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.

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.

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.

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.

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.

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.

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.

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.

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.

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)

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)

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)

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)

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.

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.

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)

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)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.