A Study to Test the Efficacy and Safety of Bimekizumab in the Treatment of Subjects With Active Psoriatic Arthritis

The HAQ-DI contains 20 items that measured the degree of difficulty experienced in the following 8 categories of the daily living activities: dressing and grooming (2 items), arising (2 items), eating (3 items), walking (2 items), hygiene (3 items), reach (2 items), grip (3 items), and common daily activities (3 items). Each question was scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). The overall HAQ-DI total score was calculated by dividing the sum of the highest category scores (0 to 24) by the number of categories with at least 1 question answered. The HAQ-DI total score ranges from 0 (no difficulty) to 3 (maximum difficulty). A lower HAQ-DI score indicated an improvement in function. Change from baseline was computed as the value at Week 16 minus the baseline value. A negative value in change from baseline indicated an improvement.

The PASI90 response assessments are based on at least 90% improvement in PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI = average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of respective section, and weighted by the percentage of the person's affected skin for respective section. The minimum possible PASI score is 0 = no disease, the maximum score is 72 = maximal disease.

The PASI90 response assessments are based on at least 90% improvement in PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI = average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of respective section, and weighted by the percentage of the person's affected skin for respective section. The minimum possible PASI score is 0 = no disease, the maximum score is 72 = maximal disease.

SF-36 (version 2, standard recall):36-item generic health-related Quality of Life instrument that uses recall period of 4 weeks. Questionnaire has 36 questions composing scale that represent 8 domains:physical functioning; role physical; bodily pain;general health;vitality; social functioning;role emotional; and mental health. Scores for 8 domains were combined into two summary scores: physical component summary (PCS) score and mental component summary (MCS) score. Scores for 2 components summary (PCS and MCS) and 8 domains have been calculated and computed as raw/observed score to norm-based T-score metric(mean=50, standard deviation=10), raw score min=0(worst), max=100(best). Individual respondent's score falls outside T-score range of 45 to 55 was considered outside average range and when considering group-level data, score below 47 was considered indicative of impaired functioning within that health domain or dimension. Positive value in change from Baseline indicated improvement.

MDA is measure to indicate disease remission, and is based on composite score of 7 domains. Participant is considered having achieved MDA if participant fulfills at least 5 of following 7 criteria: Tender joint count (0-68 joints) less than or equal to (≤1); Swollen joint count (0-66 joints) ≤ 1; PASI ≤ 1 or BSA ≤ 3: In PASI, body divided into four parts, head and neck, upper limb, trunk and lower limbs. Each area assessed for erythema, induration and scaling, each rated on a scale of 0 to 4. Total score ranges from 0(no disease) to 72 (maximal disease)]; Patient's Assessment of Arthritis Pain ≤ 15 [using VAS on a scale of 0 (no pain) to 100 (severe pain)]; Patient's Global Assessment of Disease Activity ≤ 20 [using VAS on a scale of 0 (very well) to 100 (very poor)]; HAQ-DI score ≤ 0.5, HAQ-DI score ranges from 0 (no difficulty) to 3 (maximum difficulty); Leeds Enthesitis Index score ≤ 1 for participants with enthesitis at baseline.

The degree of joint damage was assessed using the vdHmTSS by quantifying the extent of bone erosions and joint space narrowing for 64 and 52 joints, respectively. The vdHmTSS ranges from 0 to 528, with higher scores representing greater damage. Descriptive statistics for ADA 40 mg reference arm was not calculated and reported since reference based imputation analysis method is used with Placebo as reference. As pre-specified in the SAP, this analysis was performed only for the participants randomized to Placebo and BKZ.

Presence of enthesitis was assessed in the subgroup of participants with enthesitis by palpation on the lateral epicondyles of the humerus (elbows), medial femoral epicondyles (knees), and Achilles tendons (heels) bilaterally and scored as 0 (no tenderness) and 1 (tenderness) at Baseline. The LEI consists of 6 items, 3 for the right part and 3 for the left part of the body. LEI is derived as the sum of the enthesitis score over the 6 sites mentioned above. The total score ranges from 0 to 6, higher scores indicates greater degree of enthesitis. Descriptive/Inferential statistics for ADA 40 mg reference arm was not calculated and reported since pooled data with PA0011 study is used which did not have ADA 40 mg arm.

The LDI quantitatively measures dactylitis using the circumference of involved digits and control digits and tenderness of involved digits. Digits affected by dactylitis are defined as those with a 10% difference in the ratio of circumference of the affected digit to the contralateral digit. The control digit is either the contralateral digit (digit on opposite hand or foot). The ratio of circumference between an affected digit and the control digit is multiplied by the tenderness score for the affected digit. The results from each involved digit are summed to provide the final LDI score. A higher LDI indicates worse dactylitis. Tenderness score (0 = no tenderness, 1 = tender). Descriptive/Inferential statistics for ADA 40 mg reference arm was not calculated and reported since pooled data with PA0011 study was used which did not have ADA 40 mg arm.

