Study to Evaluate Maintenance of Sustained Remission of a... | NCT02505542 | Trialant
NCT02505542
Sponsor
UCB BIOSCIENCES GmbH
Status
Completed
Last Update Posted
Dec 17, 2020Actual
Enrollment
736Actual
Phase
Phase 3
Conditions
Axial Spondyloarthrithis
Ankylosing Spondylitis
Interventions
Certolizumab Pegol
Placebo
Countries
United States
Belgium
Bulgaria
Czechia
France
Germany
Hungary
Netherlands
Poland
Romania
Spain
Taiwan
Turkey (Türkiye)
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02505542
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
AS0005
Secondary IDs
ID
Type
Description
Link
2015-000339-34
EudraCT Number
Brief Title
Study to Evaluate Maintenance of Sustained Remission of axSpA With CZP Compared to Placebo
Official Title
A 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 200 mg Q2W or 200 mg Q4W as Compared to Placebo
Acronym
C-OPTIMISE
Organization
UCB PharmaINDUSTRY
Status Module
Record Verification Date
Nov 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
YesNCT03559686No longer available
Start Date
Jul 2015Actual
Primary Completion Date
Feb 2019Actual
Completion Date
Apr 2019Actual
First Submitted Date
Jul 16, 2015
First Submission Date that Met QC Criteria
Jul 20, 2015
First Posted Date
Jul 22, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Feb 26, 2020
Results First Submitted that Met QC Criteria
Apr 10, 2020
Results First Posted Date
Apr 21, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Nov 26, 2020
Last Update Posted Date
Dec 17, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
UCB BIOSCIENCES GmbHINDUSTRY
Collaborators
Name
Class
Parexel
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Patients receive study drug for one year (Part A). If, after the initial run-in phase, a sustained remission is reached they will be randomly split into one of three dose groups for another year (Part B). The maintenance of the sustained remission will be analyzed.
Detailed Description
Not provided
Conditions Module
Conditions
Axial Spondyloarthrithis
Ankylosing Spondylitis
Keywords
Axial Spondyloarthritis
axSpA
Ankylosing Spondylitis
Anti TNF-alpha
Certolizumab Pegol
Remission
Spondylarthropathies
Arthritis
Spinal Diseases
Immunosuppressive Agents
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
736Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Open-label Certolizumab Pegol
Other
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). Subjects in sustained remission at Week 48 are eligible for randomization into Part B.
Biological: Certolizumab Pegol
Double-blind Certolizumab Pegol 200 mg Q2W
Experimental
Certolizumab Pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Biological: Certolizumab Pegol
Double-blind Certolizumab Pegol 200 mg Q4W
Experimental
Certolizumab Pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards.
At visits where CZP is not received, subjects receive one injection of Placebo to maintain the study blind.
Biological: Certolizumab Pegol
Other: Placebo
Placebo
Placebo Comparator
One placebo injection is administered every 2 weeks from Week 48 onwards.
Other: Placebo
Placebo to CZP 200 mg Q2W escape
Other
Subjects randomized to Placebo who meet flare criteria receive CZP 400 mg subcutaneous (sc) every 2 weeks (Q2W) for the first 3 visits after flare has been confirmed. After that, CZP 200 mg is given every 2 weeks in open-label fashion.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Certolizumab Pegol
Biological
Active substance: Certolizumab Pegol
Pharmaceutical form: Prefilled syringe
Concentration: 200 mg / ml
Route of Administration: Subcutaneous injection
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of Participants in Part B Who Did Not Experienced a Flare
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.
From Week 48 to Week 96
Secondary Outcomes
Measure
Description
Time Frame
Percentage of Participants Achieving Sustained Remission at Week 48 in Part A
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Documented diagnosis of adult-onset axial SpondyloArthritis (axSpA) with at least 3 months' symptom duration and meet the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA and symptom duration of less than 5 years prior to the participation of this study
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4
Spinal pain > 4 on a 0 to 10 Numerical Rating Scale (NRS) (from BASDAI Item 2)
for modified New York (mNY) -negative subjects only: C-reactive Protein (CRP) > upper limit of normal (ULN) and/or current evidence for sacroiliitis on the Screening Magnetic Resonance Imaging (MRI)
Inadequate response to, or contraindication to, or intolerant to at least 2 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Exclusion Criteria:
Presence of total Spinal Ankylosis ('bamboo spine')
Diagnosis of any other Inflammatory Arthritis
Prior treatment with any experimental biological agents for treatment of Axial SpondyloArthritis (SpA)
Exposure to more than 1 TNF-antagonist or primary failure to TNF antagonist therapy
History of or current chronic or recurrent infections
High risk of infection
Recent live vaccination
Concurrent malignancy or a history of malignancy
Class III or IV congestive heart failure - New York Heart Association (NYHA)
Demyelinating disease of the central nervous system
Female subjects who are breastfeeding, pregnant or plan to become pregnant during the study or within 3 months following the last dose of the investigational product
Subjects with any other condition which, in the investigator's judgment, would make the subject unsuitable for inclusion in the study
Landewe RB, van der Heijde D, Dougados M, Baraliakos X, Van den Bosch FE, Gaffney K, Bauer L, Hoepken B, Davies OR, de Peyrecave N, Thomas K, Gensler LS. Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction. Ann Rheum Dis. 2020 Jul;79(7):920-928. doi: 10.1136/annrheumdis-2019-216839. Epub 2020 May 7.
