Trial Outcomes & Findings for A Study to Assess the Effects of Certolizumab Pegol on the Reduction of Anterior Uveitis (AU) Flares in Axial Spondyloarthritis Subjects With a Documented History of AU (NCT NCT03020992)

Results Overview

A flare was defined as being a new episode of Anterior Uveitis (AU) that, based on the judgment of an ophthalmologist, required specific treatment. A flare was considered a new episode if a gap of at least 3 months occurred between 2 flares.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

89 participants

Primary outcome timeframe

During the pre-study period and during the Treatment Period up to 96 weeks

Results posted on

2021-02-09

Participant Flow

The first participant was enrolled in December 2016 and the last participant was enrolled in December 2017.

The study included 3 periods as follows: Period 1 (Screening Period) 1 to 5 weeks before Baseline, Period 2 (Treatment Period) Week 0 to Week 96 and Period 3 (FU Period) 10 weeks from the final dose of investigational medicinal product (IMP) received (Week 104). Participant Flow refers to the Safety Set.

Participant milestones

Participant milestones
Measure	Certolizumab Pegol Participants received a loading dose of Certolizumab Pegol (CZP) 400 milligrams (mg) subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc every 2 weeks (Q2W) (starting at Week 6 until Week 94).
Overall Study STARTED	89
Overall Study COMPLETED	83
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Certolizumab Pegol Participants received a loading dose of Certolizumab Pegol (CZP) 400 milligrams (mg) subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc every 2 weeks (Q2W) (starting at Week 6 until Week 94).
Overall Study Adverse Event	5
Overall Study Withdrawal by Subject	1

Baseline Characteristics

A Study to Assess the Effects of Certolizumab Pegol on the Reduction of Anterior Uveitis (AU) Flares in Axial Spondyloarthritis Subjects With a Documented History of AU

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Certolizumab Pegol n=89 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 milligrams (mg) subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc every 2 weeks (Q2W) (starting at Week 6 until Week 94).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	84 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Age, Continuous	46.52 years STANDARD_DEVIATION 11.24 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants
Race/Ethnicity, Customized White	87 Participants n=5 Participants
Race/Ethnicity, Customized Other or Mixed	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: During the pre-study period and during the Treatment Period up to 96 weeks

Population: The Full Analysis Set (FAS) consisted of all study participants in the Safety Set (SS) with nonmissing Baseline values for the primary efficacy variable (AU flare incidence data from the prestudy period).

A flare was defined as being a new episode of Anterior Uveitis (AU) that, based on the judgment of an ophthalmologist, required specific treatment. A flare was considered a new episode if a gap of at least 3 months occurred between 2 flares.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=89 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Number of Distinct Episodes of Anterior Uveitis (AU) Flares During the Treatment Period Pre-study Historical	1.9 flares Standard Deviation 0.9
Number of Distinct Episodes of Anterior Uveitis (AU) Flares During the Treatment Period On-study CZP	0.3 flares Standard Deviation 0.7

SECONDARY outcome

Timeframe: During the pre-study period and during the Treatment Period up to 48 weeks

Population: The Full Analysis Set (FAS) consisted of all study participants in the Safety Set (SS) with nonmissing Baseline values for the primary efficacy variable (AU flare incidence data from the prestudy period).

A flare was defined as being a new episode of Anterior Uveitis (AU) that, based on the judgment of an ophthalmologist, required specific treatment. A flare was considered a new episode if a gap of at least 3 months occurred between 2 flares.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=89 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Number of Anterior Uveitis (AU) Flares Per 100 Patient-years in Participants With Active Axial SpondyloArthritis (axSpA) and a History of AU at Week 48 Pre-study Historical	132.72 flares Interval 109.76 to 159.06
Number of Anterior Uveitis (AU) Flares Per 100 Patient-years in Participants With Active Axial SpondyloArthritis (axSpA) and a History of AU at Week 48 On-study CZP	18.56 flares Interval 10.39 to 30.61

SECONDARY outcome

Timeframe: During the pre-study period and during the Treatment Period up to 96 weeks

Population: The Full Analysis Set (FAS) consisted of all study participants in the Safety Set (SS) with nonmissing Baseline values for the primary efficacy variable (AU flare incidence data from the prestudy period).

