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    Clinical Trial Results:
    MULTICENTER, OPEN-LABEL (PART A) FOLLOWED BY A RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP, PLACEBO-CONTROLLED STUDY (PART B) TO EVALUATE MAINTENANCE OF REMISSION IN SUBJECTS WITH ACTIVE AXIAL SPONDYLOARTHRITIS (AXSPA) RECEIVING EITHER CERTOLIZUMAB PEGOL 200MG Q2W OR 200MG Q4W AS COMPARED TO PLACEBO

    Summary
    EudraCT number
    2015-000339-34
    Trial protocol
    HU   BE   CZ   DE   GB   ES   NL   FR   RO   PL   BG  
    Global end of trial date
    23 Apr 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    08 May 2020
    First version publication date
    08 May 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    AS0005
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02505542
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB BIOSCIENCES GmbH
    Sponsor organisation address
    Alfred-Nobel-Strasse 10, Monheim, Germany, 40789
    Public contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
    Scientific contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.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
    09 May 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Apr 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the percentage of subjects who do not experience a flare on CZP 200 mg Q2W (full dose) or 200 mg Q4W (half-dose) as compared to placebo (CZP withdrawal) during Part B
    Protection of trial subjects
    During the conduct of the study all study participants were closely monitored.
    Background therapy
    Background therapy as permitted and stated in the protocol.
    Evidence for comparator
    Not Applicable
    Actual start date of recruitment
    31 Jul 2015
    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
    Spain: 5
    Country: Number of subjects enrolled
    Taiwan: 34
    Country: Number of subjects enrolled
    Turkey: 41
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    United States: 33
    Country: Number of subjects enrolled
    Belgium: 25
    Country: Number of subjects enrolled
    Bulgaria: 59
    Country: Number of subjects enrolled
    Czech Republic: 214
    Country: Number of subjects enrolled
    France: 9
    Country: Number of subjects enrolled
    Germany: 40
    Country: Number of subjects enrolled
    Hungary: 46
    Country: Number of subjects enrolled
    Netherlands: 6
    Country: Number of subjects enrolled
    Poland: 184
    Country: Number of subjects enrolled
    Romania: 34
    Worldwide total number of subjects
    736
    EEA total number of subjects
    628
    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)
    736
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study started to enroll patients in July 2015 and concluded in April 2019.

    Pre-assignment
    Screening details
    The study included 2 parts: Part A with a Screening Period (up to 5 Weeks) and an Open-Label Period (Week 0 to Week 48) and Part B with a Double-Blind Period (Week 48 to Week 96) and a Safety Follow-Up Period (10 weeks after the last dose of study medication). Participant Flow refers to the Open-Label Set.

    Period 1
    Period 1 title
    Part A: Open-Label Period
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Certolizumab pegol Open-Label
    Arm description
    Participants in this arm received certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B.
    Arm type
    Experimental

    Investigational medicinal product name
    Certolizumab pegol
    Investigational medicinal product code
    CZP
    Other name
    Cimzia
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Certolizumab pegol (CZP) 400 mg or 200 mg were administered as subcutaneous (sc) injections every 2 weeks (Q2W) (full-dose) or every 4 weeks (Q4W) (half-dose). Suitable areas for administrations were the lateral abdominal wall and upper outer thigh. Study medication should have been administered with a minimum of 10 days between the CZP 200 mg Q2W administrations.

    Number of subjects in period 1
    Certolizumab pegol Open-Label
    Started
    736
    Completed
    659
    Not completed
    77
         Protocol deviation
    1
         Participant did not attend week 48 visit
    1
         Lack of efficacy
    5
         Non-compliance
    1
         Sponsor directive
    1
         Pregnancy
    2
         New medical history available
    1
         Adverse event, non-fatal
    31
         Screening failure (detected too late)
    1
         Medical monitor decision
    1
         Consent withdrawn by subject
    27
         Lost to follow-up
    5
    Period 2
    Period 2 title
    Completed Part A, did not enter Part B
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Certolizumab pegol Open-Label
    Arm description
    Participants in this arm received certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B.
    Arm type
    Experimental

    Investigational medicinal product name
    Certolizumab pegol
    Investigational medicinal product code
    CZP
    Other name
    Cimzia
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Certolizumab pegol (CZP) 400 mg or 200 mg were administered as subcutaneous (sc) injections every 2 weeks (Q2W) (full-dose) or every 4 weeks (Q4W) (half-dose). Suitable areas for administrations were the lateral abdominal wall and upper outer thigh. Study medication should have been administered with a minimum of 10 days between the CZP 200 mg Q2W administrations.

    Number of subjects in period 2
    Certolizumab pegol Open-Label
    Started
    659
    Completed
    313
    Not completed
    346
         The subject was not eligible for Part B
    341
         Lack of efficacy
    2
         Consent withdrawn by subject
    3
    Period 3
    Period 3 title
    Part B: Double-Blind Period
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Investigator, Carer, Assessor, Subject
    Blinding implementation details
    Subjects who flared were given escape treatment until the end of the study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo Double-Blind
    Arm description
    Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    PBO
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Matching Placebo was administered as subcutaneous (sc) injections every 2 weeks (Q2W) or to maintain the study blind.

    Arm title
    Certolizumab pegol 200 mg Q2W Double-Blind
    Arm description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
    Arm type
    Experimental

    Investigational medicinal product name
    Certolizumab pegol
    Investigational medicinal product code
    CZP
    Other name
    Cimzia
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Certolizumab pegol (CZP) 400 mg or 200 mg were administered as subcutaneous (sc) injections every 2 weeks (Q2W) (full-dose) or every 4 weeks (Q4W) (half-dose). Suitable areas for administrations were the lateral abdominal wall and upper outer thigh. Study medication should have been administered with a minimum of 10 days between the CZP 200 mg Q2W administrations.

