A Study to Determine the Efficacy and Safety of Deucravacitinib Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had Previously Received TNFα Inhibitor Treatment

DAS28-CRP is a composite of how many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints but excluding DIPs), wrists, elbows, shoulders, and knees are swollen and/or tender out of a total of 28; CRP in the blood to measure the degree of inflammation, and participant global assessment of disease activity. The results are combined to produce the DAS28-CRP score that range from 1.0 to 9.4, which correlates with the extent of disease activity: < 2.6=disease remission; 2.6 - 3.2=low disease activity; 3.2-5.1=moderate disease activity; >5.1=high disease activity. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in DAS28-CRP indicates an improvement.

HAQ-DI is a patient-reported outcome measure that assesses the degree of difficulty a participant 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 items. For each item in the questionnaire, the level of activity is scored from 0 to 3, with 0 representing "no difficulty," 1 representing "some difficulty," 2 representing "much difficulty," and 3 representing "unable to do." increasing scores for the 8 disability categories indicate increasing level of difficulty. HAQDI is calculated by summing the adjusted categories scores and dividing by the number of categories answered. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in HAQ-DI indicates an improvement.

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. PASI 75 is the number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value. Baseline is defined as the last measurement on or prior to date/time of first dose of study treatment.

SF-36 is a generic 36-item questionnaire measuring health-related quality of life. The physical component summary (PCS) consists of these 4 subscales: Physical functioning, Role-physical, Bodily pain, General health. The scores range from 0 to 100, with a higher score indicating better quality of life. The PCS summary scores will be calculated by taking a weighted linear combination of the individual subscales. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in SF-36 PCS indicates an improvement.

Number of participants meeting enthesitis resolution (score of 0) among participants with enthesitis at Baseline by Leeds Enthesitis Index (LEI). An overall score of 0 to 6 is derived from the presence or absence of tenderness at 6 enthesial 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.

Number participants meeting achievement of MDA where an MDA response is achievement of 5 of 7 following outcomes at Week 16:

1. Tender joint count ≤ 1
2. Swollen joint count ≤ 1
3. Psoriasis Area and Severity Index (PASI) ≤ 1 or body surface area (BSA) ≤ 3%
4. Patient assessment of psoriatic arthiritis (PsA) pain ≤ 15
5. Patient Global Assessment of PsA disease activity ≤ 20
6. HAQ-DI ≤ 0.5
7. Tender enthesial points ≤ 1

FACIT-Fatigue evaluates 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 or symptoms of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. The recall period is 7 days. Each item is rated on a 5-point Likert scale ranging from 0 = "not at all" to 4 = "very much." Sum scores for the 13 items range from 0 through 52, where higher scores indicate less fatigue. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in FACIT-Fatigue indicates an improvement.

Number of participants meeting dactylitis resolution at Week 16 among the participants with dactylitis at baseline, where resolution is defined as a tender dactylitis count of 0 in participants with a tender dactylitis count ≥ 1 at baseline. The number of digits in hands and feet with dactylitis will be counted by a blinded assessor.

The American College of Rheumatology (ACR) 50 is defined as 50% improvement over baseline in tender (68) and swollen (66) joint counts and a 50% improvement in 3 of the 5 remaining core data set measures: Participant Global Assessment of Disease Activity; Participant Global Assessment of Pain; Participant assessment of physical function; Physician Global Assessment of psoriatic arthritis; and Acute phase reactant value of high sensitivity C-reactive protein (hsCRP). Baseline is defined as the last measurement on or prior to date/time of first dose of study treatment.

The American College of Rheumatology (ACR) 70 is defined as 70% improvement over baseline in tender (68) and swollen (66) joint counts and a 70% improvement in 3 of the 5 remaining core data set measures: Participant Global Assessment of Disease Activity; Participant Global Assessment of Pain; Participant assessment of physical function; Physician Global Assessment of psoriatic arthritis; and Acute phase reactant value of high sensitivity C-reactive protein (hsCRP). Baseline is defined as the last measurement on or prior to date/time of first dose of study treatment.

HAQ-DI is a patient-reported outcome measure that assesses the degree of difficulty a participant 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 items. For each item in the questionnaire, the level of activity is scored from 0 to 3, with 0 representing "no difficulty," 1 representing "some difficulty," 2 representing "much difficulty," and 3 representing "unable to do." increasing scores for the 8 disability categories indicate increasing level of difficulty. HAQDI is calculated by summing the adjusted categories scores and dividing by the number of categories answered. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in HAQ-DI indicates an improvement.

Number of participants who achieve a clinically meaningful improvement (≥ 0.35 improvement from baseline) in HAQ-DI score among participants with a HAQ-DI score ≥ 0.35 at baseline. HAQ-DI is a patient-reported outcome measure that assesses the degree of difficulty a participant 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 items. For each item in the questionnaire, the level of activity is scored from 0 to 3, with 0 representing "no difficulty," 1 representing "some difficulty," 2 representing "much difficulty," and 3 representing "unable to do." increasing scores for the 8 disability categories indicate increasing level of difficulty. HAQDI is calculated by summing the adjusted categories scores and dividing by the number of categories answered.