A flare was defined as being a new episode of Anterior Uveitis (AU) that, based on the judgment of an ophthalmologist, required specific treatment. A flare was considered a new episode if a gap of at least 3 months occurred between 2 flares.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=89 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Number of Anterior Uveitis (AU) Flares Per 100 Patient-years in Participants With Active Axial SpondyloArthritis (axSpA) and a History of AU at Week 96 Pre-study Historical	97.51 flares Interval 83.24 to 113.53
Number of Anterior Uveitis (AU) Flares Per 100 Patient-years in Participants With Active Axial SpondyloArthritis (axSpA) and a History of AU at Week 96 On-study CZP	17.67 flares Interval 11.74 to 25.53

SECONDARY outcome

Timeframe: During the pre-study period and during the Treatment Period up to 48 weeks

Population: The Full Analysis Set (FAS) consisted of all study participants in the Safety Set (SS) with nonmissing Baseline values for the primary efficacy variable (AU flare incidence data from the prestudy period).

A flare was defined as being a new episode of Anterior Uveitis (AU) that, based on the judgment of an ophthalmologist, required specific treatment. A flare was considered a new episode if a gap of at least 3 months occurred between 2 flares.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=89 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Number of Anterior Uveitis (AU) Flares Per 100 Patient-years in Participants With Active Axial SpondyloArthritis (axSpA) and at Least 1 AU Episode Within 12 Months Prior Baseline at Week 48 Pre-study Historical	132.72 flares Interval 109.76 to 159.06
Number of Anterior Uveitis (AU) Flares Per 100 Patient-years in Participants With Active Axial SpondyloArthritis (axSpA) and at Least 1 AU Episode Within 12 Months Prior Baseline at Week 48 On-study CZP	18.56 flares Interval 10.39 to 30.61

SECONDARY outcome

Timeframe: During the pre-study period and during the Treatment Period up to 96 weeks

Population: The Full Analysis Set (FAS) consisted of all study participants in the Safety Set (SS) with nonmissing Baseline values for the primary efficacy variable (AU flare incidence data from the prestudy period).

A flare was defined as being a new episode of Anterior Uveitis (AU) that, based on the judgment of an ophthalmologist, required specific treatment. A flare was considered a new episode if a gap of at least 3 months occurred between 2 flares.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=89 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Number of Anterior Uveitis (AU) Flares Per 100 Patient-years in Participants With Active Axial SpondyloArthritis (axSpA) and at Least 1 AU Episode Within 12 Months Prior Baseline at Week 96 Pre-study Historical	97.51 flares Interval 83.24 to 113.53
Number of Anterior Uveitis (AU) Flares Per 100 Patient-years in Participants With Active Axial SpondyloArthritis (axSpA) and at Least 1 AU Episode Within 12 Months Prior Baseline at Week 96 On-study CZP	17.67 flares Interval 11.74 to 25.53

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set (ES) who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing ASDAS at Week 48.

The ASDAS was calculated as the sum of the following: 0.121 × Back pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result) 0.058 × Duration of morning stiffness (BASDAI Question 6 result) 0.110 × Patient's Global Assessment of Disease Activity (PtGADA) 0.073 × Peripheral pain/swelling (BASDAI Question 3 result) 0.579 × (natural logarithm (C-Reactive Protein (CRP) \[mg/L\] + 1)) Back pain, PtGADA, duration of morning stiffness, and peripheral pain/swelling are all assessed on a numerical scale (0 to 10 units). The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. 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.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 48	-1.55 scores on a scale Standard Deviation 1.03

SECONDARY outcome

Timeframe: From Baseline to Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing ASDAS at Week 96.

The ASDAS was calculated as the sum of the following: 0.121 × Back pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result) 0.058 × Duration of morning stiffness (BASDAI Question 6 result) 0.110 × Patient's Global Assessment of Disease Activity (PtGADA) 0.073 × Peripheral pain/swelling (BASDAI Question 3 result) 0.579 × (natural logarithm (C-Reactive Protein (CRP) \[mg/L\] + 1)) Back pain, PtGADA, duration of morning stiffness, and peripheral pain/swelling are all assessed on a numerical scale (0 to 10 units). The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. 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.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96	-1.61 scores on a scale Standard Deviation 1.08

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing BASDAI at Week 48.