    Arm title
    Certolizumab pegol 200 mg Q4W Double-Blind
    Arm description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards. At visits where CZP was not received, subjects received one injection of Placebo to maintain the study blind.
    Arm type
    Experimental

    Investigational medicinal product name
    Certolizumab pegol
    Investigational medicinal product code
    CZP
    Other name
    Cimzia
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Certolizumab pegol (CZP) 400 mg or 200 mg were administered as subcutaneous (sc) injections every 2 weeks (Q2W) (full-dose) or every 4 weeks (Q4W) (half-dose). Suitable areas for administrations were the lateral abdominal wall and upper outer thigh. Study medication should have been administered with a minimum of 10 days between the CZP 200 mg Q2W administrations.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    PBO
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Matching Placebo was administered as subcutaneous (sc) injections every 2 weeks (Q2W) or to maintain the study blind.

    Number of subjects in period 3
    Placebo Double-Blind Certolizumab pegol 200 mg Q2W Double-Blind Certolizumab pegol 200 mg Q4W Double-Blind
    Started
    104
    104
    105
    Started Escape Period
    73 [1]
    7 [2]
    15 [3]
    Completed
    92
    95
    98
    Not completed
    12
    9
    7
         Week 94 missed
    -
    1
    -
         Miscalculation
    1
    -
    -
         Patient was moved from the country
    -
    -
    1
         Lack of efficacy
    1
    -
    -
         Subject did not complete all visits
    1
    -
    -
         Adverse event, non-fatal
    -
    1
    3
         Consent withdrawn by subject
    8
    7
    2
         Lost to follow-up
    -
    -
    1
         Planning pregnancy
    1
    -
    -
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Number of participants at the milestones reflects those who experienced a flare during the Double-Blind Period and escaped to full-dose treatment until the end of that period or for at least 12 weeks, whichever is longer.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Number of participants at the milestones reflects those who experienced a flare during the Double-Blind Period and escaped to full-dose treatment until the end of that period or for at least 12 weeks, whichever is longer.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Number of participants at the milestones reflects those who experienced a flare during the Double-Blind Period and escaped to full-dose treatment until the end of that period or for at least 12 weeks, whichever is longer.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Certolizumab pegol Open-Label
    Reporting group description
    Participants in this arm received certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B.

    Reporting group values
    Certolizumab pegol Open-Label Total
    Number of subjects
    736 736
    Age categorical
    Units: Subjects
        <=18 years
    7 7
        Between 18 and 65 years
    729 729
        >=65 years
    0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    32.9 ± 7.0 -
    Gender categorical
    Units: Subjects
        Male
    514 514
        Female
    222 222

    End points

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    End points reporting groups
    Reporting group title
    Certolizumab pegol Open-Label
    Reporting group description
    Participants in this arm received certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B.
    Reporting group title
    Certolizumab pegol Open-Label
    Reporting group description
    Participants in this arm received certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B.
    Reporting group title
    Placebo Double-Blind
    Reporting group description
    Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.

    Reporting group title
    Certolizumab pegol 200 mg Q2W Double-Blind
    Reporting group description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.

    Reporting group title
    Certolizumab pegol 200 mg Q4W Double-Blind
    Reporting group description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards. At visits where CZP was not received, subjects received one injection of Placebo to maintain the study blind.

    Subject analysis set title
    Placebo Double-Blind (RS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards. Participants formed the Randomized Set (RS).

    Subject analysis set title
    Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards. Participants formed the RS.

    Subject analysis set title
    Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards. At visits where CZP was not received, subjects received one injection of Placebo to maintain the study blind. Participants formed the RS.

    Subject analysis set title
    Certolizumab pegol Open-Label (OLS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants in this arm received certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B. Participants formed the Open-Label Set (OLS).

    Subject analysis set title
    Placebo DB/CZP 200 mg Q2W Escape (FS)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants randomized to Placebo who met flare criteria received CZP 400 mg subcutaneous (sc) every 2 weeks (Q2W) for the first 3 visits after flare has been confirmed. After that, CZP 200 mg was given every 2 weeks in open-label fashion. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the Flared Set (FS).

    Subject analysis set title
    CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants randomized to CZP 200 mg Q2W who meet flare criteria received CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, participants received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the FS.

    Subject analysis set title
    CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants randomized to CZP 200 mg Q4W who meet flare criteria received CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, participants received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the FS.

    Subject analysis set title
    Certolizumab pegol Open-Label (SS) Wk 0-48
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants in this arm received certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B. Participants formed the Safety Set (SS).

    Subject analysis set title
    Placebo Double-Blind (SSB) Wk 48–96
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards. Participants formed the Safety Set Part B (SSB).

    Subject analysis set title
    Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards. Participants formed the SSB.

    Subject analysis set title
    Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards. At visits where CZP was not received, subjects received one injection of Placebo to maintain the study blind. Participants formed the SSB.

    Subject analysis set title
    Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants randomized to Placebo who met flare criteria received CZP 400 mg subcutaneous (sc) every 2 weeks (Q2W) for the first 3 visits after flare has been confirmed. After that, CZP 200 mg was given every 2 weeks in open-label fashion. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the Escape Therapy Set (ETS).

    Subject analysis set title
    CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants randomized to CZP 200 mg Q2W who meet flare criteria received CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, participants received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the ETS.

    Subject analysis set title
    CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants randomized to CZP 200 mg Q4W who meet flare criteria received CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, participants received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the ETS.

    Subject analysis set title
    Placebo Double-Blind (PKSB)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards. Participants formed the Pharmacokinetic Set B (PKSB).