The ACR20 response rate was based on a 20% or greater improvement of arthritis relative to Baseline. Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity (100 mm VAS [0 = no symptoms; 100 = severe symptoms]), Patient global assessment of disease activity (100 mm VAS [0 = no limitation of normal activities; 100 = very poor]), Patient assessment of pain (100 mm VAS [0 = no pain; 100 = most severe pain]), HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, lower scores indicated less disability, hsCRP.

The degree of joint damage was assessed using the vdHmTSS by quantifying the extent of bone erosions and joint space narrowing for 64 and 52 joints, respectively. The vdHmTSS ranges from 0 to 448, with higher scores representing greater damage. Descriptive statistics for ADA 40 mg reference arm was not calculated and reported since reference based imputation analysis method was used with Placebo as reference.

The ACR70 response rate was based on a 70% or greater improvement of arthritis relative to Baseline. Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria: 1. ≥ 70% improvement in 68-tender joint count; 2. ≥ 70% improvement in 66-swollen joint count; and 3. ≥ 70% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity (100 mm VAS [0 = no symptoms;100 = severe symptoms]), Patient global assessment of disease activity (100 mm VAS [0 = no limitation of normal activities;100 = very poor]), Patient assessment of pain (100 mm VAS [0 = no pain; 100 = most severe pain]), HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, lower scores indicated less disability, hsCRP.

IGA measured the overall severity of PSO using the following 5-point scale and score was rated as 0 = clear (No signs of PSO; post-inflammatory hyperpigmentation may be present), 1 = almost clear (No thickening; normal to pink coloration; no to minimal focal scaling), 2 = mild (Just detectable to mild thickening; pink to light red coloration; predominately fine scaling), 3 = moderate (Clearly distinguishable to moderate thickening; dull to bright red, moderate scaling), and 4 = severe (Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions). The IGA response is defined as score of 0 (clear) or 1 (almost clear) with at least a 2-category improvement relative to Baseline.

IGA measured the overall severity of PSO using the following 5-point scale and score was rated as 0 = clear (No signs of PSO; post-inflammatory hyperpigmentation may be present), 1 = almost clear (No thickening; normal to pink coloration; no to minimal focal scaling), 2 = mild (Just detectable to mild thickening; pink to light red coloration; predominately fine scaling), 3 = moderate (Clearly distinguishable to moderate thickening; dull to bright red, moderate scaling), and 4 = severe (Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions). The IGA response is defined as score of 0 (clear) or 1 (almost clear) with at least a 2-category improvement relative to Baseline.

The PtAAP VAS is part of the American College of Rheumatology core set of measures in arthritis. Participants assessed their arthritis pain using a VAS ranging from 0 (no pain) to 100 (most severe pain). A negative change from baseline indicates improvement.

Presence of enthesitis was assessed in the subgroup of participants with enthesitis at Baseline. The SPARCC index measures the severity of enthesitis through the assessment of 16 sites, 8 for the right part and 8 for the left part of the body: the greater trochanter (right/left), quadriceps tendon insertion into the patella (right/left), patellar ligament insertion into the patella and tibial tuberosity (right/left), achilles tendon insertion (right/left), plantar fascia insertion (right/left), medial and lateral epicondyles (right/left), and the supraspinatus insertion (right/left). Tenderness on examination is recorded as either present (1) or absent (0) for each of the 16 sites, for an average range of 0 (no enthesitis) to 16 (severe enthesitis).

The PsAID-12 is a patient-reported outcome measure for assessing the impact of Psoriatic Arthritis (PsA) in 12 physical and psychological domains, including pain, fatigue, skin problems, work and/or leisure activities, functional capacity, discomfort, sleep disturbance, coping, anxiety/fear/uncertainty, embarrassment and/or shame, social participation, and depression. Each domain is assessed with a single question using a 0 to 10 numerical rating scale. Each domain score was multiplied by a weighting factor and the results were then summed to provide the total score. The total score ranged from 0 to 10, with higher scores indicating a worse status. A negative change from baseline indicates improvement.

An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participants administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs were defined as any AEs with an onset date on or after the date of first IMP administration and within 140 days after the final dose of IMP.

A SAE is any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in patient hospitalization or prolongation of existing hospitalization; is a congenital anomaly or birth defect; is an infection that requires treatment parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. TEAEs were defined as any AEs with an onset date on or after the date of first IMP administration and within 140 days after the final dose of IMP.

An AE is any untoward medical occurrence in a patient or clinical investigation participants administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs were defined as any AEs with an onset date on or after the date of first IMP administration and within 140 days after the final dose of IMP.