The BASDAI is a validated self-reported instrument which consists of 6 horizontal Numeric Rating Scales (NRSs), each with 10 units to measure the severity of the 5 major symptoms: fatigue, spinal pain, peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. To give each symptom equal weighting, the average of the 2 scores relating to morning stiffness is taken. The resulting 0 to 50 sum score is divided by 5 to give a final BASDAI score between 0 and 10, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 48	-3.2 scores on a scale Standard Deviation 2.3

SECONDARY outcome

Timeframe: From Baseline to Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing BASDAI at Week 96.

The BASDAI is a validated self-reported instrument which consists of 6 horizontal Numeric Rating Scales (NRSs), each with 10 units to measure the severity of the 5 major symptoms: fatigue, spinal pain, peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. To give each symptom equal weighting, the average of the 2 scores relating to morning stiffness is taken. The resulting 0 to 50 sum score is divided by 5 to give a final BASDAI score between 0 and 10, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96	-3.4 scores on a scale Standard Deviation 2.2

SECONDARY outcome

Timeframe: Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Percentages were based on the number of participants with an assessment at Week 48.

The ASAS20 is 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 following domains and absence of deterioration in the potential remaining domain \[deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit\]: * Patient's Global Assessment of Disease Activity (PtGADA) * Pain assessment (the total spinal pain Numeric Rating Scale score) * Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) * Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Percentage of Participants Meeting Assessment of SpondyloArthritis International Society 20 % Response Criteria (ASAS20) at Week 48	75.6 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Percentages were based on the number of participants with an assessment at Week 96.

The ASAS20 is 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 following domains and absence of deterioration in the potential remaining domain \[deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit\]: * Patient's Global Assessment of Disease Activity (PtGADA) * Pain assessment (the total spinal pain Numeric Rating Scale score) * Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) * Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Percentage of Participants Meeting Assessment of SpondyloArthritis International Society 20 % Response Criteria (ASAS20) at Week 96	75.6 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Percentages were based on the number of participants with an assessment at Week 48.

The ASAS criteria for 40 % improvement were defined as relative improvements 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 below and no worsening at all in the remaining domain: * Patient's Global Assessment of Disease Activity (PtGADA) * Pain assessment (the total spinal pain Numeric Rating Scale score) * Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) * Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Percentage of Participants Meeting Assessment of SpondyloArthritis International Society 40 % Response Criteria (ASAS40) at Week 48	53.5 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Percentages were based on the number of participants with an assessment at Week 96.

The ASAS criteria for 40 % improvement were defined as relative improvements 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 below and no worsening at all in the remaining domain: * Patient's Global Assessment of Disease Activity (PtGADA) * Pain assessment (the total spinal pain Numeric Rating Scale score) * Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) * Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Percentage of Participants Meeting Assessment of SpondyloArthritis International Society 40 % Response Criteria (ASAS40) at Week 96	58.5 percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: Data not collected from participants in all Arms/Groups.

The ASAS 5/6 response is defined as at least 20 % improvement in 5 of 6 domains, including spinal mobility (lateral spinal flexion) and C-Reactive Protein (CRP) as more objective measures. As the BASMI was not collected, and there was no alternative measure of spinal mobility available in the study data, the complete component for spinal mobility was missing. Therefore the ASAS 5/6 response criterion cannot be calculated, and the analysis of the secondary efficacy variable ASAS 5/6 had to be dropped.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 96

Population: Data not collected from participants in all Arms/Groups.

The ASAS 5/6 response is defined as at least 20 % improvement in 5 of 6 domains, including spinal mobility (lateral spinal flexion) and C-Reactive Protein (CRP) as more objective measures. As the BASMI was not collected, and there was no alternative measure of spinal mobility available in the study data, the complete component for spinal mobility was missing. Therefore the ASAS 5/6 response criterion cannot be calculated, and the analysis of the secondary efficacy variable ASAS 5/6 had to be dropped.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Percentages were based on the number of participants with an assessment at Week 48.