    Subject analysis set title
    Certolizumab pegol 200 mg Q2W Double-Blind (PKSB)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards. Participants formed the PKSB.

    Subject analysis set title
    Certolizumab pegol 200 mg Q4W Double-Blind (PKSB)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards. At visits where CZP was not received, subjects received one injection of Placebo to maintain the study blind. Participants formed the PKSB.

    Primary: Percentage of participants in Part B who did not experienced a flare

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    End point title
    Percentage of participants in Part B who did not experienced a flare
    End point description
    A participant was considered to have experienced a flare if the participant had an Ankylosing spondylitis disease activity score (ASDAS) greater or equal to (≥) 2.1 at 2 consecutive visits or an ASDAS greater than (>) 3.5 at any visit during Part B up until Week 96. A participant qualified for Part B only if he achieved sustained remission after 48 weeks of Open-Label certolizumab pegol (CZP) treatment. Sustained remission was achieved when a participant had an ASDAS less than (<) 1.3 at Week 32 or Week 36 (if ASDAS < 1.3 at Week 32, it must have been < 2.1 at Week 36; if ASDAS < 2.1 at Week 32, it must have been < 1.3 at Week 36) and an ASDAS < 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods.
    End point type
    Primary
    End point timeframe
    From Week 48 to Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: percentage of participants
        number (confidence interval 95%)
    20.2 (13.0 to 29.2)
    83.7 (75.1 to 90.2)
    79.0 (70.0 to 86.4)
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Odds ratio (and corresponding p-value) resulted from a logistic regression model with factors for treatment, geographic region, and modified New York (mNY) classification for study participants who did not experience a flare. An odds ratio > 1 indicates a study participant on CZP was more likely not to experience a flare than a study participant on placebo. Penalized maximum likelihood approach was used for logistic regression.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [1]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    18.822
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.605
         upper limit
    38.864
    Notes
    [1] - A fixed sequence testing procedure was used whereby the second test (CZP 200 mg Q4W vs PBO) was interpreted as statistically significant only if the first test (CZP 200 mg Q2W vs PBO) was significant at the 0.05 level as well.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Odds ratio (and corresponding p-value) resulted from a logistic regression model with factors for treatment, geographic region, and modified New York (mNY) classification for study participants who did not experience a flare. An odds ratio > 1 indicates a study participant on CZP was more likely not to experience a flare than a study participant on placebo. Penalized maximum likelihood approach was used for logistic regression.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001 [2]
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    14.069
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.395
         upper limit
    27.955
    Notes
    [2] - A fixed sequence testing procedure was used whereby the second test (CZP 200 mg Q4W vs PBO) was interpreted as statistically significant only if the first test (CZP 200 mg Q2W vs PBO) was significant at the 0.05 level as well.

    Secondary: Percentage of participants achieving sustained remission at Week 48 in Part A

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    End point title
    Percentage of participants achieving sustained remission at Week 48 in Part A
    End point description
    Sustained remission was achieved when a participant had an ASDAS less than (<) 1.3 at Week 32 or Week 36 (if ASDAS < 1.3 at Week 32, it must have been < 2.1 at Week 36; if ASDAS < 2.1 at Week 32, it must have been < 1.3 at Week 36) and an ASDAS < 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    Certolizumab pegol Open-Label (OLS)
    Number of subjects analysed
    736
    Units: percentage of participants
        number (confidence interval 95%)
    43.9 (40.3 to 47.6)
    No statistical analyses for this end point

    Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 48 in Part A

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    End point title
    Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 48 in Part A
    End point description
    The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Disease activity was measured by categorical response variables: • ASDAS-Inactive Disease (ASDAS-ID): ASDAS < 1.3 • ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, < 2.1 • ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 • ASDAS-very High Disease activity (ASDAS-vHD): ASDAS > 3.5 Missing data were handled using last observation carried forward (LOCF) methods.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    Certolizumab pegol Open-Label (OLS)
    Number of subjects analysed
    736
    Units: percentage of participants
    number (not applicable)
        ASDAS-ID
    52.5
        ASDAS-MD
    22.8
        ASDAS-HD
    18.9
        ASDAS-vHD
    5.9
    No statistical analyses for this end point

    Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 48 in Part A

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    End point title
    Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 48 in Part A
    End point description
    The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). ASDAS improvement was measured by binary response variables: • ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline • ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    Certolizumab pegol Open-Label (OLS)
    Number of subjects analysed
    736
    Units: percentage of participants
    number (not applicable)
        ASDAS-CII
    76.6
        ASDAS-MI
    56.1
    No statistical analyses for this end point

    Secondary: Time to flare in Part B

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    End point title
    Time to flare in Part B
    End point description
    For those who met the criteria for flare (see primary efficacy variable), the time to flare was the length in days from randomization in Part B until the visit at which the criteria for flare were met. Participants who discontinued the study without meeting the criteria for flare were counted as experiencing a flare at the time of their last study visit. The time to flare was analyzed using Kaplan-Meier methods. If Kaplan-Meier Estimate was NA for all estimates then more than 75 % failed to meet the flare condition. Missing data were handled using non-response imputation (NRI) methods. Note: 999 was used as a placeholder for values that were not calculated since more than 75 % failed to meet the flare condition.
    End point type
    Secondary
    End point timeframe
    From Week 48 to Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: days
        median (inter-quartile range (Q1-Q3))
    113 (84 to 257)
    371 (371 to 371)
    999 (999 to 999)
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    P-values were from stratified log-rank test comparing the Certolizumab pegol 200 mg Q2W Double-Blind (RS) group with the Placebo Double-Blind (RS) group (Geographic region and modified New York (mNY) classification were used as stratification factors).
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    P-values were from stratified log-rank test comparing the Certolizumab pegol 200 mg Q4W Double-Blind (RS) group with the Placebo Double-Blind (RS) group (Geographic region and modified New York (mNY) classification were used as stratification factors).
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval

    Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 96 in Part B

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    End point title
    Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Week 96 in Part B
    End point description
    The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Disease activity was measured by categorical response variables: • ASDAS-Inactive Disease (ASDAS-ID): ASDAS < 1.3 • ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, < 2.1 • ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 • ASDAS-very High Disease activity (ASDAS-vHD): ASDAS > 3.5
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: percentage of participants
    number (not applicable)
        ASDAS-ID
    58.3
    86.2
    69.9
        ASDAS-MD
    25.0
    13.8
    22.9
        ASDAS-HD
    16.7
    0
    7.2
        ASDAS-vHD
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 96 in Part B

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    End point title
    Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Week 96 in Part B
    End point description
    The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). ASDAS improvement was measured by binary response variables: • ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline • ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: percentage of participants
    number (not applicable)
        ASDAS-CII
    21.2
    82.7
    75.2
        ASDAS-MI
    10.6
    67.3
    58.1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    17.94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.95
         upper limit
    35.961
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    11.385
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.952
         upper limit
    21.778
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    17.653
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.333
         upper limit
    37.399
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and modified New York (mNY) classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    11.863
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.67
         upper limit
    24.822

    Secondary: Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Week 96 in Part B

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    End point title
    Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Week 96 in Part B
    End point description
    The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Missing data were handled using non-response imputation (NRI) methods.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: percentage of participants
        number (not applicable)
    23.1
    85.6
    78.1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    20.205
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.851
         upper limit
    41.439
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    12.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.275
         upper limit
    23.218

    Secondary: Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Week 96 in Part B

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    End point title
    Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Week 96 in Part B
    End point description
    The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain. Missing data were handled using non-response imputation (NRI) methods.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: percentage of participants
        number (not applicable)
    21.2
    84.6
    73.3
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    20.891
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.21
         upper limit
    42.744
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    10.377
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.456
         upper limit
    19.738

    Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Week 96 in Part B

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    End point title
    Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Week 96 in Part B
    End point description
    The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP). Missing data were handled using non-response imputation (NRI) methods.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: percentage of participants
        number (not applicable)
    12.5
    70.2
    62.9
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    16.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.211
         upper limit
    34.785
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    12.072
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.954
         upper limit
    24.476

    Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Week 96 in Part B

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    End point title
    Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Week 96 in Part B
    End point description
    The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20. Missing data were handled using non-response imputation (NRI) methods.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: percentage of participants
        number (not applicable)
    17.3
    77.9
    70.5
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    17.082
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.561
         upper limit
    34.085
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    11.503
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.939
         upper limit
    22.278

    Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B

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    End point title
    Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B
    End point description
    The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as “below the limit of quantification” (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From Week 48 to Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: scores on a scale
        least squares mean (standard error)
    1.66 ± 0.110
    0.24 ± 0.077
    0.45 ± 0.077
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -1.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.66
         upper limit
    -1.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.126
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -1.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.45
         upper limit
    -0.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.126

    Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B

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    End point title
    Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B
    End point description
    The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From Week 48 to Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: scores on a scale
        least squares mean (standard error)
    3.02 ± 0.226
    0.56 ± 0.176
    0.78 ± 0.176
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -2.46
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.99
         upper limit
    -1.94
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.268
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -2.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.77
         upper limit
    -1.72
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.267

    Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B

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    End point title
    Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B
    End point description
    The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From Week 48 to Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: scores on a scale
        least squares mean (standard error)
    1.90 ± 0.233
    0.32 ± 0.198
    0.46 ± 0.205
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -1.57
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.04
         upper limit
    -1.11
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.238
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -1.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    -0.96
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.238

    Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B

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    End point title
    Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B
    End point description
    The BASMI is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From Week 48 to Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: scores on a scale
        least squares mean (standard error)
    0.21 ± 0.105
    0.00 ± 0.065
    -0.03 ± 0.068
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.074
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.42
         upper limit
    0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.112
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    An mixed model with repeated measures (MMRM) analysis on all observed post-baseline data with the following fixed-effect covariates was used: treatment, geographical region, mNY classification, Part B Baseline value, and visit as fixed-effect factors, as well as treatment group by visit interaction and Part B Baseline value by visit interaction.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.036
    Method
    Mixed models analysis
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.46
         upper limit
    -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.113

    Secondary: Percentage of participants with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response criteria response at Week 96 in Part B

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    End point title
    Percentage of participants with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response criteria response at Week 96 in Part B
    End point description
    The BASDAI50 response was defined as an improvement of at least 50 % in the BASDAI score relative to Baseline. Missing data were handled using non-response imputation (NRI) methods.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    104
    104
    105
    Units: percentage of participants
        number (not applicable)
    22.1
    83.7
    77.1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    18.308
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.084
         upper limit
    36.898
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    209
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    12.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.255
         upper limit
    23.098

    Secondary: Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Week 96 in Part B

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    End point title
    Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Week 96 in Part B
    End point description
    The SPARCC scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total Sacroiliac (SI) joint SPARCC score can range from 0 to 72 with higher scores indicating higher joint inflammation. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From Week 48 to Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    24
    79
    77
    Units: scores on a scale
        arithmetic mean (standard deviation)
    1.1 ± 3.6
    0.2 ± 2.4
    0.6 ± 3.8
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Only MRIs performed ± 2 weeks around the Week 96 or Early Withdrawal Visit were assigned to Week 96 or Early Withdrawal. Only results of the double-read assessments of the central MRI review were included. The analysis used the average of the scores from the 2 independent reviewers. Whenever an adjudication was present, the average score across all 3 reviewers was used. ANCOVA model with treatment, geographical region, mNY classification, and Part B Baseline as covariates.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.195
    Method
    ANCOVA
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.5
         upper limit
    0.51
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.76
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Only MRIs performed ± 2 weeks around the Week 96 or Early Withdrawal Visit were assigned to Week 96 or Early Withdrawal. Only results of the double-read assessments of the central MRI review were included. The analysis used the average of the scores from the 2 independent reviewers. Whenever an adjudication was present, the average score across all 3 reviewers was used. ANCOVA model with treatment, geographical region, mNY classification, and Part B Baseline as covariates.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.432
    Method
    ANCOVA
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.11
         upper limit
    0.91
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.76