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.
Recruitment Details
The study started to enroll patients in July 2015 and concluded in April 2019.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Certolizumab Pegol Open-Label
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.
FG001
Periods
Title
Milestones
Reasons Not Completed
Part A: Open-Label Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
SAP
No
Yes
No
Statistical Analysis Plan
May 7, 2019
Feb 26, 2020
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Biological: Certolizumab Pegol
Other: Placebo
CZP 200 mg Q4W to CZP 200 mg Q2W escape
Other
Subjects randomized to CZP 200 mg Q4W who meet flare criteria receive 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, subjects receive one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.
Biological: Certolizumab Pegol
Other: Placebo
CZP 200 mg Q2W to CZP 200 mg Q2W escape
Other
Subjects randomized to CZP 200 mg Q2W who meet flare criteria receive 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, subjects receive one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.
Biological: Certolizumab Pegol
Other: Placebo
CZP 200 mg Q2W to CZP 200 mg Q2W escape
CZP 200 mg Q4W to CZP 200 mg Q2W escape
Double-blind Certolizumab Pegol 200 mg Q2W
Double-blind Certolizumab Pegol 200 mg Q4W
Open-label Certolizumab Pegol
Placebo to CZP 200 mg Q2W escape
Cimzia
CDP870
Placebo
Other
Active substance: Placebo
Pharmaceutical form: Prefilled syringe
Concentration: 0.9 % Saline
Route of Administration: Subcutaneous injection
CZP 200 mg Q2W to CZP 200 mg Q2W escape
CZP 200 mg Q4W to CZP 200 mg Q2W escape
Double-blind Certolizumab Pegol 200 mg Q4W
Placebo
Placebo to CZP 200 mg Q2W escape
Week 48
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A
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-very High Disease activity (ASDAS-vHD): ASDAS > 3.5
Missing data were handled using last observation carried forward (LOCF) methods.
Week 48
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 48 in Part A
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.
Week 48
Time to Flare in Part B
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.
From Week 48 to Week 96
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B
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-very High Disease activity (ASDAS-vHD): ASDAS > 3.5
Week 96
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B
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.
Week 96
Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Week 96 in Part B
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.
Week 96
Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Week 96 in Part B
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.
Week 96
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Week 96 in Part B
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.
Week 96
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Week 96 in Part B
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.
Week 96
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B
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.
From Week 48 to Week 96
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B
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.
From Week 48 to Week 96
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B
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.
From Week 48 to Week 96
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B
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.
From Week 48 to Week 96
Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Criteria Response at Week 96 in Part B
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.
Week 96
Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 96 in Part B
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.
From Week 48 to Week 96
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
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.
From Week 48 to Week 96
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
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-very High Disease activity (ASDAS-vHD): ASDAS > 3.5
Escape Week 12
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
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
Escape Week 12
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
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].
Escape Week 12
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
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.
Escape Week 12
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
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).
Escape Week 12
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
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.
Escape Week 12
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for Participants Who Experienced a Flare in Part B
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.
From time of flare to Escape Week 12
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
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.
From time of flare to Escape Week 12
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
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.
From time of flare to Escape Week 12
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
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.
From time of flare to Escape Week 12
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
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.
From time of flare to Escape Week 12
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
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.
From time of flare to Escape Week 12
Certolizumab Pegol (CZP) Plasma Concentration During the Study
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.
From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
Percentage of Participants With Positive Anti-certolizumab Pegol-antibody Levels in Plasma During the Study
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.
From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
Percentage of Participants With at Least One Adverse Event (AE) During Part A of the Study
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.
From Screening Period (Week -5 to Week -1) until Week 48
Percentage of Participants With at Least One Adverse Event (AE) During Part B of the Study
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.
From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
Percentage of Participants With at Least One Adverse Event (AE) and Who Experienced a Flare During Part B of the Study
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.
