# Improvements in Patient-Reported Outcomes After Treatment With Deucravacitinib in Patients With Psoriatic Arthritis: Results From a Randomized Phase 2 Trial

Vibeke Strand, Laure Gossec, Laura Coates, Alexis Ogdie, Jiyoon Choi, Brandon Becker, Joe Zhuo, Thomas Lehman, Miroslawa Nowak, Ayanbola Elegbe, et al.

► To cite this version:

Vibeke Strand, Laure Gossec, Laura Coates, Alexis Ogdie, Jiyoon Choi, et al. Improvements in Patient-Reported Outcomes After Treatment With Deucravacitinib in Patients With Psoriatic Arthritis: Results From a Randomized Phase 2 Trial. Arthritis Care & Research = Arthritis Care and Research, 2024, 76 (8), pp.1139-1148. 10.1002/acr.25333. hal-05000511

HAL Id: hal-05000511

https://hal.science/hal-05000511v1

Submitted on 21 Mar 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# Improvements in Patient-Reported Outcomes After Treatment With Deucravacitinib in Patients With Psoriatic Arthritis: Results From a Randomized Phase 2 Trial

Vibeke Strand, MD¹; Laure Gossec, MD, PhD²,³; Laura C. Coates, MBChB, PhD⁴; Alexis Ogdie, MD, MSCE⁵; Jiyoon Choi, PharmD, MBA⁶; Brandon Becker, PhD⁶; Joe Zhuo, PhD⁶; Thomas Lehman, PharmD⁶; Miroslawa Nowak, MD⁶; Ayanbola Elegbe, PhD⁶; Philip J. Mease, MD⁷; Atul Deodhar, MD⁸

¹Division of Immunology/Rheumatology, Stanford University, Palo Alto, CA, USA; ²Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France;

³Rheumatology Department, AP-HP, Pitié-Salpêtrière Hospital, Paris, France⁴; Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK;

⁵Division of Rheumatology and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; ⁶Bristol Myers Squibb, Princeton, NJ, USA; ⁷Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, WA, USA; ⁸Oregon Health & Science University, Portland, OR, USA

## Corresponding author:

Vibeke Strand, MD
Adjunct Clinical Professor
Division of Immunology and Rheumatology
Stanford University School of Medicine
291 Campus Drive
Li Ka Shing Building
Palo Alto, CA 94305
Tel: 650-400-2073
Email: vibekestrand@me.com
ORCID: 0000-0003-4978-4072

**Running head:** Deucravacitinib in patients with psoriatic arthritis

## FUNDING

This study was sponsored by Bristol Myers Squibb.

## CONFLICTS OF INTEREST/DISCLOSURES

VS has served as a consultant for AbbVie, Amgen, Arena, AstraZeneca, Bayer, Biosplice, Bioventus, Blackrock, BMS, Boehringer Ingelheim, Celltrion, ChemoCentryx, EMD Serono, Equilibrium, Eupraxia, Flexion, Galapagos, Genentech/Roche, Gilead, GSK, Horizon, Ichnos, Inmedix, Janssen, Kiniksa, Kypha, Lilly, Merck, MiMedx, Novartis, Pfizer, Regeneron, Rheos, Samsung, Sandoz, Sanofi, Scipher, Servier, Setpoint, Spherix, Sun Pharma, Tonix, and UCB. LG has received grants or contracts from Sandoz and UCB; consulting fees from AbbVie, Bristol Myers Squibb, Celltrion, Galapagos, Janssen, Novartis, Pfizer, and UCB; honoraria for lectures from AbbVie, Amgen, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz, and UCB; support for attending meetings and/or travel from MSD, Novartis, and Viatris; and medical writing support from AbbVie, Janssen, Pfizer, and UCB. LCC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, and Novartis; served as a paid consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB; and served as a paid speaker for AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer, and UCB. AO has
served on consulting/advisory boards for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Corrona, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB; has received grants from Pfizer to Penn, Novartis to Penn, and Amgen to Forward/NDB; and received royalties from Novartis to husband. PJM has received research grants from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sun Pharma, and UCB; and has received consulting and/or speaker fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB. AD has served on consulting and/or advisory boards for AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, and UCB; and has received research grants from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galvani, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, and UCB. JZ, MN, BB, TL, and AE are employees of and shareholders in Bristol Myers Squibb. JC is an employee of Bristol Myers Squibb and a shareholder in Johnson & Johnson.

## ABSTRACT

**Objective:** Deucravacitinib, a tyrosine kinase 2 inhibitor, was assessed in a phase 2 trial in patients with active psoriatic arthritis (PsA). Here, we report effects of deucravacitinib from the patient perspective.

**Methods:** This phase 2, double-blind trial (NCT03881059) randomized patients with active PsA 1:1:1 to deucravacitinib 6 mg once daily (QD), 12 mg QD, or placebo, for 16 weeks. Key secondary end points were changes from baseline (CFBs) at week 16 in Health Assessment Questionnaire-Disability Index (HAQ-DI) and 36-item Short-Form Health Survey (SF-36) physical component summary (PCS) scores. Additional patient-reported outcomes (PROs) assessed disease impact, including fatigue, pain, and mental health. The mean CFBs in PROs and percentages of patients reporting improvements with minimum clinically important differences (MCIDs) or scores of greater than normal values were also assessed.

**Results:** This study comprised 203 patients (51.2% female; mean ± SD age, 49.8 ± 13.5 years). At week 16, the adjusted mean difference (95% confidence interval) versus placebo in HAQ-DI and SF-36 PCS CFB was significant for each deucravacitinib group (HAQ-DI 6 mg, -0.26 [-0.42 to -0.10], P = 0.0020; HAQ-DI 12 mg, -0.28 [-0.45 to -0.12], P = 0.0008; SF-36 PCS 6 mg, 3.3 [0.9 to 5.7], P = 0.0062; SF-36 PCS 12 mg, 3.5 [1.1 to 5.9], P = 0.0042). MCID at week 16 were reported for all PROs with either dose of deucravacitinib. Improvements of MCID or to normative values were reported by more patients receiving deucravacitinib than placebo.

**Conclusion:** Deucravacitinib groups demonstrate significant and clinically meaningful improvements in PROs versus placebo in patients with active PsA, which warrants further study.