    Secondary: Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for Disease activity (ASspIMRI-a) in the Berlin modification score at Week 96 in Part B

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    End point title
    Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for Disease activity (ASspIMRI-a) in the Berlin modification score at Week 96 in Part B
    End point description
    The Berlin modification of the ASspiMRI-a is a scoring system with a concentration on Short-Tau-Inversion Recovery (STIR) sequences without other fat saturation techniques. It quantifies changes in 23 Vertebral Units (VU) of the spine. Active inflammation was scored by grading the degree of bone marrow edema from 0 to 3 in 1 dimension on 1 or more consecutive slices that represent the highest level of inflammation in a particular VU. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From Week 48 to Week 96
    End point values
    Placebo Double-Blind (RS) Certolizumab pegol 200 mg Q2W Double-Blind (RS) Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects analysed
    24
    79
    78
    Units: scores on a scale
        arithmetic mean (standard deviation)
    0.4 ± 0.9
    0.0 ± 0.8
    0.0 ± 0.8
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Only MRIs performed ± 2 weeks around the Week 96 or Early Withdrawal Visit were assigned to Week 96 or Early Withdrawal. Only results of the double-read assessments of the central MRI review were included. The analysis used the average of the scores from the 2 independent reviewers. Whenever an adjudication was present, the average score across all 3 reviewers was used. ANCOVA model with treatment, geographical region, mNY classification, and Part B Baseline as covariates.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q2W Double-Blind (RS)
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.04
    Method
    ANCOVA
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.78
         upper limit
    -0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.19
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Only MRIs performed ± 2 weeks around the Week 96 or Early Withdrawal Visit were assigned to Week 96 or Early Withdrawal. Only results of the double-read assessments of the central MRI review were included. The analysis used the average of the scores from the 2 independent reviewers. Whenever an adjudication was present, the average score across all 3 reviewers was used. ANCOVA model with treatment, geographical region, mNY classification, and Part B Baseline as covariates.
    Comparison groups
    Placebo Double-Blind (RS) v Certolizumab pegol 200 mg Q4W Double-Blind (RS)
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.074
    Method
    ANCOVA
    Parameter type
    LS Mean Difference vs Placebo
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.73
         upper limit
    0.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.19

    Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) disease activity categories at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). Disease activity was measured by categorical response variables: • ASDAS-Inactive Disease (ASDAS-ID): ASDAS < 1.3 • ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, < 2.1 • ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5 • ASDAS-very High Disease activity (ASDAS-vHD): ASDAS > 3.5
    End point type
    Secondary
    End point timeframe
    Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    73
    7
    15
    Units: percentage of participants
    number (not applicable)
        ASDAS-ID
    63.4
    16.7
    60.0
        ASDAS-MD
    26.8
    50.0
    20.0
        ASDAS-HD
    8.5
    33.3
    20.0
        ASDAS-vHD
    1.4
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Percentage of participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) clinical improvement categories at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). ASDAS improvement was measured by binary response variables: • ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline • ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline
    End point type
    Secondary
    End point timeframe
    Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    73
    7
    15
    Units: percentage of participants
    number (not applicable)
        ASDAS-CII
    84.5
    16.7
    46.7
        ASDAS-MI
    49.3
    0
    13.3
    No statistical analyses for this end point

    Secondary: Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Percentage of participants with Axial SpondyloArthritis International Society 20 % response criteria (ASAS20) response at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The ASAS20 response was defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20% and an absolute worsening of at least 1 unit].
    End point type
    Secondary
    End point timeframe
    Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    73
    7
    15
    Units: percentage of participants
        number (not applicable)
    83.3
    50.0
    64.3
    No statistical analyses for this end point

    Secondary: Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Percentage of participants with Axial SpondyloArthritis International Society 40 % response criteria (ASAS40) response at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.
    End point type
    Secondary
    End point timeframe
    Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    73
    7
    15
    Units: percentage of participants
        number (not applicable)
    69.4
    16.7
    50.0
    No statistical analyses for this end point

    Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Percentage of participants with Axial SpondyloArthritis International Society (ASAS) 5/6 response criteria response at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).
    End point type
    Secondary
    End point timeframe
    Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    73
    7
    15
    Units: percentage of participants
        number (not applicable)
    60.6
    16.7
    7.1
    No statistical analyses for this end point

    Secondary: Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Percentage of participants with Axial SpondyloArthritis International Society (ASAS) partial remission (PR) response criteria response at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.
    End point type
    Secondary
    End point timeframe
    Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    73
    7
    15
    Units: percentage of participants
        number (not applicable)
    66.7
    16.7
    50.0
    No statistical analyses for this end point

    Secondary: Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Change from Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient’s Global Assessment of Disease Activity) 0.073 x Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as “below the limit of quantification” (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From time of flare to Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    71
    6
    15
    Units: scores on a scale
        arithmetic mean (standard deviation)
    -2.18 ± 1.13
    -0.56 ± 0.64
    -0.83 ± 0.94
    No statistical analyses for this end point

    Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From time of flare to Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    72
    6
    15
    Units: scores on a scale
        arithmetic mean (standard deviation)
    -3.75 ± 2.52
    -1.55 ± 1.05
    -2.29 ± 2.35
    No statistical analyses for this end point

    Secondary: Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From time of flare to Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    72
    6
    14
    Units: scores on a scale
        arithmetic mean (standard deviation)
    -2.52 ± 2.46
    -0.72 ± 0.70
    -1.83 ± 2.38
    No statistical analyses for this end point

    Secondary: Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The BASMI is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From time of flare to Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    67
    6
    15
    Units: scores on a scale
        arithmetic mean (standard deviation)
    -0.43 ± 0.58
    -0.27 ± 0.35
    -0.26 ± 0.30
    No statistical analyses for this end point

    Secondary: Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) score at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The SPARCC scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total Sacroiliac (SI) joint SPARCC score can range from 0 to 72 with higher scores indicating higher joint inflammation. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From time of flare to Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    48
    2
    12
    Units: scores on a scale
        arithmetic mean (standard deviation)
    -9.3 ± 13.2
    0.0 ± 0.0
    0.2 ± 3.1
    No statistical analyses for this end point

    Secondary: Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for activity (ASspIMRI-a) in the Berlin modification score at Escape Week 12 for participants who experienced a flare in Part B

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    End point title
    Change from Baseline in spine Ankylosing Spondylitis spine Magnetic Resonance Imaging Score for activity (ASspIMRI-a) in the Berlin modification score at Escape Week 12 for participants who experienced a flare in Part B
    End point description
    The Berlin modification of the ASspiMRI-a is a scoring system with a concentration on Short-Tau-Inversion Recovery (STIR) sequences without other fat saturation techniques. It quantifies changes in 23 Vertebral Units (VU) of the spine. Active inflammation was scored by grading the degree of bone marrow edema from 0 to 3 in 1 dimension on 1 or more consecutive slices that represent the highest level of inflammation in a particular VU. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.
    End point type
    Secondary
    End point timeframe
    From time of flare to Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS) CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
    Number of subjects analysed
    48
    2
    12
    Units: scores on a scale
        arithmetic mean (standard deviation)
    -2.3 ± 4.6
    0.0 ± 0.0
    -0.3 ± 1.0
    No statistical analyses for this end point

    Secondary: Certolizumab pegol (CZP) Plasma Concentration during the study

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    End point title
    Certolizumab pegol (CZP) Plasma Concentration during the study
    End point description
    CZP plasma concentration was measured in micrograms per milliliter (μg/mL). Blood sample measurements that were deemed to be below the level of quantification, were set to half the lower level of quantification (LLOQ) for analysis purposes. Summary statistics were only displayed if at least two-thirds of the values were above the LLOQ and if n was greater or equal to (>=) 4. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the PK of these patients. The CZP plasma concentration of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP. Note: Number of participants analyzed each Week is presented in parentheses following the model: (PBO, CZP 200 mg Q2W, CZP 200 mg Q4W). 999 is used as a placeholder for values below the level of detection.
    End point type
    Secondary
    End point timeframe
    From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
    End point values
    Placebo Double-Blind (PKSB) Certolizumab pegol 200 mg Q2W Double-Blind (PKSB) Certolizumab pegol 200 mg Q4W Double-Blind (PKSB)
    Number of subjects analysed
    101
    102
    105
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Part A Baseline (99, 101, 105)
    999 ± 999
    999 ± 999
    999 ± 999
        Week 4 (101, 100, 104)
    48.71 ± 85.76
    53.39 ± 30.93
    48.92 ± 43.17
        Week 12 (100, 101, 105)
    30.91 ± 89.23
    31.74 ± 50.79
    30.69 ± 56.82
        Week 24 (100, 101, 104)
    26.31 ± 135.58
    30.23 ± 46.57
    28.96 ± 58.38
        Week 48/Part B Baseline (98, 100, 104)
    36.28 ± 74.18
    36.59 ± 84.36
    31.11 ± 138.29
        Week 60 (98, 100, 105)
    999 ± 999
    27.76 ± 49.47
    6.95 ± 178.27
        Week 72 (76, 95, 99)
    999 ± 999
    26.36 ± 105.58
    7.61 ± 176.39
        Week 84 (38, 91, 90)
    999 ± 999
    26.57 ± 44.90
    8.00 ± 113.48
        Week 96 (27, 86, 85)
    999 ± 999
    24.76 ± 97.60
    7.16 ± 131.76
        Withdrawal Visit (4, 3, 5)
    0.81 ± 1802.40
    999 ± 999
    0.30 ± 2621.06
        Escape Week 0/Flare Baseline (72, 6, 14)
    999 ± 999
    30.77 ± 19.78
    12.70 ± 98.45
        Escape Week 2 (71, 6, 15)
    18.27 ± 488.45
    33.50 ± 21.17
    15.43 ± 124.10
        Escape Week 4 (71, 6, 15)
    37.32 ± 151.18
    32.94 ± 30.48
    18.43 ± 79.93
        Escape Week 12 (69, 6, 15)
    23.89 ± 232.36
    23.76 ± 65.42
    19.14 ± 136.22
        Escape Week 24 (54, 3, 8)
    27.47 ± 45.31
    999 ± 999
    19.23 ± 66.68
        Escape Week 36 (14, 3, 3)
    24.88 ± 77.53
    999 ± 999
    999 ± 999
        Last Visit (Week 96) (66, 6, 14)
    24.64 ± 112.75
    26.19 ± 54.74
    18.59 ± 95.75
        Withdrawal Escape Visit (4, 1, 0)
    4.71 ± 133329.3
    999 ± 999
    0 ± 0
        Safety Follow-up (92, 92, 98)
    999 ± 999
    0.52 ± 1158.85
    0.14 ± 772.54
    No statistical analyses for this end point