From time of flare to Escape Week 12
Mesa
Arizona
85202
United States
As0005 2314
Phoenix
Arizona
85037
United States
As0005 2317
Sun City
Arizona
85351
United States
As0005 2307
Palm Desert
California
92260
United States
As0005 2310
San Francisco
California
94143
United States
As0005 2305
Upland
California
91786
United States
As0005 2308
Denver
Colorado
80230
United States
As0005 2302
Brandon
Florida
33511
United States
As0005 2321
Hagerstown
Maryland
21742
United States
As0005 2312
Minot
North Dakota
58701
United States
As0005 2323
Oklahoma City
Oklahoma
73101
United States
As0005 2311
Duncansville
Pennsylvania
16635
United States
As0005 2315
Jackson
Tennessee
38305
United States
As0005 2303
Austin
Texas
78731
United States
As0005 2318
Dallas
Texas
75231
United States
As0005 1006
Genk
Belgium
As0005 1001
Ghent
Belgium
As0005 1004
Merksem
Belgium
As0005 1003
Mons
Belgium
As0005 1109
Pleven
Bulgaria
As0005 1103
Plovdiv
Bulgaria
As0005 1106
Plovdiv
Bulgaria
As0005 1111
Rousse
Bulgaria
As0005 1110
Sevlievo
Bulgaria
As0005 1101
Sofia
Bulgaria
As0005 1108
Sofia
Bulgaria
As0005 1308
Brno
Czechia
As0005 1309
Bruntál
Czechia
As0005 1301
Kladno
Czechia
As0005 1307
Ostrava
Czechia
As0005 1303
Pardubice
Czechia
As0005 1302
Prague
Czechia
As0005 1305
Prague
Czechia
As0005 1306
Prague
Czechia
As0005 1310
Prague
Czechia
As0005 1311
Prague
Czechia
As0005 1314
Prague
Czechia
As0005 1313
Uherské Hradiště
Czechia
As0005 1304
Zlín
Czechia
As0005 1504
Montpellier
France
As0005 1505
Orléans
France
As0005 1501
Paris
France
As0005 1503
Tours
France
As0005 1406
Berlin
Germany
As0005 1408
Berlin
Germany
As0005 1410
Berlin
Germany
As0005 1412
Berlin
Germany
As0005 1413
Bochum
Germany
As0005 1407
Cologne
Germany
As0005 1405
Erlangen
Germany
As0005 1404
Frankfurt am Main
Germany
As0005 1402
Hamburg
Germany
As0006 1409
Herne
Germany
As0005 1403
Leipzig
Germany
As0005 1705
Budapest
Hungary
As0005 1710
Budapest
Hungary
As0005 1704
Debrecen
Hungary
As0005 1706
Miskolc
Hungary
As0005 1711
Nyíregyháza
Hungary
As0005 1707
Szeged
Hungary
As0005 1702
Szentes
Hungary
As0005 1703
Szombathely
Hungary
As0005 1701
Veszprém
Hungary
As0005 2502
Amsterdam
Netherlands
As0005 2503
Rotterdam
Netherlands
As0005 2501
Sneek
Netherlands
As0005 1806
Bialystok
Poland
As0005 1805
Bydgoszcz
Poland
As0005 1801
Elblag
Poland
As0005 1802
Elblag
Poland
As0005 1812
Krakow
Poland
As0005 1808
Lodz
Poland
As0005 1814
Lodz
Poland
As0005 1803
Lublin
Poland
As0005 1816
Ostrowiec Świętokrzyski
Poland
As0005 1809
Poznan
Poland
As0005 1813
Poznan
Poland
As0005 1807
Torun
Poland
As0005 1804
Warsaw
Poland
As0005 1811
Warsaw
Poland
As0005 1815
Warsaw
Poland
As0005 1912
Brasov
Romania
As0005 1904
Brăila
Romania
As0005 1902
Bucharest
Romania
As0005 1903
Bucharest
Romania
As0005 1913
Bucharest
Romania
As0005 1907
Cluj-Napoca
Romania
As0005 1910
Iași
Romania
As0005 1911
Târgu Mureş
Romania
As0005 2403
Córdoba
Spain
As0005 2404
Getafe
Spain
As0005 2401
Madrid
Spain
As0005 2402
Seville
Spain
As0005 2205
Kaohsiung City
Taiwan
As0005 2201
Taichung
Taiwan
As0005 2202
Taichung
Taiwan
As0005 2203
Taipei
Taiwan
As0005 2204
Taipei
Taiwan
As0005 2206
Taipei
Taiwan
As0005 2101
Ankara
Turkey (Türkiye)
As0005 2103
Edirne
Turkey (Türkiye)
As0005 2102
Gaziantep
Turkey (Türkiye)
As0005 2105
Istanbul
Turkey (Türkiye)
As0005 2106
Istanbul
Turkey (Türkiye)
As0005 2104
Izmir
Turkey (Türkiye)
As0005 1603
Leeds
United Kingdom
As0005 1601
Norwich
United Kingdom
Derived
Proft F, Vahldiek JL, Nicolaes J, Tham R, Hoepken B, Ufuktepe B, Poddubnyy D, Bressem KK. Machine learning vs human experts: sacroiliitis analysis from the RAPID-axSpA and C-OPTIMISE phase 3 axSpA trials. Rheumatol Adv Pract. 2025 Apr 18;9(2):rkae118. doi: 10.1093/rap/rkae118. eCollection 2025.
Baraliakos X, Machado PM, Bauer L, Hoepken B, Kim M, Kumke T, Tham R, Rudwaleit M. Comparison of established and preliminarily proposed ASAS MRI working group cut-offs for inflammatory MRI lesions in the sacroiliac joints in radiographic and non-radiographic axial spondyloarthritis. RMD Open. 2024 Sep 3;10(3):e003886. doi: 10.1136/rmdopen-2023-003886.