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. PASI 75 is the number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value. Baseline is defined as the last measurement on or prior to date/time of first dose of study treatment.

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. PASI 90 is the number of participants who experience at least a 90% improvement in PASI score as compared with the baseline value. Baseline is defined as the last measurement on or prior to date/time of first dose of study treatment.

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. PASI 100 is the number of participants who experience at least a 100% improvement in PASI score as compared with the baseline value. Baseline is defined as the last measurement on or prior to date/time of first dose of study treatment.

SF-36 is a generic 36-item questionnaire measuring health-related quality of life. The physical component summary (PCS) consists of these 4 subscales: Physical functioning, Role-physical, Bodily pain, General health. The scores range from 0 to 100, with a higher score indicating better quality of life. The PCS summary scores will be calculated by taking a weighted linear combination of the individual subscales. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in SF-36 PCS indicates an improvement.

Number of participants meeting enthesitis resolution (score of 0) among participants with enthesitis at Baseline by Leeds Enthesitis Index (LEI). An overall score of 0 to 6 is derived from the presence or absence of tenderness at 6 enthesial 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.

Number of participants meeting enthesitis resolution (score of 0) among participants with enthesitis at Baseline by SPARCC. The SPARCC Enthesitis Index has a 0 to 16 score that is derived from the evaluation of 8 locations: the greater trochanter (right [R]/left [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 supraspinatus insertion (R/L). A higher count indicates a higher enthesitis burden based on the current evaluation.

Number participants meeting achievement of MDA where an MDA response is achievement of 5 of 7 following outcomes at Week 16:

1. Tender joint count ≤ 1
2. Swollen joint count ≤ 1
3. Psoriasis Area and Severity Index (PASI) ≤ 1 or body surface area (BSA) ≤ 3%
4. Patient assessment of psoriatic arthiritis (PsA) pain ≤ 15
5. Patient Global Assessment of PsA disease activity ≤ 20
6. HAQ-DI ≤ 0.5
7. Tender enthesial points ≤ 1

SF-36 is a generic 36-item questionnaire measuring health-related quality of life. The mental component summary (MCS) of the SF-36 consists of these 4 subscales: Vitality, Social functioning, Role-emotional, Mental health. The scores range from 0 to 100, with a higher score indicating better quality of life. The MCS summary scores will be calculated by taking a weighted linear combination of the individual subscales. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in SF-36 MCS indicates an improvement.

FACIT-Fatigue evaluates 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 or symptoms of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. The recall period is 7 days. Each item is rated on a 5-point Likert scale ranging from 0 = "not at all" to 4 = "very much." Sum scores for the 13 items range from 0 through 52, where higher scores indicate less fatigue. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in FACIT-Fatigue indicates an improvement.

Number of participants meeting dactylitis resolution at Week 16 among the participants with dactylitis at baseline, where resolution is defined as a tender dactylitis count of 0 in participants with a tender dactylitis count ≥ 1 at baseline. The number of digits in hands and feet with dactylitis will be counted by a blinded assessor.

The Psoriatic Arthritis Impact of Disease (PsAID) is a 12-item self-report that measures PsA symptoms and impact of disease. Each item is scored on a 0 to 10 numeric rating scale with a 1-week recall period. The PsAID has a total score, with a higher value indicating worse health. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in PsAID indicates an improvement.

The Disease Activity Index for Psoriatic Arthritis Score is a composite measure to assess peripheral joint involvement that is based upon numerical summation of 5 variables of disease activity: tender joint count (0-68), swollen joint count (0-66), Participant Global Assessment of Disease Activity (0 to 10 cm VAS, 0= excellent and 10= poor), Participant Global Assessment of Pain (0 to 10 centimeter [cm] visual analog scale (VAS), 0= no pain, 10= worst possible pain), and C-reactive protein. A higher DAPSA score indicated more active disease activity. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in DAPSA indicates an improvement.

The Disease Activity Index for Psoriatic Arthritis Score is a composite measure to assess peripheral joint involvement that is based upon numerical summation of 5 variables of disease activity: tender joint count (0-68), swollen joint count (0-66), Participant Global Assessment of Disease Activity (0 to 10 cm VAS, 0= excellent and 10= poor), Participant Global Assessment of Pain (0 to 10 centimeter [cm] visual analog scale (VAS), 0= no pain, 10= worst possible pain), and C-reactive protein. A higher DAPSA score indicated more active disease activity.

The Disease Activity Index for Psoriatic Arthritis Score is a composite measure to assess peripheral joint involvement that is based upon numerical summation of 5 variables of disease activity: tender joint count (0-68), swollen joint count (0-66), Participant Global Assessment of Disease Activity (0 to 10 cm VAS, 0= excellent and 10= poor), Participant Global Assessment of Pain (0 to 10 centimeter [cm] visual analog scale (VAS), 0= no pain, 10= worst possible pain), and C-reactive protein. A higher DAPSA score indicated more active disease activity.

The overall condition of the fingernails is rated on a 5-point scale: 0 = clear, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe.