**Keywords:** Health-related quality of life; HRQoL; patient-reported outcome; psoriatic arthritis; psoriasis; tyrosine kinase 2; TYK2
SIGNIFICANCE AND INNOVATIONS

* Patient-reported outcomes representing a broad range of disease impacts are both important to patients with psoriatic arthritis (PsA) and critical to support physician-derived clinical efficacy data

* Patients with PsA who received deucravacitinib 6 mg or 12 mg once daily (QD) experienced significant improvements in the key secondary endpoints in this phase 2 double-blind trial, including change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) and 36-item Short-Form Health Survey physical component summary scores at Week 16

* Clinically meaningful improvements from baseline in HAQ-DI, Patient Global Assessment of Disease Activity, and Functional Assessment of Chronic Illness Therapy-Fatigue and -Pain were reported by patients who received either dose of deucravacitinib
Introduction

The disease burden of psoriatic arthritis (PsA) is substantial, with considerable impairment in patients' physical and emotional functioning, and health-related quality of life (HRQoL).1 In patients with PsA, pain, fatigue, and declines in physical functioning, ability to perform activities of daily living, and overall mental health are frequent.2 Real-world data demonstrate that fatigue is prevalent in patients with PsA (78%) and is associated with substantially decreased HRQoL.3 In one large-scale, cross-sectional survey (N = 3,200) assessing the disease burden in patients with PsA, 41% reported having anxiety and/or depression, and the majority (65%) indicated that their PsA symptoms contributed to their anxiety and/or depression.4 Finally, patients with PsA often have multiple comorbidities, requiring multiple treatments and, consequently, careful navigation of potential adverse drug-drug interactions.5

Current therapeutic options for PsA include conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs, such as apremilast and JAK 1/2/3 inhibitors.6 Although patients respond to these therapies, efficacy diminishes over time, resulting in the inadequate treatment of a chronic, lifelong disease.7 Accordingly, more than 80% of participants in a real-world study discontinued their index treatment over a 2-year follow-up period.8 Suboptimal therapy can lead to treatment switching, which is associated with increased treatment costs.9 Thus, an unmet need exists for safe and efficacious therapies, with novel mechanisms of action (MoAs) that treat the clinical manifestations of disease and improve HRQoL in patients with active PsA.

Tyrosine kinase 2 (TYK2) is an intracellular enzyme that mediates signaling of key cytokines (eg, interleukin-23, interleukin-12, and Type I interferons) involved in the pathogenesis of PsA, plaque psoriasis, and other immune-mediated diseases.10 Additionally, genes representing TYK2 and TYK2 pathway cytokines include several differentially regulated genes expressed in patients with PsA.1 Deucravacitinib is a first-in-class, oral, selective, allosteric TYK2 inhibitor approved in multiple countries for the treatment of adults with moderate-to-severe plaque psoriasis.11-14 Deucravacitinib has an MoA distinct from that of JAK 1/2/3 inhibitors; it binds to the regulatory domain of TYK2 rather than to the more conserved catalytic domain where current JAK 1/2/3 inhibitors bind.10 Binding to the TYK2 regulatory domain locks the enzyme in an inactive state, resulting in selective inhibition of immune-related pathways. Unlike the JAK 1/2/3 inhibitors, deucravacitinib does not inhibit metabolic or hematopoietic pathways.15 This high selectivity for TYK2 results in minimal activity against JAK 1/2/3 and offers a different and more favorable risk profile compared with current JAK 1/2/3 inhibitors.16

In psoriasis, deucravacitinib has shown superior efficacy to apremilast, a phosphodiesterase 4 inhibitor, in the phase 3 POETYK PSO-1 and POETYK PSO-2 head-to-head trials. Deucravacitinib was well tolerated and significantly more efficacious than placebo in one phase 2 and three phase 3 trials in patients with moderate-to-severe plaque psoriasis (POETYK PSO-1, POETYK PSO-2, and POETYK PSO-3),17-21 as well as in one phase 2 trial of patients with systemic lupus erythematosus (PAISLEY).22 Further, deucravacitinib was well tolerated and more efficacious than placebo in a phase 2 trial of patients with active PsA,23 where the primary end point of significant improvements, according to American College of Rheumatology 20% improvement criteria (ACR20) response rates, occurred with both 6 mg once daily (QD) (P ≤ 0.05) and 12 mg QD (P ≤ 0.001) versus placebo at week 16.23, 24

Patient-reported outcomes (PROs) directly measure how a patient feels and functions and are considered highly relevant and important end points in clinical trials.25-27 Indeed, the PsA core
domain set endorsed by Outcome Measures in Rheumatology (OMERACT) identifies fatigue, pain, patient global assessment of disease activity, physical function, and HRQoL as critical measures to be assessed in clinical trials.²⁸ Given the deleterious effect of PsA on HRQoL, it is important to assess PROs when evaluating treatment benefits. Here, we present a detailed characterization of the effect of deucravacitinib on PROs in patients with PsA.

# PATIENTS AND METHODS

## Study design and patient population

This phase 2, placebo-controlled, double-blind, randomized trial (NCT03881059) was described previously.²³ Patients with a PsA diagnosis for ≥6 months who fulfilled the Classification Criteria for Psoriatic Arthritis at screening with active joint disease (defined as ≥3 tender and ≥3 swollen joints), 3 mg/L or higher high-sensitivity C-reactive protein, and ≥1 plaque psoriasis lesion (of ≥2 cm) were enrolled. Eligible patients must have failed or have been intolerant to ≥1 nonsteroidal anti-inflammatory drug or conventional DMARD and/or one tumor necrosis factor inhibitor (TNFi). Patients with nonplaque psoriasis morphologies, other autoimmune conditions, or active fibromyalgia were excluded. Patients were randomized 1:1:1 to receive deucravacitinib 6 mg or 12 mg QD, or a placebo for 16 weeks. This trial was conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Guidelines for Good Clinical Practice, and local regulations. An institutional review board or independent ethics committee at each site approved the protocol, consent form, and any other written information provided to patients. All patients provided written informed consent before study participation.

## PROs

PROs were assessed using the PsA-specific 12-item Psoriatic Impact of Disease (PsAID-12)²⁹ as well as the generic PRO instruments Health Assessment Questionnaire-Disability Index (HAQ-DI),³⁰, ³¹ 13-item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue),³², ³³ Patient Global Assessment of Disease Activity (PtGA) and Patient Global Assessment of Pain (PAIN),³⁴ and 36-Item Short-Form Health Survey (SF-36).³⁴⁻³⁶ Using these instruments, changes from baseline (CFBs) were assessed at week 16. The percentage of patients reporting improvements with at least minimum clinically important differences (MCIDs) and the percentages with scores greater than or equal to age- and sex-matched normative values were determined for each PRO (except for PsAID-12). CFBs in PsAID-12 scores at week 16 were determined by response outcomes (eg, achievement of response at week 16 for PROs and select clinical responses).

The HAQ-DI (MCID, ≥0.35 unit decrease from baseline; normative value, ≤0.25 units) assesses the degree of difficulty a patient experienced during the previous week. Higher scores in the HAQ-DI indicate worse outcomes.³⁰, ³¹ The FACIT-Fatigue instrument (MCID, ≥4-point increase; normative value, ≥40.1 points) evaluates fatigue symptoms experienced over the previous week.³², ³³ PtGA and PAIN, which are both scored using a 0 to 100 visual analog scale (VAS), have defined MCIDs as 10-point decreases that focus on disease activity from the patient perspective, as well as pain intensity.³⁴, ³⁷ The SF-36 version 2 is based on 36 questions and 8 domains (bodily pain, general health, mental health, physical functioning, role—emotional, role—physical, social functioning, and vitality) assessed over the previous week and are summed into the physical component summary (PCS) and mental component summary (MCS) scores (MCID, ≥2.5-point increase; normative value, ≥50 points; SF-36 individual domain scores MCID, ≥5-point increase).³⁴, ³⁶, ³⁸ Scores for each domain range from 0 to 100, with higher scores indicating an improved HRQoL.³⁸ The PsAID questionnaire is a validated
instrument designed to specifically assess the impact of PsA on HRQoL from the patient's perspective and is available as separate versions for clinical practice (PsAID-12).29 Each item in the PsAID is scored on a numeric rating scale ranging from 0 to 10 based on a 1-week recall period. A higher total PsAID score indicates a worse HRQoL.29 A decrease of ≥3 points has been recommended as an MCID.29