    Secondary: Percentage of participants with positive anti-certolizumab pegol-antibody levels in plasma during the study

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    End point title
    Percentage of participants with positive anti-certolizumab pegol-antibody levels in plasma during the study
    End point description
    Treatment emergent ADAb status positive was defined as either baseline ADAb negative subjects having at least one ADAb confirmed positive sample post baseline or baseline ADAb positive subjects with at least one post baseline sample with >= minimum significant ratio (MSR) increase from baseline on CZP treatment. Once determined positive, the highest titer during Part A and Part B (including Escape and Safety Follow up) was used to categorize the subject. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the immunogenicity of these patients. The ADAb titer of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP.
    End point type
    Secondary
    End point timeframe
    From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
    End point values
    Placebo Double-Blind (PKSB) Certolizumab pegol 200 mg Q2W Double-Blind (PKSB) Certolizumab pegol 200 mg Q4W Double-Blind (PKSB)
    Number of subjects analysed
    101
    102
    105
    Units: percentage of participants
        number (not applicable)
    100
    96.1
    100
    No statistical analyses for this end point

    Secondary: Percentage of participants with at least one Adverse Event (AE) during Part A of the study

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    End point title
    Percentage of participants with at least one Adverse Event (AE) during Part A of the study
    End point description
    An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
    End point type
    Secondary
    End point timeframe
    From Screening Period (Week -5 to Week -1) until Week 48
    End point values
    Certolizumab pegol Open-Label (SS) Wk 0-48
    Number of subjects analysed
    736
    Units: percentage of participants
    number (not applicable)
        Screening Period (Week -5 to Week -1)
    7.3
        Open-Label Period (Week 0 to Week 48)
    67.9
    No statistical analyses for this end point

    Secondary: Percentage of participants with at least one Adverse Event (AE) during Part B of the study

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    End point title
    Percentage of participants with at least one Adverse Event (AE) during Part B of the study
    End point description
    An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. For subjects with flare in Part B and do escape to CZP full-dose therapy, only TEAEs with an onset date prior to the start date of escape CZP full-dose therapy were included.
    End point type
    Secondary
    End point timeframe
    From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
    End point values
    Placebo Double-Blind (SSB) Wk 48–96 Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96 Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96
    Number of subjects analysed
    103
    104
    105
    Units: percentage of participants
        number (not applicable)
    54.4
    57.7
    61.0
    No statistical analyses for this end point

    Secondary: Percentage of participants with at least one Adverse Event (AE) and who experienced a flare during Part B of the study

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    End point title
    Percentage of participants with at least one Adverse Event (AE) and who experienced a flare during Part B of the study
    End point description
    An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. For subjects with flare in Part B and do escape to CZP full-dose therapy, only TEAEs with an onset date after or on the start date of escape CZP full-dose therapy were included.
    End point type
    Secondary
    End point timeframe
    From time of flare to Escape Week 12
    End point values
    Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12 CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12 CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
    Number of subjects analysed
    72
    6
    15
    Units: percentage of participants
        number (not applicable)
    51.4
    83.3
    46.7
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from Week 0 (Baseline) until the Safety Follow-Up Period (10 weeks after the last dose of study medication).
    Adverse event reporting additional description
    TEAEs counts are for each study period: Open-Label (Wk0-48), Double-Blind (Wk48-96) and Escape (Wk0-12). During Escape (last 3 columns) all participants received CZP 200 mg Q2W at time of TEAEs, although they were coming from 3 arms of the double-blind phase. Participants randomized or who entered escape but received no treatment are not included.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Certolizumab pegol Open-Label (SS) Wk 0-48
    Reporting group description
    Participants in this arm received certolizumab pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 to Week 48 (Part A). Participants in sustained remission at Week 48 were eligible for randomization into Part B. Participants formed the Safety Set (SS).

    Reporting group title
    Placebo Double-Blind (SSB) Wk 48–96
    Reporting group description
    Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards. Participants formed the Safety Set Part B (SSB).

    Reporting group title
    Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96
    Reporting group description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards. Participants formed the SSB.

    Reporting group title
    Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96
    Reporting group description
    Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards. At visits where CZP was not received, subjects received one injection of Placebo to maintain the study blind. Participants formed the SSB.

    Reporting group title
    Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
    Reporting group description
    Participants randomized to Placebo who met flare criteria received CZP 400 mg subcutaneous (sc) every 2 weeks (Q2W) for the first 3 visits after flare has been confirmed. After that, CZP 200 mg was given every 2 weeks in open-label fashion. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the Escape Therapy Set (ETS).

    Reporting group title
    CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
    Reporting group description
    Participants randomized to CZP 200 mg Q2W who meet flare criteria received CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, participants received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the ETS.

    Reporting group title
    CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
    Reporting group description
    Participants randomized to CZP 200 mg Q4W who meet flare criteria received CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, participants received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind. The duration was from starting escape treatment after flare until Week 96 with a minimum of 12 weeks. Participants formed the ETS.