The ASAS PR response is defined as a score of ≤2 units on a 0 to 10 unit scale in all of the 4 following domains: * Patient's Global Assessment of Disease Activity (PtGADA) * Pain assessment (the total spinal pain Numeric Rating Scale score) * Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) * Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response at Week 48	31.4 percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Percentages were based on the number of participants with an assessment at Week 96.

The ASAS PR response is defined as a score of ≤2 units on a 0 to 10 unit scale in all of the 4 following domains: * Patient's Global Assessment of Disease Activity (PtGADA) * Pain assessment (the total spinal pain Numeric Rating Scale score) * Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI)) * Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration)

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response at Week 96	36.6 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with at least one tender joint count at Baseline (N=59) and had a non-missing tender joint count at Week 48 (N=55).

The following 44 joints were to be examined for swelling and tenderness by the Investigator, another delegated physician, or an appropriately qualified medical professional: * Upper body (4) - bilateral sternoclavicular and acromioclavicular joints * Upper extremity (26) - bilateral shoulders, elbows, wrists (includes radiocarpal, carpal, and carpometacarpal bones considered as a single unit), metacarpophalangeals (MCPs) I,II, III, IV, and V, and thumb interphalangeals (IPs), and proximal IPs (PIPs) II, III, IV, and V * Lower extremity (14) - bilateral knees, ankles, and metatarsophalangeals (I, II, III, IV, and V) The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=55 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Tender Joint Count (44 Joint Count) at Week 48	-4.9 tender joints Standard Deviation 6.7

SECONDARY outcome

Timeframe: From Baseline to Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with at least one tender joint count at Baseline (N=59) and had a non-missing tender joint count at Week 96 (N=51).

The following 44 joints were to be examined for swelling and tenderness by the Investigator, another delegated physician, or an appropriately qualified medical professional: * Upper body (4) - bilateral sternoclavicular and acromioclavicular joints * Upper extremity (26) - bilateral shoulders, elbows, wrists (includes radiocarpal, carpal, and carpometacarpal bones considered as a single unit), metacarpophalangeals (MCPs) I,II, III, IV, and V, and thumb interphalangeals (IPs), and proximal IPs (PIPs) II, III, IV, and V * Lower extremity (14) - bilateral knees, ankles, and metatarsophalangeals (I, II, III, IV, and V) The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=51 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Tender Joint Count (44 Joint Count) at Week 96	-4.7 tender joints Standard Deviation 8.2

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with at least one swollen joint count at Baseline (N=33) and had a non-missing swollen joint count at Week 48 (N=32).

The following 44 joints were to be examined for swelling and tenderness by the Investigator, another delegated physician, or an appropriately qualified medical professional: * Upper body (4) - bilateral sternoclavicular and acromioclavicular joints * Upper extremity (26) - bilateral shoulders, elbows, wrists (includes radiocarpal, carpal, and carpometacarpal bones considered as a single unit), metacarpophalangeals (MCPs) I,II, III, IV, and V, and thumb interphalangeals (IPs), and proximal IPs (PIPs) II, III, IV, and V * Lower extremity (14) - bilateral knees, ankles, and metatarsophalangeals (I, II, III, IV, and V) The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=32 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Swollen Joint Count (44 Joint Count) at Week 48	-4.2 swollen joints Standard Deviation 4.8

SECONDARY outcome

Timeframe: From Baseline to Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with at least one swollen joint count at Baseline (N=33) and had a non-missing swollen joint count at Week 96 (N=30).

The following 44 joints were to be examined for swelling and tenderness by the Investigator, another delegated physician, or an appropriately qualified medical professional: * Upper body (4) - bilateral sternoclavicular and acromioclavicular joints * Upper extremity (26) - bilateral shoulders, elbows, wrists (includes radiocarpal, carpal, and carpometacarpal bones considered as a single unit), metacarpophalangeals (MCPs) I,II, III, IV, and V, and thumb interphalangeals (IPs), and proximal IPs (PIPs) II, III, IV, and V * Lower extremity (14) - bilateral knees, ankles, and metatarsophalangeals (I, II, III, IV, and V) The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=30 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Swollen Joint Count (44 Joint Count) at Week 96	-3.9 swollen joints Standard Deviation 5.2

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing PhGADA at Week 48.