In patients with PsA with axial involvement (axPsA) in the opinion of investigators at baseline, symptoms of disease activity were evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; MCID, ≥1.1-point decrease),39 which consists of six questions related to the five major symptoms of ankylosing spondylitis (fatigue, spinal pain, joint pain and swelling, areas of localized tenderness, and morning stiffness duration and severity), rated on a scale ranging from 0 to 100 with a 1-week recall period. A higher score indicates worse disease.39

## Statistical analyses

PRO analyses were performed using the full analysis set, which included all randomized patients assigned to the study drug. As previously described,23 the study sample size was calculated to be sufficient to detect a treatment difference for the primary end point, ACR20 at week 16. CFBs in HAQ-DI and SF-36 PCS scores were key secondary end points and adjusted for multiplicity. Testing of the key secondary end points was conducted sequentially and only proceeded to the next key secondary end point if the null hypothesis was rejected (α = 0.10 [two-sided]) for the prior end point, demonstrating a positive dose response for that end point. If an end point failed at any step, all subsequent P values were considered nominal. All other PRO end points were exploratory and not controlled for multiplicity. Within-group adjusted least-squares mean CFBs and 95% confidence intervals (95% CIs) at week 16 were determined using an analysis of covariance model, with dose level included as a continuous variable and body weight (<90 kg and ≥90 kg) and TNFi use (experienced and naive) per randomization included as fixed effects. The baseline value was included as a covariate in the model.

Spydergrams were used to illustrate CFBs in SF-36 domain and PsAID-12 item scores in each treatment group against a combined baseline US age- and sex-matched normative population.40 The number needed to treat (NNT) reflects the number of people who need to receive treatment for a single patient to benefit.41 NNT was calculated as 1/(deucravacitinib response–placebo response). A modified baseline observation carried forward method was used for continuous end points when patients discontinued study treatment because of lack of efficacy or adverse events or for starting a protocol-prohibited treatment.23 Patients who discontinued study treatment for other reasons had missing data imputed using the last observation carried forward method. Spearman correlations were calculated to evaluate the relationships between PsAID-12 scores, PROs, and select clinical outcomes at baseline and at week 16. These post hoc analyses did not control for multiple comparisons.

# RESULTS

## Patients

In total, 203 patients with PsA were included in this analysis. Of those, 50 (24.6%) had axPsA in the opinion of investigators but not confirmed by imaging. Demographic and baseline clinical characteristics were generally balanced across treatment groups (Table 1).

## Patient-reported outcomes: change from baseline at week 16

Patients who took deucravacitinib 6 mg QD and 12 mg QD demonstrated significant improvements from baseline versus placebo in HAQ-DI (adjusted P ≤ 0.002) and SF-36 PCS
(adjusted $P \le 0.006$) scores compared with patients taking placebo at week 16. The adjusted mean difference (95% CI) versus the placebo group for CFB in HAQ-DIs at week 16 was -0.26 (-0.42 to -0.10) and -0.28 (-0.45 to -0.12) for the deucravacitinib 6 mg QD and 12 mg QD groups, respectively. The adjusted mean difference (95% CI) versus the placebo group for CFBs in SF-36 PCSs at week 16 was 3.3 (0.9-5.7) and 3.5 (1.1-5.9) for the deucravacitinib 6 mg QD and 12 mg QD groups, respectively. The MCS scores and PsAID-12 were improved compared with the placebo group at week 16. FACIT-Fatigue scores improved from baseline to week 16 by mean (95% CI) 5.6 (3.4-7.9) and 7.2 (4.9-9.5) for the deucravacitinib 6 mg QD and 12 mg QD groups, respectively, compared with 2.8 (0.5-5.1) for the placebo group (Table 2).

Improvements from baseline in PtGA and PAIN were numerically greater with both doses of deucravacitinib compared with the placebo group. Adjusted mean CFBs in SF-36 scores were better in five of eight domains with the deucravacitinib 6 mg QD group (physical functioning, role-physical, bodily pain, vitality, and social functioning) and in six of eight domains with the deucravacitinib 12 mg QD group (role-emotional in addition to the 6 mg group domains) compared with the placebo group (Figure 1A). Similarly, adjusted mean CFBs in PsAID-12 item scores were improved in 10 of 12 items with the deucravacitinib 6 mg QD group (pain; work or leisure; functional capacity; discomfort; sleep disturbance; coping; anxiety, fear, or uncertainty; embarrassment or shame, social participation; and depression) and in all 12 items in the deucravacitinib 12 mg QD group (fatigue and skin problems in addition to the other 10 items) (Figure 1B).

## Patient-reported outcomes: clinically meaningful improvements from baseline at Week 16

Greater percentages of patients reported improvements in all PROs in the deucravacitinib groups compared with the placebo group. Greater percentages of patients reported improvements in HAQ-DI and PtGA at week 16 with both doses of deucravacitinib versus placebo and in FACIT-Fatigue and PAIN scores in those receiving deucravacitinib 12 mg QD versus placebo (Figure 2). Greater percentages of patients reported improvements greater than or equal to MCID in two SF-36 domains (physical functioning and social functioning) in the group receiving deucravacitinib 12 mg QD and in three domains (role-physical in addition to the other two domains) in the group receiving deucravacitinib 6 mg QD versus those receiving placebo. Greater percentages of patients receiving deucravacitinib 12 mg QD reported improvements greater than or equal to MCIDs in BASDAI at week 16 versus those receiving placebo. Greater percentages of patients reported improvements greater than or equal to MCID in PsAID-12 scores at week 16 with both doses of deucravacitinib versus placebo. Improvements in PROs that were greater than or equal to MCIDs with deucravacitinib treatment generally resulted in clinically meaningfully low patient NNTs (≤10).

Each treatment group demonstrated an increase from baseline in the percentages of patients reporting PRO scores greater than or equal to normative values at week 16, with the exception of SF-36 MCS and social functioning, role-emotional, and mental health domains in the placebo group, which decreased at week 16 (Figure 3). The percentages of patients reporting scores greater than or equal to normative values were numerically greater with both deucravacitinib doses compared with placebo across all PROs evaluated at week 16.

The proportions of patients reporting ≥50% improvement from baseline in BASDAI in patients with baseline clinical diagnosis of axPsA were greater in the deucravacitinib 6 mg QD (26.3%) and deucravacitinib 12 mg QD groups (25.0%) than in the placebo group (13.3%) at week 16. Similarly, the proportions of patients with active disease (baseline BASDAI ≥4)39 with a ≥50% improvement from baseline were also greater in the deucravacitinib groups (6 mg QD, 25.0%; 12 mg QD, 20.0%; placebo, 7.1%).
**Relationship between PsAID-12 scores and other patient-reported outcomes and select clinical outcomes**

Patients with clinically meaningful responses in most other PROs and select clinical outcomes, including Psoriatic Arthritis Disease Activity scores, low disease activity, and 75% improvement from baseline in the Psoriasis Area and Severity Index, also reported improvements from baseline in PsAID-12 scores in both deucravacitinib dose groups versus the placebo group at week 16 (Figure 4). Some patients without responses in other outcomes still experienced improvements from baseline in total PsAID-12 scores. Spearman correlation analysis revealed correlations at baseline and week 16 between PsAID-12 scores and PROs and clinical outcomes, including the Physician Global VAS (Supplementary Table 1).
DISCUSSION

The present analysis representing a broad range of PROs important to patients demonstrated that deucravacitinib improved physical and social functioning, mental health, fatigue, and pain in a phase 2 trial in patients with active PsA. These findings were supported by both PsA-specific (PsAID-12) and nonspecific (PtGA, PAIN, HAQ-DI, and SF-36 PCS and MCS and FACIT-Fatigue) PRO instruments.