    Serious adverse events
    Certolizumab pegol Open-Label (SS) Wk 0-48 Placebo Double-Blind (SSB) Wk 48–96 Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96 Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96 Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12 CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12 CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
    Total subjects affected by serious adverse events
         subjects affected / exposed
    44 / 736 (5.98%)
    0 / 103 (0.00%)
    5 / 104 (4.81%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy on contraceptive
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Schizophrenia
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometrial hyperplasia
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Meniscus injury
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epicondylitis
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    False positive tuberculosis test
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal septum deviation
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Migraine
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Optic neuritis
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal vein occlusion
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis acute
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    1 / 104 (0.96%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    2 / 736 (0.27%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glossitis
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    1 / 104 (0.96%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    1 / 104 (0.96%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureterolithiasis
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis atopic
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyshidrotic eczema
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pustular psoriasis
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Axial spondyloarthritis
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    2 / 736 (0.27%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis aseptic
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulpitis dental
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis E
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tuberculous pleurisy
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    1 / 104 (0.96%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Latent tuberculosis
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    1 / 104 (0.96%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Certolizumab pegol Open-Label (SS) Wk 0-48 Placebo Double-Blind (SSB) Wk 48–96 Certolizumab pegol 200 mg Q2W Double-Blind (SSB) Wk 48–96 Certolizumab pegol 200 mg Q4W Double-Blind (SSB) Wk 48–96 Placebo DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12 CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12 CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (ETS) Escape Wk 0–>=12
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    188 / 736 (25.54%)
    25 / 103 (24.27%)
    31 / 104 (29.81%)
    26 / 105 (24.76%)
    20 / 72 (27.78%)
    5 / 6 (83.33%)
    7 / 15 (46.67%)
    Investigations
    Antinuclear antibody increased
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    12 / 736 (1.63%)
    0 / 103 (0.00%)
    3 / 104 (2.88%)
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    14
    0
    3
    2
    0
    0
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    4 / 736 (0.54%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    2
    0
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Nervous system disorders
    Cervicogenic vertigo
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Sciatica
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Eye disorders
    Iritis
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    8 / 736 (1.09%)
    1 / 103 (0.97%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences all number
    9
    1
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Irritable bowel syndrome
         subjects affected / exposed
    2 / 736 (0.27%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Axial spondyloarthritis
         subjects affected / exposed
    8 / 736 (1.09%)
    8 / 103 (7.77%)
    6 / 104 (5.77%)
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    8
    8
    6
    1
    0
    0
    0
    Joint stiffness
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    117 / 736 (15.90%)
    8 / 103 (7.77%)
    12 / 104 (11.54%)
    13 / 105 (12.38%)
    8 / 72 (11.11%)
    2 / 6 (33.33%)
    1 / 15 (6.67%)
         occurrences all number
    156
    8
    17
    18
    9
    2
    1
    Upper respiratory tract infection
         subjects affected / exposed
    63 / 736 (8.56%)
    10 / 103 (9.71%)
    12 / 104 (11.54%)
    11 / 105 (10.48%)
    5 / 72 (6.94%)
    1 / 6 (16.67%)
    1 / 15 (6.67%)
         occurrences all number
    88
    12
    14
    12
    7
    1
    1
    Pharyngitis
         subjects affected / exposed
    22 / 736 (2.99%)
    3 / 103 (2.91%)
    2 / 104 (1.92%)
    6 / 105 (5.71%)
    2 / 72 (2.78%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    24
    3
    2
    6
    2
    0
    1
    Oral herpes
         subjects affected / exposed
    13 / 736 (1.77%)
    2 / 103 (1.94%)
    1 / 104 (0.96%)
    2 / 105 (1.90%)
    1 / 72 (1.39%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences all number
    21
    3
    3
    2
    1
    3
    0
    Hordeolum
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Influenza
         subjects affected / exposed
    9 / 736 (1.22%)
    1 / 103 (0.97%)
    3 / 104 (2.88%)
    1 / 105 (0.95%)
    2 / 72 (2.78%)
    1 / 6 (16.67%)
    0 / 15 (0.00%)
         occurrences all number
    9
    1
    3
    1
    3
    1
    0
    Bronchitis
         subjects affected / exposed
    24 / 736 (3.26%)
    3 / 103 (2.91%)
    0 / 104 (0.00%)
    3 / 105 (2.86%)
    1 / 72 (1.39%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    25
    3
    0
    3
    1
    0
    1
    Conjunctivitis
         subjects affected / exposed
    6 / 736 (0.82%)
    1 / 103 (0.97%)
    0 / 104 (0.00%)
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    6
    1
    0
    1
    0
    0
    1
    Furuncle
         subjects affected / exposed
    1 / 736 (0.14%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    0 / 105 (0.00%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    Laryngitis
         subjects affected / exposed
    0 / 736 (0.00%)
    0 / 103 (0.00%)
    0 / 104 (0.00%)
    1 / 105 (0.95%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    1
    Latent tuberculosis
         subjects affected / exposed
    5 / 736 (0.68%)
    0 / 103 (0.00%)
    3 / 104 (2.88%)
    2 / 105 (1.90%)
    1 / 72 (1.39%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    5
    0
    3
    2
    1
    0
    1
    Sinusitis
         subjects affected / exposed
    12 / 736 (1.63%)
    1 / 103 (0.97%)
    0 / 104 (0.00%)
    2 / 105 (1.90%)
    0 / 72 (0.00%)
    0 / 6 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    12
    1
    0
    2
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Nov 2015
    Global Protocol Amendment 1 (dated 24 Nov 2015) was a substantial protocol amendment implemented to include additional efficacy variables for study participants who entered Part A and Part B of the study, as well as a completely new list of other efficacy variables for those study participants who experienced a flare in Part B. For the purposes of analysis, 4 new analysis sets were defined, 2 of which were to be used in the pharmacokinetic (PK) analysis, 1 which was to be used in the efficacy analysis of study participants who experienced a flare in Part B, and 1 which was to be used to evaluate safety in study participants who ever received treatment with full-dose CZP during Part B of the study. Several clarifications were made including the time point for the assessment of the secondary efficacy variables for study participants who experienced a flare in Part B, human leukocyte antigen B27 (HLA-B27) as a Screening laboratory assessment, and the assessments to be performed 3 to 5 days prior to Week 48. Inconsistencies in the naming of Week 96 Visit and assessments were corrected, study personnel information was updated, and minor editorial changes were made.

    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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