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

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.

Time frame: 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).

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.

Time frame: 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.

Time frame: 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 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.

Time frame: 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.

Time frame: 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.

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.

Time frame: 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.

Time frame: 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.

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.

Time frame: 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.

Time frame: 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 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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 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.

Time frame: 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.

Time frame: 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 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.

Time frame: 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 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.

Time frame: 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 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.

Time frame: 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 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.

Time frame: 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.

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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 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.

Time frame: 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.

Time frame: Week 96

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

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.

Time frame: 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.

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)

Time frame: 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)

Time frame: 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.