Statistically significant and clinically meaningful improvements from baseline to week 16 for the key secondary end points (HAQ-DI and SF-36 PCS) were reported by patients treated with deucravacitinib 6 mg QD or 12 mg QD versus placebo. Furthermore, clinically meaningful improvements from baseline to week 16 were also evident in SF-36 MCS and PsAID-12 scores for patients receiving deucravacitinib 6 mg QD or 12 mg QD compared with the placebo group. Improvements were evident in patients treated with deucravacitinib based on total SF-36 and PsAID-12 scores, as well as specific SF-36 domain and PsAID-12 item scores. Numeric improvements in FACIT-Fatigue, PtGA, and PAIN scores were reported with both deucravacitinib doses versus placebo. A higher proportion of patients receiving deucravacitinib compared with placebo reported improvements from baseline that were greater than or equal to MCIDs, and PRO scores that were greater than or equal to normative values, which is indicative of improving HRQoL in the patient population included in this analysis. Both doses of deucravacitinib resulted in NNTs of ≤10, which is considered clinically meaningful.41 NNTs were comparable for the deucravacitinib 6 mg QD and 12 mg QD groups measured by PtGA, HAQ-DI, and SF-36 PCS and MCS scores. The PsA-specific PRO, PsAID-12, detected additional improvements in HRQoL (approximately three points, the MCID) in patients treated with deucravacitinib with responses in multiple other PROs and selected clinical outcomes, indicating a clear improvement in the PsA-related impact on HRQoL.

The results of this analysis are consistent with those of the primary and secondary clinical outcomes in the phase 2 trial, thereby demonstrating that deucravacitinib provides both clinical and patient-reported benefits in people with active PsA.23 Deucravacitinib treatment also provided benefit to patients with plaque psoriasis. In the phase 3 POETYK PSO-1, POETYK PSO-2, and POETYK PSO-3 trials, deucravacitinib was associated with greater improvements in the Dermatology Life Quality Index and Psoriasis Symptoms and Signs Diary (PSSD) scores compared with placebo during 16 weeks of double-blind treatment.18-20 Additionally, deucravacitinib was superior to apremilast in its impact on PSSD scores in the POETYK PSO-1 and POETYK PSO-2 trials by week 16.18, 19 Improvements in PROs in patients with plaque psoriasis are noteworthy given that the majority of patients (78% to 84%) in this phase 2 PsA trial had comorbid psoriasis. Collectively, these results support the use of deucravacitinib to achieve clinical and patient-reported HRQoL improvements in PsA symptoms.

Some limitations should be considered when interpreting the results of this trial. Only two key secondary end points (HAQ-DI and SF-36 PCS) were controlled for multiplicity, and the remaining post hoc analyses did not adjust for multiple comparisons. Sample size and study power were calculated based on the primary end point (ACR20 response at week 16) only.23 The sample size (203 patients) was relatively small, and the trial duration (16 weeks) was short, which may limit the generalizability of these findings to a broader patient population. However, it should be noted that the number of patients is consistent with expectations for a phase 2 trial, and the patient population was similar, in terms of HRQoL and other PROs at baseline, to populations in other PsA trials.29, 42, 43 The effect of deucravacitinib treatment on PROs will
be further evaluated in ongoing phase 3 trials in active PsA (NCT04908202 and NCT04908189). Finally, the classification of axPsA was based on the opinion of the investigators, and the BASDAI relies on patients' perception of their disease. Moreover, improvements in peripheral arthritis and enthesitis may lower an overall BASDAI score without improving spinal inflammation.44 Additional research is necessary to understand the efficacy of deucravacitinib in patients with axPsA.

Previous studies have established that PsA negatively affects various aspects of patients' lives, including the ability to perform daily activities, participation in social activities, and psychological well-being.45-49 The assessments used in this study evaluated impacts of PsA that are important to patients and align with the PsA core domains endorsed by OMERACT, highlighting the validity of these findings.28 Deucravacitinib is a promising therapeutic option for improving HRQoL and other PROs in patients with PsA.

## ACKNOWLEDGMENTS

The authors acknowledge the contributions of June Ye, PhD, and Lan Wei to the analysis of clinical data. Medical writing and editorial assistance was provided by Ann Marie Fitzmaurice, PhD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Bristol Myers Squibb.

## AUTHOR CONTRIBUTIONS

**Study conception and design:** Vibeke Strand, Laure Gossec, Jiyoon Choi, Brandon Becker, Tom Lehman, Miroslawa Nokak, Philip P Mease, Atul Deodhar.

**Acquisition of data:** Jiyoon Choi and Brandon Becker.

**Analysis and interpretation of data:** All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Vibeke Strand had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

## ROLE OF THE STUDY SPONSOR

This study and manuscript were funded by Bristol Myers Squibb. Bristol Myers Squibb employees were involved in the study design, the collection, analysis, and interpretation of data, the review of the manuscript, and the decision to submit the manuscript. Publication of this article was not contingent upon approval by Bristol Myers Squibb.

## REFERENCES

1. Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med 2017;376:957-70.

2. Kavanaugh A, Helliwell P, Ritchlin CT. Psoriatic arthritis and burden of disease: patient perspectives from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey. Rheumatol Ther 2016;3:91-102.

3. Gossec L, Walsh JA, Michaud K, Holdsworth E, Peterson S, Meakin S, et al. Effect of fatigue on health-related quality of life and work productivity in psoriatic arthritis: findings from a real-world survey. J Rheumatol 2022;49:1221-8.

4. Tillett W, Merola JF, Thaçi D, Holdsworth E, Booth N, Lobosco LS, et al. Disease characteristics and the burden of joint and skin involvement amongst people with psoriatic arthritis: a population survey. Rheumatol Ther 2020;7:617-37.

5. Husted JA, Thavaneswaran A, Chandran V, Gladman DD. Incremental effects of comorbidity on quality of life in patients with psoriatic arthritis. J Rheumatol 2013;40:1349-56.
6. Gossec L, Smolen JS, Ramiro S, de Wit M, Cutolo M, Dougados M, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis 2016;75:499-510.

7. Lebwohl MG, Bachelez H, Barker J, Girolomoni G, Kavanaugh A, Langley RG, et al. Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol 2014;70:871-81.e1-30.

8. Walsh JA, Cai Q, Lin I, Fitzgerald T, Pericone CD, Chakravarty SD. Real-world 2-year treatment patterns among patients with psoriatic arthritis treated with injectable biologic therapies. Curr Med Res Opin 2020;36:1245-52.

9. Wu JJ, Pelletier C, Ung B, Tian M, Khilfeh I, Curtis JR. Treatment switch patterns and healthcare costs in biologic-naïve patients with psoriatic arthritis. Adv Ther 2020;37:2098-115.

