LB0001 EFFICACY AND SAFETY OF DEUCRAVACITINIB UP TO WEEK 16 FROM POETYK PsA-1: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 STUDY IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS

Background: Deucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor investigated for the treatment of active psoriatic arthritis (PsA) in the global, randomized, double-blind, placebo-controlled, phase 3 POETYK PsA-1 (NCT04908202) and PsA-2 (NCT04908189) studies. Deucravacitinib has an established clinical profile in moderate to severe plaque psoriasis (PsO), with over 5 years of long-term data [1], and is approved in multiple countries for this indication. Here, we report primary outcomes up to W16 from the POETYK PsA-1 phase 3 study, evaluating the use of the first TYK2 inhibitor in PsA. Objectives: To assess the efficacy and safety of deucravacitinib in adults with active PsA who are naive to biologic disease-modifying antirheumatic drugs (bDMARDs). Methods: Patients had a PsA diagnosis for ≥ 3 months; met CASPAR criteria; and had active or documented PsO, active arthritis (≥ 3 swollen and ≥ 3 tender joints), a high-sensitivity C-reactive protein (hsCRP) level of ≥ 3 mg/L, and ≥ 1 PsA-related hand and/or foot joint erosion on radiographs at screening (ie, at high risk for radiographic progression). The primary endpoint was ACR 20 at W16. Key secondary endpoints comprised assessments of PsA disease activity measures, joint and skin clinical responses, radiographic progression, and quality of life (QoL). Analyses for primary and key secondary endpoints (W16) were controlled for multiplicity, with nonresponder imputation used for missing binary data and control-based pattern imputation used for missing continuous data. The prespecified radiographic analysis used parametric ANCOVA for mean change from baseline (CfB) in modified Sharp-van der Heijde (mSvdH) total score and included randomized patients with W16 scans performed during the analysis window between days 100 to 127 and before the first dose in the active treatment period. Data were imputed for patients with missing W16 scans or with out-of-window baseline (prior to day −38 or after day −1) or W16 scans. Due to nonnormal radiographic data distribution, 2 post hoc analyses were performed using nonparametric rank ANCOVA, without imputation for missing data: (1) in the population with prespecified windowing rules and (2) in a population with windowing rules removed (ie, all available radiographic assessments [except 4 early terminations]). Safety was evaluated. Results: Among 670 randomized patients, 336 received deucravacitinib 6 mg QD, and 334 received placebo. Demographics and baseline disease characteristics were generally balanced between groups. ACR 20 was achieved in significantly more patients treated with deucravacitinib vs placebo at W16 (54.2% vs 34.1%; P < 0.0001), with similar results for ACR 50 and ACR 70 (Table 1). ACR 20 responses were consistent, regardless of concomitant use of conventional synthetic DMARDs or hsCRP level at baseline. Statistically significant differences were met for the key secondary endpoints of HAQ-DI, PASI 75, SF-36 PCS, and MDA, with nominally significant differences for FACIT-Fatigue, dactylitis resolution, and DAS28-CRP (Table 1). While the prespecified radiographic analysis did not show a statistically significant difference in mean CfB in mSvdH score between deucravacitinib and placebo (Table 1), results from the post hoc nonparametric radiographic analysis in the same population were statistically significant for deucravacitinib vs placebo; when all available radiographic assessments were analyzed, a statistically significant difference between groups was observed (Table 1). Significantly greater proportions of patients treated with deucravacitinib did not have radiographic progression (CfB to W16 in mSvdH score ≤ 0) vs placebo in both populations. The only adverse event (AE) occurring in ≥ 5% in either arm was upper respiratory tract infection (deucravacitinib, 5.1%; placebo, 3.0%). Serious AEs (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (deucravacitinib, 2.4%; placebo, 1.8%) were infrequent through W16 (Table 2). There were