS: Week 8 (N= 473)
    -25.17 ± 24.59
        General Health VAS: Week 16 (N= 473)
    -32.54 ± 24.89
        General Health VAS: Week 24 (N= 473)
    -40.67 ± 26.28
        Pain VAS: Week 4 (N= 473)
    -24.07 ± 22.56
        Pain VAS: Week 8 (N= 473)
    -28.55 ± 24.08
        Pain VAS: Week 16 (N= 473)
    -35.2 ± 24.81
        Pain VAS: Week 24 (N= 473)
    -42.49 ± 26.05
    No statistical analyses for this end point

    Secondary: Change in the Subject General Health VAS and Pain VAS at each visit during Period 2

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    End point title
    Change in the Subject General Health VAS and Pain VAS at each visit during Period 2
    End point description
    Participants were asked to answer the question “In general how would you rate your health over the last 2 3 weeks?” by marking a vertical line at the appropriate position through the 100 mm VAS. The length on the line was measured from the left (in mm). For Pain VAS, participants assessed the severity of their arthritis pain during the last 2 to 3 days using a 100 mm VAS by marking a vertical line at the appropriate position on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: units on a scale
    arithmetic mean (standard deviation)
        General Health VAS: Week 24
    -46.66 ± 24.72
    -47.53 ± 20.21
        General Health VAS: Week 28
    -41.31 ± 27.01
    -34.95 ± 28.95
        General Health VAS: Week 36
    -39.84 ± 26.56
    -30.74 ± 29.79
        General Health VAS: Week 44
    -39.82 ± 27.61
    -30.1 ± 29.88
        General Health VAS: Week 52
    -39.81 ± 28.16
    -29.67 ± 29.21
        Pain VAS: Week 24
    -46.61 ± 24.33
    -49.69 ± 20.64
        Pain VAS: Week 28
    -43.3 ± 36.34
    -38.17 ± 29.24
        Pain VAS: Week 36
    -41.42 ± 27.01
    -34 ± 30.3
        Pain VAS: Week 44
    -41.21 ± 28.01
    -33.07 ± 29.46
        Pain VAS: Week 52
    -40.95 ± 28.61
    -32.91 ± 29.26
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    General Health VAS: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.078
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -4.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.91
         upper limit
    0.48
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    General Health VAS: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -7.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.49
         upper limit
    -2.59
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    General Health VAS: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -8.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.2
         upper limit
    -3.18
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    General Health VAS: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -8.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.64
         upper limit
    -3.55
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    Pain VAS: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.017
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -5.91
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.75
         upper limit
    -1.06
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    Pain VAS: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -8.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.85
         upper limit
    -3.34
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    Pain VAS: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -9.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.72
         upper limit
    -4.26
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    Pain VAS: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -9.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.6
         upper limit
    -3.99

    Secondary: Change in CRP and ESR at each visit during Period 1

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    End point title
    Change in CRP and ESR at each visit during Period 1
    End point description
    The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 16 and 24
    End point values
    Open-Label Treatment
    Number of subjects analysed
    478
    Units: units on a scale
    arithmetic mean (standard deviation)
        CRP: Week 4 (N= 465)
    -14.07 ± 25.3
        CRP: Week 8 (N= 471)
    -14.43 ± 23.51
        CRP: Week 16 (N= 472)
    -14.71 ± 27.32
        CRP: Week 24 (N= 472)
    -14.51 ± 27.64
        ESR: Week 4 (N= 473)
    -17.32 ± 19.44
        ESR: Week 8 (N= 473)
    -19.28 ± 21.62
        ESR: Week 16 (N= 473)
    -21.1 ± 24.2
        ESR: Week 24 (N= 473)
    -26.77 ± 26.19
    No statistical analyses for this end point