Landewe R, van der Heijde D, Dougados M, Baraliakos X, Van den Bosch F, Gaffney K, Bauer L, Hoepken B, de Peyrecave N, Thomas K, Gensler LS. Induction of Sustained Clinical Remission in Early Axial Spondyloarthritis Following Certolizumab Pegol Treatment: 48-Week Outcomes from C-OPTIMISE. Rheumatol Ther. 2020 Sep;7(3):581-599. doi: 10.1007/s40744-020-00214-7. Epub 2020 Jun 11.
Placebo Double-Blind
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
FG002
Certolizumab Pegol 200 mg Q2W Double-Blind
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
FG003
Certolizumab Pegol 200 mg Q4W Double-Blind
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.
FG000736 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
COMPLETED
FG000659 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
NOT COMPLETED
FG00077 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Type
Comment
Reasons
Adverse Event
FG00031 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Lack of Efficacy
FG0005 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Protocol Violation
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Lost to Follow-up
FG0005 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Withdrawal by Subject
FG00027 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
New medical history available
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Participant did not attend week 48 visit
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Pregnancy
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Sponsor directive
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Medical monitor decision
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Screening failure (detected too late)
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Non-compliance
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Completed Part A, Did Not Enter Part B
Type
Comment
Milestone Data
STARTED
FG000659 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
COMPLETED
FG000313 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
NOT COMPLETED
FG000346 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
Type
Comment
Reasons
Lack of Efficacy
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG003
Part B: Double-Blind Period
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG001104 subjects
FG002104 subjects
FG003105 subjects
Started Escape Period
FG0000 subjects
FG00173 subjects
FG0027 subjects
FG00315 subjects
COMPLETED
FG0000 subjects
FG00192 subjects
FG00295 subjects
FG00398 subjects
NOT COMPLETED
FG0000 subjects
FG00112 subjects
FG0029 subjects
FG0037 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG003
Baseline Characteristics refer to the The Open-Label Set (OLS) which consisted of all study participants who received at least 1 dose of investigational medicinal product (IMP) in the Open-Label Period of the study (Part A).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Certolizumab Pegol Open-Label
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.
Denominators
Units
Counts
Participants
BG000736
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0007
Between 18 and 65 years
BG000729
>=65 years
BG000
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00032.9± 7.0
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000222
Male
BG000514
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American indian/alaskan native
BG0002
Asian
BG00038
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Percentage of Participants in Part B Who Did Not Experienced a Flare
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Number
95% Confidence Interval
percentage of participants
From Week 48 to Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG00020.2(13.0 to 29.2)
OG00183.7(75.1 to 90.2)
OG00279.0(70.0 to 86.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
Regression, Logistic
<0.001
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.
Odds Ratio (OR)
18.822
2-Sided
95
9.605
38.864
Secondary
Percentage of Participants Achieving Sustained Remission at Week 48 in Part A
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.
The Open-Label Set (OLS) consisted of all study participants who received at least 1 dose of investigational medicinal product (IMP) in the Open-Label Period of the study (Part A).
Posted
Number
95% Confidence Interval
percentage of participants
Week 48
ID
Title
Description
OG000
Certolizumab Pegol Open-Label (OLS)
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).
Units
Counts
Participants
OG000
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A
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-very High Disease activity (ASDAS-vHD): ASDAS > 3.5
Missing data were handled using last observation carried forward (LOCF) methods.
The Open-Label Set (OLS) consisted of all study participants who received at least 1 dose of IMP in the Open-Label Period of the study (Part A).
Posted
Number
percentage of participants
Week 48
ID
Title
Description
OG000
Certolizumab Pegol Open-Label (OLS)
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).
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 48 in Part A
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.
The Open-Label Set (OLS) consisted of all study participants who received at least 1 dose of IMP in the Open-Label Period of the study (Part A).
Posted
Number
percentage of participants
Week 48
ID
Title
Description
OG000
Certolizumab Pegol Open-Label (OLS)
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).
Secondary
Time to Flare in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Median
Inter-Quartile Range
days
From Week 48 to Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B
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-very High Disease activity (ASDAS-vHD): ASDAS > 3.5
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Number
percentage of participants
Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
Secondary
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Number
percentage of participants
Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Number
percentage of participants
Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Number
percentage of participants
Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Number
percentage of participants
Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Secondary
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Number
percentage of participants
Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Secondary
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Least Squares Mean
Standard Error
scores on a scale
From Week 48 to Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Least Squares Mean
Standard Error
scores on a scale
From Week 48 to Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Least Squares Mean
Standard Error
scores on a scale
From Week 48 to Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Least Squares Mean
Standard Error
scores on a scale
From Week 48 to Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
Secondary
Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Criteria Response at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
Posted
Number
percentage of participants
Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Secondary
Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 96 in Part B
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
The number of participants analyzed reflects Week 96.
Posted
Mean
Standard Deviation
scores on a scale
From Week 48 to Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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
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.
