Efficacy and Safety of BMS-986165 Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA)

The HAQ-DI is measured by the use of a patient-reported outcome measure questionnaire, assessing the degree of difficulty a person has experienced during the past week in 8 domains of daily living activities. Each activity category consists of 2 to 3 questions (total of 20 questions). For reach question the level of activity is scored from 0 to 3, with 0 representing "no difficulty" and 3 as "unable to do". Any activity that requires assistance from another individual or an assistive device adjusts to a minimum score of 2. For each activity category, the highest score reported in the 2 or 3 questions pertinent to that category represents the category score. Scores from the 8 categories are then summed and divided by 8 to generate the final score. The final score can range from 0 (most desirable outcome) to 3 (least desirable outcome). Adjusted change represents a change from baseline based on statistical model.

The PASI is a measure of the average erythema, induration thickness and scaling of psoriatic skin lesions (each graded on a 0 to 4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. The PASI 75 response rate represents the percentage of participants who experienced at least a 75% improvement in PASI score as compared with the baseline value. PASI assessment was performed by trained professionals.

The SF-36 is a patient-reported outcome measure, which includes 36 items in a Likert-type format to measure the following 8 health dimensions over the past week: 1) limitations in physical activities, such as bathing or dressing 2) limitations in social activities because of physical or emotional problems 3) limitations in usual role activities because of physical health problems 4) bodily pain 5) general mental health (psychological distress and well-being) 6) limitations in usual role activities because of emotional problems 7) vitality (energy and fatigue) and 8) general health perceptions. The 8 health dimensions assessed are grouped into 2 main components, physical and mental. Each of the 8 dimensions contribute to both the Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. PCS and MCS scores range from 0 to 100, with high scores indicating a better health status. Adjusted change represents a change from baseline based on statistical model.

A participant is considered an ACR 50 responder if the following three conditions are met: 1) ≥ 50% improvement from baseline in the number of tender joints (68 joint count). 2) ≥ 50% improvement from baseline in the number of swollen joints (66 joint count). 3) ≥ 50% improvement from baseline in at least 3 of the following 5 domains: o Subject Global Assessment of disease activity o Physician Global Assessment of psoriatic arthritis o Subject Global Assessment of pain o Health Assessment Questionnaire-Disability Index (HAQ-DI) o High-sensitivity C-reactive protein (hsCRP)

A participant is considered an ACR 70 responder if the following three conditions are met: 1) ≥ 70% improvement from baseline in the number of tender joints (68 joint count). 2) ≥ 70% improvement from baseline in the number of swollen joints (66 joint count). 3) ≥ 70% improvement from baseline in at least 3 of the following 5 domains: o Subject Global Assessment of disease activity o Physician Global Assessment of psoriatic arthritis o Subject Global Assessment of pain o Health Assessment Questionnaire-Disability Index (HAQ-DI) o High-sensitivity C-reactive protein (hsCRP)

A Disease Activity Score (DAS) is a scoring system used to assess disease activity. DAS 28 CRP is a composite outcome measure that assesses: • How many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints, but excluding distal interphalangeal joints), wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28. • C Reactive Protein (CRP) levels in the blood (as a measure of the degree of inflammation) • Subject Global Assessment of disease activity The results are combined to produce the DAS 28 CRP score, which correlates with the extent of disease activity as follows: • < 2.6: Disease remission • 2.6 - 3.2: Low disease activity • 3.2 - 5.1: Moderate disease activity • > 5.1: High disease activity. Only participants with a score < 3.2 are considered to have achieved low disease activity.

A Disease Activity Score (DAS) is a scoring system used to assess disease activity. DAS 28 CRP is a composite outcome measure that assesses: • How many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints, but excluding distal interphalangeal joints), wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28. • C Reactive Protein (CRP) levels in the blood (as a measure of the degree of inflammation) • Subject Global Assessment of disease activity The results are combined to produce the DAS 28 CRP score, which correlates with the extent of disease activity as follows: • < 2.6: Disease remission • 2.6 - 3.2: Low disease activity • 3.2 - 5.1: Moderate disease activity • > 5.1: High disease activity. Only participants with a score < 2.6 are considered to have achieved remission.