The Investigator assessed the overall status of the participant with respect to the axSpA signs and symptoms and the functional capacity of the participant using a Visual Analog Scale (VAS) where 0 is "very good, asymptomatic and no limitation of normal activities" and 100 is "very poor, very severe symptoms that are intolerable, and the inability to carry out all normal activities." This assessment by the Investigator should be made without any knowledge of the Patient's Global Assessment of Disease Activity (PtGADA). Total score ranges from 0 to 100, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Physician's Global Assessment of Disease Activity (PhGADA) at Week 48	-43.8 scores on a scale Standard Deviation 21.6

SECONDARY outcome

Timeframe: From Baseline to Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing PhGADA at Week 96.

The Investigator assessed the overall status of the participant with respect to the axSpA signs and symptoms and the functional capacity of the participant using a Visual Analog Scale (VAS) where 0 is "very good, asymptomatic and no limitation of normal activities" and 100 is "very poor, very severe symptoms that are intolerable, and the inability to carry out all normal activities." This assessment by the Investigator should be made without any knowledge of the Patient's Global Assessment of Disease Activity (PtGADA). Total score ranges from 0 to 100, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Physician's Global Assessment of Disease Activity (PhGADA) at Week 96	-42.5 scores on a scale Standard Deviation 27.1

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing PtGADA at Week 48.

For the PtGADA questionnaire, participants scored their global assessment of their disease activity in response to the question "How active was your spondylitis on average during the last week?" using a Numeric Rating Scale (NRS) where 0 was "not active" and 10 was "very active". Total score ranges from 0 to 10, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Patient's Global Assessment of Disease Activity (PtGADA) at Week 48	-3.6 scores on a scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: From Baseline to Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing PtGADA at Week 96.

For the PtGADA questionnaire, participants scored their global assessment of their disease activity in response to the question "How active was your spondylitis on average during the last week?" using a Numeric Rating Scale (NRS) where 0 was "not active" and 10 was "very active". Total score ranges from 0 to 10, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Patient's Global Assessment of Disease Activity (PtGADA) at Week 96	-3.9 scores on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing total spinal pain assessment at Week 48.

The total spinal pain was assessed with the question 'How much pain of your spine due to spondylitis do you have?' using a Numeric Rating Scale (NRS) where 0 was 'No pain' and 10 was 'Most severe pain'. Usually, a 10 % difference (ie, a 1 point difference on a Numeric Rating Scale (NRS) ranging from 0 to 10) is considered the minimal clinically important difference used to interpret scores (Dworkin et al, 2008). Total score ranges from 0 to 10, with lower scores indicating a worse outcome. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Total Spinal Pain at Week 48 Assessed by Numerical Rating Scale (NRS)	-3.8 scores on a scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: From Baseline to Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing total spinal pain assessment at Week 96.

The total spinal pain was assessed with the question 'How much pain of your spine due to spondylitis do you have?' using a Numeric Rating Scale (NRS) where 0 was 'No pain' and 10 was 'Most severe pain'. Usually, a 10 % difference (ie, a 1 point difference on a Numeric Rating Scale (NRS) ranging from 0 to 10) is considered the minimal clinically important difference used to interpret scores (Dworkin et al, 2008). Total score ranges from 0 to 10, with lower scores indicating a worse outcome. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline in Total Spinal Pain at Week 96 Assessed by Numerical Rating Scale (NRS)	-4.1 scores on a scale Standard Deviation 2.6

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing BASFI at Week 48.

The BASFI is a validated disease-specific instrument for assessing physical function (van Tubergen et al, 2015; Calin et al, 1994; van der Heijde et al, 2005). The BASFI comprises 10 items relating to the past week. The Numeric Rating Scale (NRS) version was used for the answering options of each item on a scale of 0 ("Easy") to 10 ("Impossible") (van Tubergen et al, 2002). The BASFI score is the mean of the 10 items such that the total score ranges from 0 to 10, with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline to Week 48 in the Bath Ankylosing Spondylitis Functional Index (BASFI)	-2.23 scores on a scale Standard Deviation 2.33

SECONDARY outcome

Timeframe: From Baseline to Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing BASFI at Week 96.