The Randomized Set (RS) consisted of all study participants randomized into Part B of the study.
The number of participants analyzed reflects Week 96.
Posted
Mean
Standard Deviation
scores on a scale
From Week 48 to Week 96
ID
Title
Description
OG000
Placebo Double-Blind (RS)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Randomized Set (RS).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (RS)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
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
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-very High Disease activity (ASDAS-vHD): ASDAS > 3.5
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
Posted
Number
percentage of participants
Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
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
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
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
Posted
Number
percentage of participants
Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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
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].
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
Posted
Number
percentage of participants
Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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
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.
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
Posted
Number
percentage of participants
Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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.
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
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).
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
Posted
Number
percentage of participants
Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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.
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
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.
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
Posted
Number
percentage of participants
Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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.
Secondary
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for Participants Who Experienced a Flare in Part B
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.
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
The number of participants analyzed reflects Escape Week 12.
Posted
Mean
Standard Deviation
scores on a scale
From time of flare to Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
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
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.
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
The number of participants analyzed reflects Escape Week 12.
Posted
Mean
Standard Deviation
scores on a scale
From time of flare to Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
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.
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
The number of participants analyzed reflects Escape Week 12.
Posted
Mean
Standard Deviation
scores on a scale
From time of flare to Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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.
Secondary
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for Participants Who Experienced a Flare in Part B
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.
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
The number of participants analyzed reflects Escape Week 12.
Posted
Mean
Standard Deviation
scores on a scale
From time of flare to Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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
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.
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
The number of participants analyzed reflects Escape Week 12.
Posted
Mean
Standard Deviation
scores on a scale
From time of flare to Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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.
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
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.
The Flared Set (FS) consisted of all study participants from the RS who experienced a flare in Part B.
The number of participants analyzed reflects Escape Week 12.
Posted
Mean
Standard Deviation
scores on a scale
From time of flare to Escape Week 12
ID
Title
Description
OG000
Placebo DB/CZP 200 mg Q2W Escape (FS)
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).
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
Secondary
Certolizumab Pegol (CZP) Plasma Concentration During the Study
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.
The Pharmacokinetic Set B (PKSB) consisted of all study participants from the Safety Set Part B (SSB) who provided at least 1 PK sample during Part B.
Posted
Geometric Mean
Geometric Coefficient of Variation
μg/mL
From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
ID
Title
Description
OG000
Placebo Double-Blind (PKSB)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Pharmacokinetic Set B (PKSB).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (PKSB)
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the PKSB.
Secondary
Percentage of Participants With Positive Anti-certolizumab Pegol-antibody Levels in Plasma During the Study
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.
The Pharmacokinetic Set B (PKSB) consisted of all study participants from the Safety Set Part B (SSB) who provided at least 1 PK sample during Part B.
Posted
Number
percentage of participants
From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
ID
Title
Description
OG000
Placebo Double-Blind (PKSB)
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants formed the Pharmacokinetic Set B (PKSB).
OG001
Certolizumab Pegol 200 mg Q2W Double-Blind (PKSB)
Secondary
Percentage of Participants With at Least One Adverse Event (AE) During Part A of the Study
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.
The Safety Set (SS) consisted of all study participants in the Enrolled Set (ES) who received at least 1 dose of investigational medicinal product (IMP).
Posted
Number
percentage of participants
From Screening Period (Week -5 to Week -1) until Week 48
ID
Title
Description
OG000
Certolizumab Pegol Open-Label (SS) Wk 0-48
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).
Units
Counts
Participants
Secondary
Percentage of Participants With at Least One Adverse Event (AE) During Part B of the Study
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.
The Safety Set Part B (SSB) consisted of all study participants in the Randomized Set (RS) who received at least 1 dose of IMP in the Double-Blind Period of the study (Part B).
Posted
Number
percentage of participants
From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
ID
Title
Description
OG000
Placebo Double-Blind (SSB) Wk 48-96
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the SSB.
Secondary
Percentage of Participants With at Least One Adverse Event (AE) and Who Experienced a Flare During Part B of the Study
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.
The Escape Therapy Set (ETS) consisted of all study participants from the Flared Set (FS) who received at least 1 dose of escape treatment.
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.
Adverse events were collected from Week 0 (Baseline) until the Safety Follow-Up Period (10 weeks after the last dose of study medication).
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.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Certolizumab Pegol Open-Label (SS) Wk 0-48
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).
0
736
44
736
188
736
EG001
Placebo Double-Blind (SSB) Wk 48-96
Participants in this arm received Placebo subcutaneous (sc) every 2 weeks from Week 48 onwards.
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 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 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 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.
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.
Regression, Logistic
<0.001
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.