A Disease Activity Score (DAS) is a scoring system used to assess disease activity. DAS 28 CRP is a composite outcome measure that assesses: • How many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints, but excluding distal interphalangeal joints), wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28. • C Reactive Protein (CRP) levels in the blood (as a measure of the degree of inflammation) • Subject Global Assessment of disease activity The results are combined to produce the DAS 28 CRP score, which correlates with the extent of disease activity as follows: • < 2.6: Disease remission • 2.6 - 3.2: Low disease activity • 3.2 - 5.1: Moderate disease activity • > 5.1: High disease activity. Adjusted change represents a change from baseline based on statistical model.

The number of digits in hands and feet with dactylitis (Tender + Non-Tender) was counted and change from baseline at week 16 was assessed. Adjusted change represents a change from baseline based on statistical model.

The Leeds Dactylitis Index (LDI) Basic is a quantitative measurement of dactylitis in the 20 digits using a dactylometer. The circumference of the affected and contralateral digits, and tenderness of the affected digits are measured to generate a total score. For each dactylitic digit, the final score is defined as: [{(A/B) - 1}*100]*C, where A is circumference of involved digit, B is circumference of the opposite, unaffected, digit or reference, and C is tenderness (0 or 1). The total score is determined by summing the relative score of all digits. A higher score indicates worse dactylitis. Adjusted change represents a change from baseline based on statistical model.

Dactylitis resolution (tender digits only) is defined as a dactylitis count of 0 in participants with dactylitis count ≥ 1 at baseline

The LEI was developed specifically for psoriatic arthritis. An overall score of 0 to 6 is derived from the presence or absence of tenderness at 6 entheseal sites (right and left: lateral epicondyle, medial femoral condyle, and Achilles tendon insertion) at the time of evaluation. A higher count indicates a greater enthesitis burden. Adjusted change represents a change from baseline based on statistical model.

The SPARCC Enthesitis Index has a 0 to 16 score that is derived from the evaluation of 8 locations: the greater trochanter (R/L), quadriceps tendon insertion into the patella (R/L), patellar ligament insertion into the patella and tibial tuberosity (R/L), Achilles tendon insertion (R/L), plantar fascia insertion (R/L), medial and lateral epicondyles (R/L), and the supraspinatus insertion (R/L). A higher count indicates a higher enthesitis burden based on the current evaluation. Adjusted change represents a change from baseline based on statistical model.

The LEI was developed specifically for psoriatic arthritis. An overall score of 0 to 6 is derived from the presence or absence of tenderness at 6 entheseal sites (right and left: lateral epicondyle, medial femoral condyle, and Achilles tendon insertion) at the time of evaluation. A higher count indicates a greater enthesitis burden. Enthesitis resolution is defined as s LEI score of 0, in subjects with LEI ≥ 1 at baseline

The SPARCC Enthesitis Index has a 0 to 16 score that is derived from the evaluation of 8 locations: the greater trochanter (R/L), quadriceps tendon insertion into the patella (R/L), patellar ligament insertion into the patella and tibial tuberosity (R/L), Achilles tendon insertion (R/L), plantar fascia insertion (R/L), medial and lateral epicondyles (R/L), and the supraspinatus insertion (R/L). A higher count indicates a higher enthesitis burden based on the current evaluation. Enthesitis resolution defined as a SPARCC enthesitis index score of 0, in subjects with SPARCC ≥ 1 at baseline.

In participants with psoriasis fingernail involvement, the PGA-F score is used to evaluate the overall condition of the fingernails in terms of disease severity. The assessment is performed by the investigator, who rates the fingernail condition on a 5-point scale based on the higher of the nail bed/nail matrix score. Scores are 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe).

A Minimal Disease Activity (MDA) responder is defined as a participant fulfilling 5 of the following 7 outcomes: • Tender joint count ≤ 1 • Swollen joint count ≤ 1 • Psoriasis Area and Severity Index (PASI) ≤ 1 or body surface area (BSA) ≤ 3% • Subject Global Assessment of pain ≤ 15 • Subject Global Assessment of disease activity ≤ 20 • Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤ 0.5 • Tender entheseal points ≤ 1

PASDAS is a composite measure calculated from the Physician Global Assessment of psoriatic arthritis, the Subject Global Assessment of disease activity, the Short Form Health Survey-36 Item (SF-36) Physical Component Summary (PCS), the swollen joint count, the tender joint count, the Leeds Enthesitis Index (LEI), the Leeds Dactylitis Index (LDI) (Basic), and the the levels of high-sensitivity C-reactive Protein (hsCRP). Each item contributes differently to the final score, which ranges from 0 to 10 (higher scores represent a higher level of disease activity). Adjusted change represents a change from baseline based on statistical model.