10. Palmer JB, Li Y, Herrera V, Liao M, Tran M, Ozturk ZE. Treatment patterns and costs for anti-TNFα biologic therapy in patients with psoriatic arthritis. BMC Musculoskelet Disord 2016;17:261.

11. Burke JR, Cheng L, Gillooly KM, Strnad J, Zupa-Fernandez A, Catlett IM, et al. Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Sci Transl Med 2019;11:eaaw1736.

12. Sotyktu [package insert]. Princeton, NJ, USA: Bristol-Myers Squibb Company; 2022 September 2022.

13. Sotyktu Australian Product Information. Victoria, Australia: Bristol-Myers Squibb Australia Pty Ltd; 2022 December 2022.

14. Sotyktu [product monograph]. Montreal, Canada: Bristol-Myers Squibb Canada Co.; 2022 November 2022.

15. Sotyktu Japan [package insert]. Tokyo, Japan: Bristol-Meyers Squibb K.K.; 2022 26 September 2022.

16. Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol 2017;13:234-43.

17. Krueger JG, McInnes IB, Blauvelt A. Tyrosine kinase 2 and Janus kinase-signal transducer and activator of transcription signaling and inhibition in plaque psoriasis. J Am Acad Dermatol 2022;86:148-57.

18. Strober B, Thaçi D, Sofen H, Kircik L, Gordon KB, Foley P, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 POETYK PSO-2 trial. J Am Acad Dermatol 2023;88:40-51.

19. Armstrong AW, Gooderham M, Warren RB, Papp KA, Strober B, Thaçi D, et al. Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol 2023;88:29-39.

20. Papp K, Gordon K, Thaci D, Morita A, Gooderham M, Foley P, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med 2018;379:1313-21.

21. Zhang J, Ding Y, Hui L, Li L, Pan W, Lu Y, et al., editors. Deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in Asian patients with moderate to severe plaque psoriasis: findings from the phase 3 POETYK PSO 3 trial [oral presentation D3T01.1B]. Annual Congress of the European Academy of Dermatology and Venereology; 2022 7-10 September 2022; Milan, Italy.

22. Imafuku S, Okubo Y, Tada Y, Ohtsuki M, Wang Q, Colston E, et al., editors. Deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in Japanese patients with moderate to severe plaque, erythrodermic, or generalized pustular psoriasis: efficacy
and safety results from the open-label, phase 3 POETYK PSO-4 trial [poster1477]. Annual Congress of the European Academy of Dermatology and Venereology; 2022 7-10 September 2022; Milan, Italy.

23. Morand E, Pike M, Merrill JT, van Vollenhoven R, Werth VP, Hobar C, et al. Deucravacitinib, a tyrosine kinase 2 inhibitor, in systemic lupus erythematosus: a phase II, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol 2023;75:242-52.

24. Mease PJ, Deodhar AA, van der Heijde D, Behrens F, Kivitz AJ, Neal J, et al. Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis 2022;81:815-22.

25. Ogdie A, de Wit M, Callis Duffin K, Campbell W, Chau J, Coates LC, et al. Defining outcome measures for psoriatic arthritis: a report from the GRAPPA-OMERACT working group. J Rheumatol 2017;44:697-700.

26. McGagh D, Coates LC. Assessment of the many faces of PsA: single and composite measures in PsA clinical trials. Rheumatology (Oxford) 2020;59:i29-i36.

27. Jensen RE, Rothrock NE, DeWitt EM, Spiegel B, Tucker CA, Crane HM, et al. The role of technical advances in the adoption and integration of patient-reported outcomes in clinical care. Med Care 2015;53:153-9.

28. Orbai AM, de Wit M, Mease PJ, Callis Duffin K, Elmamoun M, Tillett W, et al. Updating the Psoriatic Arthritis (PsA) Core Domain Set: a report from the PsA Workshop at OMERACT 2016. J Rheumatol 2017;44:1522-8.

29. Mease PJ, Woolley JM, Bitman B, Wang BC, Globe DR, Singh A. Minimally important difference of Health Assessment Questionnaire in psoriatic arthritis: relating thresholds of improvement in functional ability to patient-rated importance and satisfaction. J Rheumatol 2011;38:2461-5.

30. Krishnan E, Sokka T, Hakkinen A, Hubert H, Hannonen P. Normative values for the Health Assessment Questionnaire disability index: benchmarking disability in the general population. Arthritis Rheum 2004;50:953-60.

31. Hewlett S, Dures E, Almeida C. Measures of fatigue: Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF MDQ), Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scales (BRAF NRS) for severity, effect, and coping, Chalder Fatigue Questionnaire (CFQ), Checklist Individual Strength (CIS20R and CIS8R), Fatigue Severity Scale (FSS), Functional Assessment Chronic Illness Therapy (Fatigue) (FACIT-F), Multi-Dimensional Assessment of Fatigue (MAF), Multi-Dimensional Fatigue Inventory (MFI), Pediatric Quality Of Life (PedsQL) Multi-Dimensional Fatigue Scale, Profile of Fatigue (ProF), Short Form 36 Vitality Subscale (SF-36 VT), and Visual Analog Scales (VAS). Arthritis Care Res (Hoboken) 2011;63 Suppl 11:S263-86.

32. Webster K, Cella D, Yost K. The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System: properties, applications, and interpretation. Health Qual Life Outcomes 2003;1:79.

33. Strand V, Boers M, Idzerda L, Kirwan JR, Kvien TK, Tugwell PS, et al. It's good to feel better but it's better to feel good and even better to feel good as soon as possible for as long as possible. Response criteria and the importance of change at OMERACT 10. J Rheumatol 2011;38:1720-7.

34. Ware JE, Jr., Kosinski M, Bjorner JB, Turner-Bowker DM, Gandek B, Maruish ME. User's manual for the SF-36v2 health survey. 2nd ed. Lincoln, RI: QualityMetric Incorporated; 2007.

35. Ware JE, Jr., Kosinski M, Bayliss MS, McHorney CA, Rogers WH, Raczek A. Comparison of methods for the scoring and statistical analysis of SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care 1995;33:AS264-AS79.
36. Gossec L, de Wit M, Kiltz U, Braun J, Kalyoncu U, Scrivo R, et al. A patient-derived and patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country EULAR initiative. Ann Rheum Dis 2014;73:1012-9.

37. Wells GA, Boers M, Shea B, Brooks PM, Simon LS, Strand CV, et al. Minimal disease activity for rheumatoid arthritis: a preliminary definition. J Rheumatol 2005;32:2016-24.

38. Ware JE, Jr., Kosinski M, Bjorner JB, Turner-Bowker DM, Gandek B, Maruish ME. Advantages of Norm-Based Scoring. User's Manual for the SF-36v2 Health Survey. 2nd ed. Lincoln, RI: QualityMetric Incorporated; 2007. p. 81-4.

39. Kviatkovsky MJ, Ramiro S, Landewé R, Dougados M, Tubach F, Bellamy N, et al. The minimum clinically important improvement and patient-acceptable symptom state in the BASDAI and BASFI for patients with ankylosing spondylitis. J Rheumatol 2016;43:1680-6.

40. Strand V, Crawford B, Singh J, Choy E, Smolen JS, Khanna D. Use of "spydergrams" to present and interpret SF-36 health-related quality of life data across rheumatic diseases. Ann Rheum Dis 2009;68:1800-4.