Odds Ratio (OR)
14.069
2-Sided
95
7.395
27.955
Superiority
736
Title
Denominators
Categories
Title
Measurements
OG00043.9(40.3 to 47.6)
Units
Counts
Participants
OG000736
Title
Denominators
Categories
ASDAS-ID
Title
Measurements
OG00052.5
ASDAS-MD
Title
Measurements
OG00022.8
ASDAS-HD
Title
Measurements
OG00018.9
ASDAS-vHD
Title
Measurements
OG0005.9
Units
Counts
Participants
OG000736
Title
Denominators
Categories
ASDAS-CII
Title
Measurements
OG00076.6
ASDAS-MI
Title
Measurements
OG00056.1
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.
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG000113(84 to 257)
OG001371(371 to 371)
OG002NA(NA to NA)Values were not calculated since more than 75 % failed to meet the flare condition.
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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).
Log Rank
<0.001
Other
OG000
OG002
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).
Log Rank
<0.001
Other
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
ASDAS-ID
Title
Measurements
OG00058.3
OG00186.2
OG00269.9
ASDAS-MD
Title
Measurements
OG00025.0
OG00113.8
OG00222.9
ASDAS-HD
Title
Measurements
OG00016.7
OG0010
OG0027.2
ASDAS-vHD
Title
Measurements
OG0000
OG0010
OG0020
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
ASDAS-CII
Title
Measurements
OG00021.2
OG00182.7
OG00275.2
ASDAS-MI
Title
Measurements
OG00010.6
OG00167.3
OG00258.1
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
Regression, Logistic
<0.001
Odds Ratio (OR)
17.940
2-Sided
95
8.950
35.961
Superiority
OG000
OG002
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.
Regression, Logistic
<0.001
Odds Ratio (OR)
11.385
2-Sided
95
5.952
21.778
Superiority
OG000
OG001
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.
Regression, Logistic
<0.001
Odds Ratio (OR)
17.653
2-Sided
95
8.333
37.399
Superiority
OG000
OG002
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.
Regression, Logistic
<0.001
Odds Ratio (OR)
11.863
2-Sided
95
5.670
24.822
Superiority
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG00023.1
OG00185.6
OG00278.1
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
20.205
2-Sided
95
9.851
41.439
Superiority
OG000
OG002
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
12.070
2-Sided
95
6.275
23.218
Superiority
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG00021.2
OG00184.6
OG00273.3
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
20.891
2-Sided
95
10.210
42.744
Superiority
OG000
OG002
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
10.377
2-Sided
95
5.456
19.738
Superiority
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG00012.5
OG00170.2
OG00262.9
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
16.900
2-Sided
95
8.211
34.785
Superiority
OG000
OG002
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
12.072
2-Sided
95
5.954
24.476
Superiority
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG00017.3
OG00177.9
OG00270.5
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
17.082
2-Sided
95
8.561
34.085
Superiority
OG000
OG002
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
11.503
2-Sided
95
5.939
22.278
Superiority
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the RS.
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG0001.66± 0.110
OG0010.24± 0.077
OG0020.45± 0.077
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
Mixed Models Analysis
<0.001
LS Mean Difference vs Placebo
-1.42
Standard Error of the Mean
0.126
2-Sided
95
-1.66
-1.17
Other
OG000
OG002
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.
Mixed Models Analysis
<0.001
LS Mean Difference vs Placebo
-1.21
Standard Error of the Mean
0.126
2-Sided
95
-1.45
-0.96
Other
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG0003.02± 0.226
OG0010.56± 0.176
OG0020.78± 0.176
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
Mixed Models Analysis
<0.001
LS Mean Difference vs Placebo
-2.46
Standard Error of the Mean
0.268
2-Sided
95
-2.99
-1.94
Other
OG000
OG002
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.
Mixed Models Analysis
<0.001
LS Mean Difference vs Placebo
-2.24
Standard Error of the Mean
0.267
2-Sided
95
-2.77
-1.72
Other
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG0001.90± 0.233
OG0010.32± 0.198
OG0020.46± 0.205
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
Mixed Models Analysis
<0.001
LS Mean Difference vs Placebo
-1.57
Standard Error of the Mean
0.238
2-Sided
95
-2.04
-1.11
Other
OG000
OG002
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.
Mixed Models Analysis
<0.001
LS Mean Difference vs Placebo
-1.43
Standard Error of the Mean
0.238
2-Sided
95
-1.90
-0.96
Other
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG0000.21± 0.105
OG0010.00± 0.065
OG002-0.03± 0.068
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
Mixed Models Analysis
=0.074
LS Mean Difference vs Placebo
-0.20
Standard Error of the Mean
0.112
2-Sided
95
-0.42
0.02
Other
OG000
OG002
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.
Mixed Models Analysis
=0.036
LS Mean Difference vs Placebo
-0.24
Standard Error of the Mean
0.113
2-Sided
95
-0.46
-0.02
Other
Units
Counts
Participants
OG000104
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG00022.1
OG00183.7
OG00277.1
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
18.308
2-Sided
95
9.084
36.898
Superiority
OG000
OG002
Odds ratios (and corresponding p-values) were from a logistic regression model with factors for treatment group, geographical region, and mNY classification.
Regression, Logistic
<0.001
Odds Ratio (OR)
12.020
2-Sided
95
6.255
23.098
Superiority
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.