DAPSA is a composite measure to assess peripheral joint involvement that is based upon numerical summation of 5 variables of disease activity: tender/painful joint count 68, swollen joint count 66, Subject Global Assessment of disease activity, Subject Global Assessment of pain, and the levels of C-reactive Protein (CRP). Final scores are interpreted as follows: - ≤4 = Remission (REM) - > 4 and ≤ 28 = moderate disease activity (MDA) - >28 = high disease activity (HDA). Adjusted change represents a change from baseline based on statistical model.

PsARC consists of 4 measurements: tender/painful joint count, swollen joint count, Physician Global Assessment of psoriatic arthritis, and Subject Global Assessment of pain ≤ 15. In order to be classified as a PsARC responder, participants must achieve improvement in 2 of 4 measures, one of which must be joint pain or swelling, without worsening in any measure.

In participants with baseline evidence of Psoriatic Arthritis Spondylitis, symptoms are evaluated using the BASDAI, which consists of a 0 to 100 scale measuring discomfort, pain, and fatigue in response to 6 questions pertaining to the 5 major symptoms of ankylosing spondylitis: • Fatigue (medical) • Spinal pain • Joint pain and swelling • Areas of localized tenderness • Morning stiffness duration • Morning stiffness severity A higher count indicates worse disease. Adjusted change represents a change from baseline based on statistical model.

The SF-36 is a patient-reported outcome measure, which includes 36 items in a Likert-type format to measure the following 8 health dimensions over the past week: 1) limitations in physical activities, such as bathing or dressing 2) limitations in social activities because of physical or emotional problems 3) limitations in usual role activities because of physical health problems 4) bodily pain 5) general mental health (psychological distress and well-being) 6) limitations in usual role activities because of emotional problems 7) vitality (energy and fatigue) and 8) general health perceptions. The 8 health dimensions assessed are grouped into 2 main components, physical and mental. Each of the 8 dimensions contribute to both the Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. PCS and MCS scores range from 0 to 100, with high scores indicating a better health status. Adjusted change represents a change from baseline based on statistical model.

PsAID is a 12-item self-report that measures psoriatic arthritis symptoms and impact of disease. Each item is scored on a 0 to 10 numeric rating scale, and each item contributes differently to the final score. Weighted scores for each item are summed and divided by 20 to generate the final score, ranging from 0 to 10 (higher values indicate worse health). Adjusted change represents a change from baseline based on statistical model.

The FACIT-Fatigue instrument is a questionnaire used to evaluate a range of self-reported symptoms over the past week, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. The questionnaire is composed of 13 questions (Short Form 13a) and each question is scored from 1 to 5. The final score results from the sum of the scores of the 13 questions, and ranges from 13 (most desirable outcome) to 65 (least desirable outcome). Adjusted change represents a change from baseline based on statistical model.

The Work Limitation Questionnaire (WLQ) is a 25-item self-report that measures the on-the-job impact of chronic health conditions and treatment over the past 2 weeks. It focuses on assessing limitations while performing specific job demands from the following 4 domains: 1) Time management: difficulty with handling time and scheduling demands (5 items) 2) Physical demands: ability to perform job tasks that involve bodily strength, movement, endurance, coordination, and flexibility (6 items) 3) Mental-interpersonal demands: cognitively demanding tasks and on-the-job social interactions (9 items) 4) Output demands: concerns reduced work productivity (5 items). Final score ranges from 0 (limited none of the time) to 100 (limited all of the time). The score can be used to calculate a percent of lost work productivity due to a particular disease state. Adjusted change represents a change from baseline based on statistical model.

The HAQ-DI is measured by the use of a patient-reported outcome measure questionnaire, assessing the degree of difficulty a person has experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2 to 3 questions (total of 20 questions). For reach question the level of activity is scored from 0 ("no difficulty") to 3 ("unable to do"). For each activity category, the highest score reported in the 2 or 3 questions pertinent to that category represents the category score. Scores from the 8 categories are then summed and divided by 8 to generate the final score. The final score can range from 0 (most desirable outcome) to 3 (least desirable outcome). A HAQ-DI 0.35 responder is defined as a participant with an improvement from baseline in HAQ-DI score of at least 0.35.

The PASI is a measure of the average erythema, induration thickness and scaling of psoriatic skin lesions (each graded on a 0 to 4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. The PASI 90 response rate represents the percentage of participants who experienced at least a 90% improvement in PASI score as compared with the baseline value. PASI assessment was performed by trained professionals.