41. Siwek J, Newman DH. Introducing medicine by the numbers: a collaboration of the NNT group and AFP. Am Fam Physician 2015;91:434-5.

42. Lee S, Mendelsohn A, Sarnes E. The burden of psoriatic arthritis: a literature review from a global health systems perspective. P&T 2010;35:680-9.

43. Strand V, Sharp V, Koenig AS, Park G, Shi Y, Wang B, et al. Comparison of health-related quality of life in rheumatoid arthritis, psoriatic arthritis and psoriasis and effects of etanercept treatment. Ann Rheum Dis 2012;71:1143-50.

44. Salaffi F, Carotti M, Gasparini S, Intorcia M, Grassi W. The health-related quality of life in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a comparison with a selected sample of healthy people. Health Qual Life Outcomes 2009;7:25.

45. Kavanaugh A, Marzo-Ortega H, Vender R, Wei CC, Birt J, Adams DH, et al. Ixekizumab improves patient-reported outcomes in patients with active psoriatic arthritis and inadequate response to tumour necrosis factor inhibitors: SPIRIT-P2 results to 52 weeks. Clin Exp Rheumatol 2019;37:566-74.

46. Gudu T, Gossec L. Quality of life in psoriatic arthritis. Expert Rev Clin Immunol 2018;14:405-17.

47. Orbai AM, Ogdie A, Gossec L, Tillett W, Leung YY, Gao J, et al. Effect of filgotinib on health-related quality of life in active psoriatic arthritis: a randomized phase 2 trial (EQUATOR). Rheumatology (Oxford) 2020;59:1495-504.

48. Strand V, Mease PJ, Soriano ER, Kishimoto M, Salvarani C, Saffore CD, et al. Improvement in patient-reported outcomes in patients with psoriatic arthritis treated with upadacitinib versus placebo or adalimumab: results from SELECT-PsA 1. Rheumatol Ther 2021;8:1789-808.

49. Strand V, Van den Bosch F, Ranza R, Leung YY, Drescher E, Zueger P, et al. Patient-reported outcomes in psoriatic arthritis patients with an inadequate response to biologic disease-modifying antirheumatic drugs: SELECT-PsA 2. Rheumatol Ther 2021;8:1827-44.

50. Strand V, Tundia N, Bergman M, Ostor A, Durez P, Song IH, et al. Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE. Rheumatology (Oxford) 2021;60:5583-94.

51. Strand V, Schett G, Hu C, Stevens RM. Patient-reported health-related quality of life with apremilast for psoriatic arthritis: a phase II, randomized, controlled study. J Rheumatol 2013;40:1158-65.
52. Tälli S, Etcheto A, Fautrel B, Balanescu A, Braun J, Cañete JD, et al. Patient global assessment in psoriatic arthritis - what does it mean? An analysis of 223 patients from the psoriatic arthritis impact of disease (PsAID) study. Joint Bone Spine 2016;83:335-40.

53. Salaffi F, Di Carlo M, Carotti M, Farah S, Gutierrez M. The Psoriatic Arthritis Impact of Disease 12-item questionnaire: equivalence, reliability, validity, and feasibility of the touch-screen administration versus the paper-and-pencil version. Ther Clin Risk Manag 2016;12:631-42.
TABLES

<table><caption>Table 1. Baseline demographic and clinical characteristics*</caption><thead><tr><th>Parameter</th><th>Placebo<br>n=66</th><th>Deucravacitinib<br>6 mg QD<br>n=70</th><th>Deucravacitinib<br>12 mg QD<br>n=67</th></tr></thead><tbody><tr><td>Mean age, years</td><td>48.5</td><td>50.5</td><td>50.5</td></tr><tr><td>Female, n (%)</td><td>40 (60.6)</td><td>30 (42.9)</td><td>34 (50.7)</td></tr><tr><td>Mean BMI, kg/m<sup>2</sup></td><td>31.2</td><td>29.6</td><td>30.3</td></tr><tr><td>Disease duration since diagnosis, median<br>(range), years</td><td>4.5 (0.6-22.9)</td><td>5.3 (0.1-42.8)</td><td>3.8 (0.6-27.7)</td></tr><tr><td>Tender joint count, mean (SD)</td><td>16.9 (9.8)</td><td>18.1 (10.3)</td><td>19.4 (11.8)</td></tr><tr><td>Swollen joint count, mean (SD)</td><td>10.5 (7.7)</td><td>11.9 (7.0)</td><td>11.3 (9.0)</td></tr><tr><td>Patients with LEI score ≥1, n (%)</td><td>31 (47.0)</td><td>39 (55.7)</td><td>26 (38.8)</td></tr><tr><td>Psoriasis body surface area ≥3%, n (%)</td><td>54 (81.8)</td><td>59 (84.3)</td><td>52 (77.6)</td></tr><tr><td>PASI score at baseline in patients with BSA<br>≥3% at baseline, mean (range)</td><td>9.1 (1.2-31.4)</td><td>8.5 (1.6-33.8)</td><td>7.9 (1.4-31.8)</td></tr><tr><td>HAQ-DI, mean (SD)</td><td>1.3 (0.6)</td><td>1.3 (0.6)</td><td>1.3 (0.6)</td></tr><tr><td>FACIT-Fatigue, mean (SD)</td><td>29.5 (9.7)</td><td>29.0 (10.1)</td><td>28.1 (11.4)</td></tr><tr><td>Patient Global Assessment of Disease<br>Activity (PtGA), mean (SD)</td><td>66.2 (15.8)</td><td>68.2 (16.8)</td><td>63.6 (15.6)</td></tr><tr><td>Pain VAS, mean (SD)</td><td>64.9 (18.2)</td><td>63.6 (21.7)</td><td>63.8 (15.9)</td></tr><tr><td>SF-36 PCS score, mean (SD)</td><td>33.4 (7.5)</td><td>34.0 (8.0)</td><td>34.5 (7.0)</td></tr><tr><td>SF-36 MCS score, mean (SD)</td><td>47.5 (10.9)</td><td>45.4 (10.3)</td><td>46.9 (10.7)</td></tr><tr><td>SF-36 domain scores, mean (SD)</td><td></td><td></td><td></td></tr><tr><td>Physical functioning</td><td>42.4 (23.6)</td><td>41.9 (21.8)</td><td>44.1 (23.2)</td></tr><tr><td>Role-physical</td><td>42.8 (19.4)</td><td>42.9 (21.4)</td><td>46.0 (22.2)</td></tr><tr><td>Bodily pain</td><td>31.7 (15.5)</td><td>32.5 (16.0)</td><td>33.4 (14.9)</td></tr><tr><td>General health</td><td>40.3 (15.8)</td><td>39.6 (17.1)</td><td>38.5 (19.0)</td></tr><tr><td>Vitality</td><td>38.8 (17.3)</td><td>39.0 (15.7)</td><td>43.0 (19.3)</td></tr><tr><td>Social functioning</td><td>63.8 (23.7)</td><td>57.0 (21.6)</td><td>65.5 (23.9)</td></tr><tr><td>Role-emotional</td><td>75.1 (23.1)</td><td>69.5 (23.4)</td><td>71.5 (26.2)</td></tr><tr><td>Mental health</td><td>59.9 (20.3)</td><td>58.4 (18.5)</td><td>59.2 (19.8)</td></tr><tr><td>PsAID-12 score, mean (SD)</td><td>5.7 (1.7)</td><td>5.6 (1.8)</td><td>5.8 (1.6)</td></tr><tr><td>PsAID-12 item scores, mean (SD)</td><td></td><td></td><td></td></tr><tr><td>Pain</td><td>6.6 (1.8)</td><td>6.3 (2.0)</td><td>6.4 (1.5)</td></tr><tr><td>Fatigue</td><td>6.3 (2.0)</td><td>5.9 (2.2)</td><td>6.1 (1.8)</td></tr><tr><td>Skin problems</td><td>6.1 (2.6)</td><td>6.4 (2.4)</td><td>6.4 (2.5)</td></tr></tbody></table>
<table><tr><td>Work or leisure</td><td>5.9 (2.0)</td><td>5.7 (2.3)</td><td>5.7 (2.0)</td></tr><tr><td>Functional capacity</td><td>6.2 (2.0)</td><td>5.9 (2.2)</td><td>6.1 (2.0)</td></tr><tr><td>Discomfort</td><td>6.5 (2.0)</td><td>6.3 (2.3)</td><td>6.7 (1.7)</td></tr><tr><td>Sleep disturbance</td><td>4.9 (2.6)</td><td>5.0 (2.7)</td><td>5.7 (2.3)</td></tr><tr><td>Coping</td><td>5.5 (2.3)</td><td>5.2 (2.2)</td><td>5.4 (2.2)</td></tr><tr><td>Anxiety fear uncertainty</td><td>4.9 (2.7)</td><td>4.8 (2.9)</td><td>4.8 (2.9)</td></tr><tr><td>Embarrassment shame</td><td>4.9 (2.9)</td><td>4.9 (2.9)</td><td>5.0 (2.8)</td></tr><tr><td>Social participation</td><td>4.4 (2.8)</td><td>4.4 (2.9)</td><td>4.2 (2.8)</td></tr><tr><td>Depression</td><td>3.3 (2.8)</td><td>3.4 (2.8)</td><td>3.7 (3.2)</td></tr><tr><td>BASDAI, mean (SD)</td><td>6.3 (1.3)</td><td>5.4 (2.0)</td><td>5.9 (1.9)</td></tr></table>