The DAS28-CRP is a composite outcome measure that assesses: 1) How many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints but excluding DIPs), wrists, elbows, shoulders, and knees are swollen and/or tender out of a total of 28; 2) CRP in the blood to measure the degree of inflammation; 3) Participant Global Assessment of Disease Activity. DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. The results are combined to produce the DAS28-CRP score, which correlates with the extent of disease activity: < 2.6: Disease remission, 2.6 to 3.2: Low disease activity, 3.2 to 5.1: Moderate disease activity, > 5.1: High disease activity. Change from baseline is defined as value at post-baseline visit. A negative change from baseline in DAS28-CRP indicates an improvement.

The DAS28-CRP is a composite outcome measure that assesses: 1) How many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints but excluding DIPs), wrists, elbows, shoulders, and knees are swollen and/or tender out of a total of 28; 2) CRP in the blood to measure the degree of inflammation; 3) Participant Global Assessment of Disease Activity. DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. The results are combined to produce the DAS28-CRP score, which correlates with the extent of disease activity: < 2.6: Disease remission, 2.6 to 3.2: Low disease activity, 3.2 to 5.1: Moderate disease activity, > 5.1: High disease activity.

The DAS28-CRP is a composite outcome measure that assesses: 1) How many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints but excluding DIPs), wrists, elbows, shoulders, and knees are swollen and/or tender out of a total of 28; 2) CRP in the blood to measure the degree of inflammation; 3) Participant Global Assessment of Disease Activity. DAS28-CRP scores range from 1.0 to 9.4, where lower scores indicate less disease activity. The results are combined to produce the DAS28-CRP score, which correlates with the extent of disease activity: < 2.6: Disease remission, 2.6 to 3.2: Low disease activity, 3.2 to 5.1: Moderate disease activity, > 5.1: High disease activity.

The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite measure calculated from the Physician Global Assessment of PsA, the Participant Global Assessment of Disease Activity, the Short Form-36 PCS, the swollen joint count, the tender joint count, the Enthesitis (LEI), the Dactylitis (LDI) (Basic), and the High-sensitivity C-reactive protein (hsCRP). The range of PASDAS is 0-10. Higher score means more active disease. Change from baseline is defined as value at post-baseline visit. A negative change from baseline indicates an improvement.

Four domains are used to calculate the modified Composite Psoriatic Disease Activity Index (mCPDAI): joints (66 swollen joint count and 68 tender joint count; Health Assessment Questionnaire), skin (PASI and DLQI), dactylitis (a simple count of each digit involved), and enthesitis (number of tendons/fascia insertion sites showing enthesitis scored from 0 to 4, based on palpation of Achilles tendon and bilateral plantar fasciae insertion). The mCPDAI is scored using a 4 point scale from 0 (no disease activity) to 3 (most severe disease activity), giving an mCPDAI score range of 0 through 12. A higher score indicates more active disease activity. Change from baseline is defined as value at post-baseline visit. A negative change from baseline indicates an improvement.

The Psoriatic Arthritis Response Criteria (PsARC) consists of 4 measurements: tender joint count, swollen joint count, Physician Global Assessment of PsA, and Participant Global Assessment of Disease Activity. In order to be classified as a PsARC responder, participants must achieve improvement in 2 of 4 measures, 1 of which must be joint pain or swelling, without worsening in any measure. Improvement in each of the measures is defined below: 1) Decrease of ≥ 30% in tender joint counts; 2) Decrease of ≥ 30% in swollen joint counts; 3) Decrease of ≥ 20% in Physician Global Assessment of PsA; 4) Decrease of ≥ 20% in Participant's Global Assessment of Disease Activity

BASDAI consists of a 0 to 10 scale measuring discomfort, pain, and fatigue in response to 6 questions pertaining to the 5 major symptoms of ankylosing spondylitis: 1) Fatigue (medical); 2) Spinal pain; 3) Joint pain and swelling; 4) Areas of localized tenderness; 5) Morning stiffness duration; 6) Morning stiffness severity. A higher count indicates worse disease. Each individual question response is scaled to a 0-10 score by dividing by 10, and the BASDAI is derived using the following formula: BASDAI = ((Q1 + Q2 + Q3 + Q4) + ((Q5 + Q6) / 2)) / 5

The WPAI is a 6-item questionnaire that includes 2 visual analog scales: 1 for impact of disease on work and 1 for impact of disease on other daily activities. The WPAI also assesses absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity (overall work impairment/absenteeism plus presenteeism), and activity impairment. These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity. Change from baseline is defined as value at post-baseline visit. A negative change from baseline indicates an improvement.

The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. Change from Baseline in 5-level EuroQol 5-dimension (EQ-5D-5L) Utility Scores. Change from baseline is defined as value at post-baseline visit. A negative change from baseline indicates an improvement.

The Patient-Reported Outcome Measures Information System Sleep Disturbance Short Form 8b assess self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. This includes perceived difficulties and concerns with getting to sleep or staying asleep, as well as perceptions of the adequacy of and satisfaction with sleep. The items are evaluated on a 5-point Likert scale ranging from 1 = "not at all" to 5 = "very much" with a 7-day recall period. Higher score means more active disease. Change from baseline is defined as value at post-baseline visit. A negative change from baseline indicates an improvement.