Units
Counts
Participants
OG00024
OG00179
OG00277
Title
Denominators
Categories
Title
Measurements
OG0001.1± 3.6
OG0010.2± 2.4
OG0020.6± 3.8
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
ANCOVA
=0.195
LS Mean Difference vs Placebo
-1.0
Standard Error of the Mean
0.76
2-Sided
95
-2.50
0.51
Other
OG000
OG002
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.
ANCOVA
=0.432
LS Mean Difference vs Placebo
-0.6
Standard Error of the Mean
0.76
2-Sided
95
-2.11
0.91
Other
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (RS)
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.
Units
Counts
Participants
OG00024
OG00179
OG00278
Title
Denominators
Categories
Title
Measurements
OG0000.4± 0.9
OG0010.0± 0.8
OG0020.0± 0.8
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
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.
ANCOVA
=0.040
LS Mean Difference vs Placebo
-0.4
Standard Error of the Mean
0.19
2-Sided
95
-0.78
-0.02
Other
OG000
OG002
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.
ANCOVA
=0.074
LS Mean Difference vs Placebo
-0.3
Standard Error of the Mean
0.19
2-Sided
95
-0.73
0.03
Other
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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.
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00073
OG0017
OG00215
Title
Denominators
Categories
ASDAS-ID
Title
Measurements
OG00063.4
OG00116.7
OG00260.0
ASDAS-MD
Title
Measurements
OG00026.8
OG00150.0
OG00220.0
ASDAS-HD
Title
Measurements
OG0008.5
OG00133.3
OG00220.0
ASDAS-vHD
Title
Measurements
OG0001.4
OG0010
OG0020
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.
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00073
OG0017
OG00215
Title
Denominators
Categories
ASDAS-CII
Title
Measurements
OG00084.5
OG00116.7
OG00246.7
ASDAS-MI
Title
Measurements
OG00049.3
OG0010
OG00213.3
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.
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00073
OG0017
OG00215
Title
Denominators
Categories
Title
Measurements
OG00083.3
OG00150.0
OG00264.3
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00073
OG0017
OG00215
Title
Denominators
Categories
Title
Measurements
OG00069.4
OG00116.7
OG00250.0
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00073
OG0017
OG00215
Title
Denominators
Categories
Title
Measurements
OG00060.6
OG00116.7
OG0027.1
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00073
OG0017
OG00215
Title
Denominators
Categories
Title
Measurements
OG00066.7
OG00116.7
OG00250.0
OG001
CZP 200 mg Q2W DB/CZP 200 mg Q2W Escape (FS)
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.
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00071
OG0016
OG00215
Title
Denominators
Categories
Title
Measurements
OG000-2.18± 1.13
OG001-0.56± 0.64
OG002-0.83± 0.94
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.
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00072
OG0016
OG00215
Title
Denominators
Categories
Title
Measurements
OG000-3.75± 2.52
OG001-1.55± 1.05
OG002-2.29± 2.35
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00072
OG0016
OG00214
Title
Denominators
Categories
Title
Measurements
OG000-2.52± 2.46
OG001-0.72± 0.70
OG002-1.83± 2.38
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.
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00067
OG0016
OG00215
Title
Denominators
Categories
Title
Measurements
OG000-0.43± 0.58
OG001-0.27± 0.35
OG002-0.26± 0.30
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00048
OG0012
OG00212
Title
Denominators
Categories
Title
Measurements
OG000-9.3± 13.2
OG0010.0± 0.0
OG0020.2± 3.1
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.
OG002
CZP 200 mg Q4W DB/CZP 200 mg Q2W Escape (FS)
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.
Units
Counts
Participants
OG00048
OG0012
OG00212
Title
Denominators
Categories
Title
Measurements
OG000-2.3± 4.6
OG0010.0± 0.0
OG002-0.3± 1.0
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (PKSB)
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.
Units
Counts
Participants
OG000101
OG001102
OG002105
Title
Denominators
Categories
Part A Baseline
ParticipantsOG00099
ParticipantsOG001101
ParticipantsOG002105
Title
Measurements
OG000NA± NAParticipants had no prior CZP treatment and thus no CZP levels at Baseline.
OG001NA± NAParticipants had no prior CZP treatment and thus no CZP levels at Baseline.
OG002NA± NAParticipants had no prior CZP treatment and thus no CZP levels at Baseline.