*For additional demographics and baseline clinical characteristics, see Mease et al. 2022 (24).

BMI, body mass index; BSA, body surface area; csDMARD, conventional synthetic disease-modifying antirheumatic drug; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; LEI, Leeds Enthesitis Index; MCS, mental component summary; MTX, methotrexate; PASI, Psoriasis Area and Severity Index; PCS, physical component summary; PsAID, Psoriatic Arthritis Impact of Disease; QD, once daily; SD, standard deviation; SF-36, 36-Item Short-Form Health Survey; TNFi, tumor necrosis factor inhibitor; VAS, visual analog scale.
<table><caption>Table 2. Summary of changes from baseline in patient-reported outcomes at Week 16</caption><thead><tr><th>Parameter</th><th>Placebo<br>n=66</th><th>Deucravacitinib<br>6 mg<br>n=70</th><th>Deucravacitinib<br>12 mg<br>n=67</th></tr></thead><tbody><tr><td>HAQ-DI, adjusted change from baseline, mean (95% CI)</td><td>-0.11 (-0.24, 0.02)</td><td>-0.37 (-0.50, -0.24)</td><td>-0.39 (-0.53, -0.26)</td></tr><tr><td>FACIT-Fatigue, adjusted change from baseline, mean (95% CI)</td><td>2.8 (0.5, 5.1)</td><td>5.6 (3.4, 7.9)</td><td>7.2 (4.9, 9.5)</td></tr><tr><td>Patient Global Assessment of Disease Activity (PtGA), change from baseline, mean (SD)</td><td>-13.4 (23.5)</td><td>-28.7 (23.1)</td><td>-27.6 (25.8)</td></tr><tr><td>Pain VAS, change from baseline, mean (SD)</td><td>-13.8 (21.5)</td><td>-25.3 (26.1)</td><td>-27.5 (25.0)</td></tr><tr><td>SF-36 PCS score, adjusted change from baseline, mean (95% CI)</td><td>2.3 (0.4, 4.2)</td><td>5.6 (3.8, 7.5)</td><td>5.8 (3.9, 7.7)</td></tr><tr><td>SF-36 MCS score, adjusted change from baseline, mean (95% CI)</td><td>0.7 (-1.3, 2.7)</td><td>3.6 (1.7, 5.5)</td><td>3.5 (1.5, 5.5)</td></tr><tr><td colspan="4">SF-36 domain scores, least squares mean change from baseline (95% CI)</td></tr><tr><td>Physical functioning</td><td>3.3 (-1.8, 8.5)</td><td>14.6 (9.5, 19.6)</td><td>13.3 (8.1, 18.4)</td></tr><tr><td>Role-physical</td><td>5.3 (0.3, 10.3)</td><td>12.3 (7.4, 17.1)</td><td>13.5 (8.5, 18.5)</td></tr><tr><td>Bodily pain</td><td>7.0 (2.0, 12.0)</td><td>15.9 (11.0, 20.8)</td><td>19.5 (14.5, 24.6)</td></tr><tr><td>General health</td><td>6.2 (1.9, 10.6)</td><td>9.5 (5.2, 13.7)</td><td>8.4 (4.0, 12.8)</td></tr><tr><td>Vitality</td><td>4.2 (0.1, 8.4)</td><td>11.7 (7.7, 15.8)</td><td>12.1 (7.9, 16.3)</td></tr><tr><td>Social functioning</td><td>-0.2 (-5.4, 5.1)</td><td>13.2 (8.0, 18.3)</td><td>10.5 (5.2, 15.7)</td></tr><tr><td>Role-emotional</td><td>1.6 (-3.5, 6.8)</td><td>6.9 (1.9, 11.9)</td><td>8.7 (3.6, 13.9)</td></tr><tr><td>Mental health</td><td>3.6 (-0.2, 7.5)</td><td>8.1 (4.3, 11.8)</td><td>8.2 (4.3, 12.0)</td></tr><tr><td>PsAID-12, adjusted change from baseline, mean (95% CI)</td><td>-1.0 (-1.5, -0.5)</td><td>-2.1 (-2.6, -1.6)</td><td>-2.3 (-2.8, -1.7)</td></tr><tr><td colspan="4">PsAID-12 item scores, adjusted change from baseline, mean (95% CI)</td></tr><tr><td>Pain</td><td>-1.3 (-1.9, -0.7)</td><td>-2.3 (-2.8, -1.7)</td><td>-2.3 (-2.9, -1.7)</td></tr><tr><td>Fatigue</td><td>-1.1 (-1.7, -0.5)</td><td>-1.8 (-2.4, -1.2)</td><td>-2.0 (-2.6, -1.4)</td></tr><tr><td>Skin problems</td><td>-1.8 (-2.4, -1.1)</td><td>-2.4 (-3.0, -1.8)</td><td>-3.0 (-3.7, -2.4)</td></tr><tr><td>Work or leisure</td><td>-1.0 (-1.6, -0.5)</td><td>-2.2 (-2.8, -1.6)</td><td>-2.1 (-2.7, -1.5)</td></tr><tr><td>Functional capacity</td><td>-0.8 (-1.4, -0.3)</td><td>-2.2 (-2.7, -1.6)</td><td>-2.1 (-2.7, -1.5)</td></tr><tr><td>Discomfort</td><td>-1.1 (-1.7, -0.5)</td><td>-2.6 (-3.1, -2.0)</td><td>-2.6 (-3.3, -2.0)</td></tr><tr><td>Sleep disturbance</td><td>-0.9 (-1.5, -0.3)</td><td>-1.8 (-2.4, -1.2)</td><td>-2.1 (-2.7, -1.5)</td></tr><tr><td>Coping</td><td>-0.9 (-1.5, -0.3)</td><td>-2.0 (-2.6, -1.4)</td><td>-2.0 (-2.6, -1.4)</td></tr><tr><td>Anxiety fear uncertainty</td><td>-0.7 (-1.4, -0.1)</td><td>-1.9 (-2.5, -1.3)</td><td>-2.0 (-2.6, -1.4)</td></tr><tr><td>Embarrassment shame</td><td>-1.0 (-1.6, -0.3)</td><td>-2.0 (-2.7, -1.4)</td><td>-2.6 (-3.3, -1.9)</td></tr></tbody></table>
<table><tr><td>Social participation</td><td>-0.3 (-1.0, 0.3)</td><td>-1.7 (-2.3, -1.0)</td><td>-1.8 (-2.5, -1.2)</td></tr><tr><td>Depression</td><td>-0.4 (-1.0, 0.3)</td><td>-1.3 (-1.8, -0.7)</td><td>-1.6 (-2.2, -1.0)</td></tr><tr><td>BASDAI, adjusted change from baseline, mean (95% CI)</td><td>-1.7 (-2.8, -0.6)</td><td>-2.0 (-3.0, -1.0)</td><td>2.2 (-3.3, -1.0)</td></tr></table>