The BASFI is a validated disease-specific instrument for assessing physical function (van Tubergen et al, 2015; Calin et al, 1994; van der Heijde et al, 2005). The BASFI comprises 10 items relating to the past week. The Numeric Rating Scale (NRS) version was used for the answering options of each item on a scale of 0 ("Easy") to 10 ("Impossible") (van Tubergen et al, 2002). The BASFI score is the mean of the 10 items such that the total score ranges from 0 to 10, with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline to Week 96 in the Bath Ankylosing Spondylitis Functional Index (BASFI)	-2.28 scores on a scale Standard Deviation 2.53

SECONDARY outcome

Timeframe: From Baseline to Week 48

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing BASDAI at Week 48.

The BASDAI is a validated self-reported instrument which consists of six 10-unit horizontal Numeric Rating Scales (NRS) to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration for each disease activity, respectively) over the last week. The mean of the 2 BASDAI questions related to morning stiffness (questions 5 and 6) ranged from 0 to 10, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=86 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline to Week 48 in Inflammation Assessed by the Mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6 Concerning Morning Stiffness and Duration	-3.7 scores on a scale Standard Deviation 2.8

SECONDARY outcome

Timeframe: From Baseline to Week 96

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP. Number of participants analyzed reflect those with a non-missing BASDAI at Week 96.

The BASDAI is a validated self-reported instrument which consists of six 10-unit horizontal Numeric Rating Scales (NRS) to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration for each disease activity, respectively) over the last week. The mean of the 2 BASDAI questions related to morning stiffness (questions 5 and 6) ranged from 0 to 10, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=82 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Change From Baseline to Week 96 in Inflammation Assessed by the Mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6 Concerning Morning Stiffness and Duration	-3.8 scores on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: From Baseline up to the Safety Follow-up Visit (up to Week 104)

Population: The Safety Set consisted of all study participants in the Enrolled Set who had received at least 1 dose of IMP.

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Outcome measures

Outcome measures
Measure	Certolizumab Pegol (FAS) n=89 Participants Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Percentage of Participants Reporting at Least One Treatment-Emergent Adverse Events (TEAEs) During the Study	80.9 percentage of participants

Adverse Events

Certolizumab Pegol (SS)

Serious events: 11 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Certolizumab Pegol (SS) n=89 participants at risk Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Ear and labyrinth disorders Vestibular disorder	2.2% 2/89 • Number of events 2 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Eye disorders Uveitis	1.1% 1/89 • Number of events 2 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Gastrointestinal disorders Anal polyp	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
General disorders Incarcerated hernia	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Hepatobiliary disorders Cholelithiasis	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Immune system disorders Sarcoidosis	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Infections and infestations Pneumonia haemophilus	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Infections and infestations Pneumonia	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Musculoskeletal and connective tissue disorders Tenosynovitis	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	2.2% 2/89 • Number of events 2 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Pregnancy, puerperium and perinatal conditions Pregnancy	1.1% 1/89 • Number of events 1 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)

Other adverse events

Other adverse events
Measure	Certolizumab Pegol (SS) n=89 participants at risk Participants received a loading dose of Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) administered at Baseline, Week 2, and Week 4 followed by CZP 200 mg sc Q2W (starting at Week 6 until Week 94).
Eye disorders Uveitis	15.7% 14/89 • Number of events 23 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Eye disorders Iridocyclitis	9.0% 8/89 • Number of events 12 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Infections and infestations Nasopharyngitis	16.9% 15/89 • Number of events 22 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Infections and infestations Upper respiratory tract infection	13.5% 12/89 • Number of events 15 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Infections and infestations Influenza	6.7% 6/89 • Number of events 9 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Infections and infestations Rhinitis	6.7% 6/89 • Number of events 9 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Investigations Alanine aminotransferase increased	5.6% 5/89 • Number of events 5 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 6/89 • Number of events 7 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.6% 5/89 • Number of events 5 • Treatment emergent adverse events were collected from Baseline to the Safety Follow-up Visit (up to Week 104)

Additional Information

UCB

Cares

Phone: +1844 599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60