    Secondary: Change in CRP and ESR at each visit during Period 2

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    End point title
    Change in CRP and ESR at each visit during Period 2
    End point description
    The DAS assessment is a derived measurement with differential weight given to each component. The DAS28-ESR and DAS28-CRP was calculated at every visit within the clinical database in period 1. The components of the DAS28 ESR score assessment are: Tender/ Painful Joint Count (28), Swollen Joint Count (28); ESR, Subject General Health VAS assessment. The components of the DAS28 CRP score assessment were: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement was made at every study visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 28, 36, 44 and 52
    End point values
    Etanercept Placebo
    Number of subjects analysed
    163
    168
    Units: units on a scale
    arithmetic mean (standard deviation)
        CRP: Week 24 (N= 161, 168)
    -16.92 ± 28.64
    -14.47 ± 21.59
        CRP: Week 28 (N= 160, 166)
    -15.94 ± 28.52
    -8.89 ± 25.46
        CRP: Week 36 (N= 162, 167)
    -15.56 ± 31.36
    -7.45 ± 25.55
        CRP: Week 44 (N= 162, 167)
    -16.47 ± 30.09
    -6.72 ± 26.32
        CRP: Week 52 (N= 162, 167)
    -16.29 ± 30.74
    -7.07 ± 26.76
        ESR: Week 24 (N= 163, 168)
    -31.52 ± 22.55
    -31.02 ± 24.24
        ESR: Week 28 (N= 163, 168)
    -26.96 ± 23.04
    -20.28 ± 23.68
        ESR: Week 36 (N= 163, 168)
    -26.1 ± 24.17
    -16.94 ± 23.08
        ESR: Week 44 (N= 163, 168)
    -24.39 ± 22.99
    -16.14 ± 23.1
        ESR: Week 52 (N= 163, 168)
    -23.56 ± 21.88
    -16.27 ± 22.65
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    CRP: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.014
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -5.22
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.39
         upper limit
    -1.05
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    CRP: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.011
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -6.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.09
         upper limit
    -1.46
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    CRP: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -7.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.06
         upper limit
    -3.44
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    CRP: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -7.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.48
         upper limit
    -2.85
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    ESR: Week 28
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -5.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.23
         upper limit
    -2.49
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    ESR: Week 36
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -8.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.33
         upper limit
    -5.05
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    ESR: Week 44
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -7.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.38
         upper limit
    -3.8
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    ESR: Week 52
    Comparison groups
    Etanercept v Placebo
    Number of subjects included in analysis
    331
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -6.32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.03
         upper limit
    -2.6

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from the signing of the informed consent to 28 days after the last dose of study medication through the last participant's visit.
    Adverse event reporting additional description
    The Open Label Safety Population is defined as all participants who had at least one dose of open label study drug during Period 1. The Double Blind Safety Population is defined as all randomized participants who had at least one dose of study drug during period 2.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Open-Label Treatment
    Reporting group description
    Participants in open-label treatment received ETN 50 mg with MTX (with or without other DMARDs).

    Reporting group title
    Etanercept
    Reporting group description
    Participants were randomized to receive ETN 50 mg QW with MTX (with or without other DMARDs).

    Reporting group title
    Placebo
    Reporting group description
    Participants were randomized to receive PBO 50 mg QW + MTX (with or without DMARDs).

    Serious adverse events
    Open-Label Treatment Etanercept Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 489 (2.66%)
    0 / 167 (0.00%)
    7 / 176 (3.98%)
         number of deaths (all causes)
    1
    0
    0
         number of deaths resulting from adverse events
    1
    0
    0
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 489 (0.00%)
    0 / 167 (0.00%)
    1 / 176 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 489 (0.00%)
    0 / 167 (0.00%)
    1 / 176 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    0 / 489 (0.00%)
    0 / 167 (0.00%)
    1 / 176 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Sudden death
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    0 / 489 (0.00%)
    0 / 167 (0.00%)
    1 / 176 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    1 / 176 (0.57%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 489 (0.00%)
    0 / 167 (0.00%)
    1 / 176 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 489 (0.00%)
    0 / 167 (0.00%)
    1 / 176 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Extradural abscess
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salmonella sepsis
         subjects affected / exposed
    1 / 489 (0.20%)
    0 / 167 (0.00%)
    0 / 176 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Open-Label Treatment Etanercept Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    26 / 489 (5.32%)
    4 / 167 (2.40%)
    9 / 176 (5.11%)
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    26 / 489 (5.32%)
    4 / 167 (2.40%)
    9 / 176 (5.11%)
         occurrences all number
    28
    4
    9

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Jan 2012
    In the protocol amendment 1, Clarifications to the details of MTX treatment, MTX supply, and medication errors. Changes to planned analyses: Site 1033 in the crimea was terminated early due to the Russian-Ukraine conflict. Participant exclusion from the analysis population was described in Section 10.2.
    22 Mar 2013
    In the protocol amendment 2, Clarifications to the Schedule of Activities; QFT testing language; number of sites and countries; definitions of loss of LDA and achieving LDA DAS28 ESR scores; Arm B dosing frequency; language to allow for possible re screenings; contact for breaking the blind; MTX supplies; language for MTX formulation and packaging; personnel performing 66/68 joint assessment; witness consent; reportable information; pregnancy testing language and exposure during pregnancy; laboratory determinations (TB testing was to be handled by a centralized laboratory and hs CRP testing to be done); AE reporting and other reportable information; and publication of study results. Clarifications to inclusion and exclusion criteria. Added a section on the sponsor’s qualified medical personnel and a section on protocol specified SAEs; added occupational exposure to definition of AEs; updated the version of the OMERACT flare questionnaire; added language that MTX was to be considered an IP; added the storage condition of MTX; added language to clarify when liver function tests were not required as a routine procedure; and added language on latex in Appendix 9 of the protocol.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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