Positive changes indicate improvement in FACIT-Fatigue and SF-36 scores; negative changes indicate improvement in HAQ-DI, PtGA, Pain VAS, PsAID-12, and BASDAI scores.

BASDAI, Bath Ankylosing Spondylitis Disease Activity Index;CI, confidence interval; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; MCS, mental component summary; PCS, physical component summary; PsAID, Psoriatic Arthritis Impact of Disease; QD, once daily; SD, standard deviation; SF-36, 36-Item Short-Form Health Survey; VAS, visual analog scale.
FIGURES

<caption>Figure 1. (A) SF-36 domain and (B) PsAID-12 item scores at baseline and at Week 16.</caption>

A

<figure><img src="image_2.png" /></figure>
B

<figure><img src="image_3.png" /></figure>

P values reported are nominal.

A/S, age/sex; BP, bodily pain; DEUC, deucravacitinib; GH, general health; MH, mental health; NS, not significant; PF, physical functioning; PsAID, Psoriatic Arthritis Impact of Disease; QD, once daily; RE, role-emotional, RP, role-physical; SF, social functioning; SF-36, 36-Item Short-Form Health Survey; VT, vitality; Wk, week.
<figure><img src="image_4.png" /><figcaption>Figure 2. Percentage of patients reporting improvements from baseline at Week 16 with at least MCIDs in (A) patient-reported outcomes, (B) SF-36 domains A.</figcaption></figure>

B.

<figure><img src="image_5.png" /></figure>

†BASDAI was only calculated in patients with evidence of axial PsA involvement and Baseline BASDAI ≥4 by week. ‡Overall n=16. §Overall n=15. Nonresponder imputation method was used to impute missing data. BP, bodily pain; DEUC, deucravacitinib; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue; GH, general health; HAQ-DI, Health Assessment Questionnaire-Disability Index; MCID, minimum clinically important difference; MCS, mental component summary; MH, mental health; NNT, number needed to treat; PBO, placebo; PCS, physical component summary; PF, physical functioning; PRO, patient-reported outcome; PtGA, Patient Global Assessment of Disease Activity; QD, once daily; RE, role-emotional, RP, role-physical; SF, social functioning; SF-36, 36-Item Short-Form Health Survey; TNFi, tumor necrosis factor inhibitor; VAS, visual analog scale; VT, vitality.
<figure><img src="image_6.png" /><figcaption>Figure 3. Percentage of patients with (A) patient-reported outcome scores and (B) SF-36 domain scores of at least normative values* at baseline and at Week 16.</figcaption></figure>

Note: Nonresponder imputation method was used to impute missing data.

*Normative values for SF-36 domains: PF (≥81.1), RP (≥81.9), BP (≥72.5), GH (≥70.2), VT (≥59.1), SF (≥85.1), RE (≥88.0), MH (≥76.2).

BL, baseline; BP, bodily pain; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue; GH, general health; HAQ-DI, Health Assessment Questionnaire-Disability Index; MCS, mental component summary; MH, mental health; PCS, physical component summary; PF, physical functioning; PRO, patient-reported outcome; QD, once daily; RE, role-emotional, RP, role-physical; SF, social functioning; SF-36, 36-Item Short-Form Health Survey; VT, vitality; Wk, week.
<figure><img src="image_7.png" /><figcaption>Figure 4. Adjusted mean change from baseline in PsAID-12 scores at Week 16 in patient-reported outcome and select clinical outcome responders (A) and nonresponders (B). A.</figcaption></figure>

B.

<figure><img src="image_8.png" /></figure>

Response and non-response definitions are minimum clinically important difference from baseline and based on published literature.

FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; LDA, low disease activity; MCS, Mental Component Summary; PASDAS, Psoriatic Arthritis Disease Activity Score; PASI, Psoriasis Area and Severity Index; PBO, placebo; PCS, Physical Component Summary; PRO, patient-reported outcome; PsAID-12, 12-item Psoriatic Arthritis Impact of Disease questionnaire; PtGA, Patient Global Assessment; QD, once daily; SF-36, 36-item Short Form Health Survey; VAS, visual analog scale.

<footnote>*P ≤ 0.05 vs placebo.</footnote>

<footnote>† *P* ≤ 0.001 vs placebo.</footnote>
SUPPLEMENTARY MATERIAL

<table><caption>Supplemental Table S1. Spearman correlations at baseline and at Week 16 between PsAID-12 scores and comparative health outcomes</caption><thead><tr><th>Comparative measure</th><th>health PsAID-12 baseline</th><th>correlation - PsAID-12 Week 16</th></tr></thead><tbody><tr><td>Physician Global VAS</td><td>0.29</td><td>0.60</td></tr><tr><td>Patient Pain VAS</td><td>0.58</td><td>0.84</td></tr><tr><td>Patient Global VAS</td><td>0.64</td><td>0.87</td></tr><tr><td>HAQ-DI Total Score</td><td>0.58</td><td>0.63</td></tr><tr><td>FACIT-Fatigue</td><td>-0.59</td><td>-0.70</td></tr><tr><td>SF-36 PCS</td><td>-0.46</td><td>-0.61</td></tr><tr><td>SF-36 MCS</td><td>-0.40</td><td>-0.49</td></tr><tr><td>PsAID-9</td><td>0.99</td><td>0.996</td></tr></tbody></table>

<figure><img src="image_9.png" /></figure>

FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index-Fatigue; MCS, Mental Component Summary; PCS, Physical Component Summary; PsAID-12, 12-item Psoriatic Arthritis Impact of Disease questionnaire; SF-36, 36-item Short Form Health Survey; VAS, visual analog scale.