Week 4
ParticipantsOG000101
ParticipantsOG001100
ParticipantsOG002104
Title
Measurements
OG000
Week 12
ParticipantsOG000100
ParticipantsOG001101
ParticipantsOG002105
Title
Measurements
OG000
Week 24
ParticipantsOG000100
ParticipantsOG001101
ParticipantsOG002104
Title
Measurements
OG000
Week 48/Part B Baseline
ParticipantsOG00098
ParticipantsOG001100
ParticipantsOG002104
Title
Measurements
OG000
Week 60
ParticipantsOG00098
ParticipantsOG001100
ParticipantsOG002105
Title
Measurements
OG000
Week 72
ParticipantsOG00076
ParticipantsOG00195
ParticipantsOG00299
Title
Measurements
OG000
Week 84
ParticipantsOG00038
ParticipantsOG00191
ParticipantsOG00290
Title
Measurements
OG000
Week 96
ParticipantsOG00027
ParticipantsOG00186
ParticipantsOG00285
Title
Measurements
OG000
Withdrawal Visit
ParticipantsOG0004
ParticipantsOG0013
ParticipantsOG0025
Title
Measurements
OG000
Escape Week 0/Flare Baseline
ParticipantsOG00072
ParticipantsOG0016
ParticipantsOG00214
Title
Measurements
OG000
Escape Week 2
ParticipantsOG00071
ParticipantsOG0016
ParticipantsOG00215
Title
Measurements
OG000
Escape Week 4
ParticipantsOG00071
ParticipantsOG0016
ParticipantsOG00215
Title
Measurements
OG000
Escape Week 12
ParticipantsOG00069
ParticipantsOG0016
ParticipantsOG00215
Title
Measurements
OG000
Escape Week 24
ParticipantsOG00054
ParticipantsOG0013
ParticipantsOG0028
Title
Measurements
OG000
Escape Week 36
ParticipantsOG00014
ParticipantsOG0013
ParticipantsOG0023
Title
Measurements
OG000
Last Visit (Week 96)
ParticipantsOG00066
ParticipantsOG0016
ParticipantsOG00214
Title
Measurements
OG000
Withdrawal Escape Visit
ParticipantsOG0004
ParticipantsOG0011
ParticipantsOG0020
Title
Measurements
OG000
Safety Follow-up
ParticipantsOG00092
ParticipantsOG00192
ParticipantsOG00298
Title
Measurements
OG000
Participants in this arm received certolizumab pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.
Participants formed the PKSB.
OG002
Certolizumab Pegol 200 mg Q4W Double-Blind (PKSB)
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 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.
Units
Counts
Participants
OG000103
OG001104
OG002105
Title
Denominators
Categories
Title
Measurements
OG00054.4
OG00157.7
OG00261.0
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 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.
Units
Counts
Participants
OG00072
OG0016
OG00215
Title
Denominators
Categories
Title
Measurements
OG00051.4
OG00183.3
OG00246.7
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected15 at risk
12 events
11 affected
105 at risk
EG0047 events5 affected72 at risk
EG0051 events1 affected6 at risk
EG0061 events1 affected15 at risk
6 events
6 affected
105 at risk
EG0042 events2 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
1 events
1 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0052 events1 affected6 at risk
EG0060 events0 affected15 at risk
2 events
2 affected
105 at risk
EG0041 events1 affected72 at risk
EG0053 events1 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected15 at risk
1 events
1 affected
105 at risk
EG0043 events2 affected72 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected15 at risk
3 events
3 affected
105 at risk
EG0041 events1 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
1 events
1 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
2 events
1 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
2 events
2 affected
105 at risk
EG0041 events1 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
2 events
2 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected15 at risk
0 events
0 affected
105 at risk
EG0040 events0 affected72 at risk
EG0051 events1 affected6 at risk
EG0060 events0 affected15 at risk
2 events
2 affected
105 at risk
EG0040 events0 affected72 at risk
EG0050 events0 affected6 at risk
EG0061 events1 affected15 at risk
48.71
± 85.76
OG00153.39± 30.93
OG00248.92± 43.17
30.91
± 89.23
OG00131.74± 50.79
OG00230.69± 56.82
26.31
± 135.58
OG00130.23± 46.57
OG00228.96± 58.38
36.28
± 74.18
OG00136.59± 84.36
OG00231.11± 138.29
NA
± NA
Values were below the level of detection.
OG00127.76± 49.47
OG0026.95± 178.27
NA
± NA
Values were below the level of detection.
OG00126.36± 105.58
OG0027.61± 176.39
NA
± NA
Values were below the level of detection.
OG00126.57± 44.90
OG0028.00± 113.48
NA
± NA
Values were below the level of detection.
OG00124.76± 97.60
OG0027.16± 131.76
0.81
± 1802.40
OG001NA± NAValues were below the level of detection.
OG0020.30± 2621.06
NA
± NA
Values were below the level of detection.
OG00130.77± 19.78
OG00212.70± 98.45
18.27
± 488.45
OG00133.50± 21.17
OG00215.43± 124.10
37.32
± 151.18
OG00132.94± 30.48
OG00218.43± 79.93
23.89
± 232.36
OG00123.76± 65.42
OG00219.14± 136.22
27.47
± 45.31
OG001NA± NAValues were below the level of detection.
OG00219.23± 66.68
24.88
± 77.53
OG001NA± NAValues were below the level of detection.
OG002NA± NAValues were below the level of detection.
24.64
± 112.75
OG00126.19± 54.74
OG00218.59± 95.75
4.71
± 133329.3
OG001NA± NAValues were below the level of detection.