no safety signals related to major adverse cardiovascular events, venous or arterial thromboembolic events, malignancies, or opportunistic infections observed with deucravacitinib. Conclusion: Treatment with deucravacitinib, the first oral TYK2 inhibitor evaluated in phase 3 studies of active PsA, resulted in superior efficacy vs placebo at W16 across multiple endpoints, including overall disease activity measures, musculoskeletal and dermatologic manifestations, and QoL in adults with active PsA who were naive to bDMARDs. Inhibition of radiographic progression was observed with deucravacitinib at W16 in post hoc analyses. Safety was consistent with the established safety profile of deucravacitinib in the phase 3 POETYK PsA-2 study, the phase 2 PsA study, and across the PsO clinical program,p [1, 2, 3, 4, 5] with no new safety signals identified. Findings demonstrate deucravacitinib efficacy in PsA and underscore its favorable safety profile. REFERENCES: [1] Armstrong AW, et al. SKIN The Journal of Cutaneous Medicine 2025;9:s532. [2] Mease PJ, et al. Oral presentation at the 2025 AAD Annual Meeting; March 7–11, 2025; Orlando, FL, USA. Presentation 66894. [3] Mease PJ, et al. Ann Rheum Dis 2022;81:815–822. [4] Strober B, et al. J Am Acad Dermatol 2023;88:40–51. [5] Armstrong A, et al. J Am Acad Dermatol 2023;88:23–37. Acknowledgements: We thank the patients and families who made this study possible, as well as the clinical teams that participated. The study was supported by Bristol Myers Squibb. All authors contributed to and approved the abstract; professional medical writing and editorial assistance was provided by Stephanie V. Koebele, PhD, of Nucleus Global, funded by Bristol Myers Squibb. Disclosure of Interests: Désirée van der Heijde Consulting fees: AbbVie, Alfasigma, argenx, Bristol Myers Squibb, Eli Lilly, Grey-Wolf Therapeutics, Janssen, Novartis, Pfizer, Takeda, and UCB Pharma. Associate editor: Annals of the Rheumatic Diseases. Editorial board member: Journal of Rheumatology. Director of Imaging Rheumatology bv., Philip J. Mease Consulting and/or speaker fees: AbbVie, ACELYRIN, Amgen, Bristol Myers Squibb, Century, Cullinan, Eli Lilly, Janssen, MoonLake Pharma, Novartis, Pfizer, and UCB, Research grants: AbbVie, ACELYRIN, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Carle Paul Consultant: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Mylan, Novartis, Pfizer, Sandoz, and UCB, Grants: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Mylan, Novartis, Pfizer, Sandoz, and UCB, Frank Behrens: None declared, Laure Gossec Consulting fees: AbbVie, Alfasigma, Amgen, BMS, Celltrion, Johnson & Johnson, Lilly, MoonLake Pharma, Novartis, Pfizer, STADA, and UCB, Research grants: AbbVie, Lilly, Novartis, and UCB, Yuko Kaneko Consultant: Bristol Myers Squibb; Lecture honorarium: Bristol Myers Squibb, Lihi Eder Advisory boards: AbbVie, Novartis, UCB, Pfizer, Eli Lilly, and Janssen, Research and educational grants: AbbVie, Novartis, UCB, Pfizer, Sandoz, Fresenius Kabi, Eli Lilly, and Janssen, Laura C. Coates Speaker: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultancy: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Enlivex, Janssen, MoonLake Pharma, Novartis, Pfizer, Takeda and UCB, Grants/research support: AbbVie, Amgen, Janssen and UCB, Andrew Pink: None declared, Weiguo Wan: None declared, Enrique R. Soriano: None declared, Piotr Leszczyński Speaker fees: Novartis, AbbVie, AstraZeneca, Bristol Myers Squibb, Pfizer, and UCB, Research support: Bristol Myers Squibb, Jose U. Scher: None declared, Atul Deodhar Consulting and/or advisory boards: Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, Novartis, Pfizer, and UCB, Research grants: Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, MoonLake Pharma, Novartis, Pfizer, and UCB, Chahin Pachai Shareholder: Bristol Myers Squibb, Employee: Bristol Myers Squibb, Shimon Korish Shareholder at the time of study conduct: Bristol Myers Squibb, Employee at the time of study conduct: Bristol Myers Squibb, Adaora Enemuo Shareholder: Bristol Myers Squibb, Employee: Bristol Myers Squibb, Sahar Rabbat Shareholder: Bristol Myers Squibb, Employee: Bristol Myers Squibb, Min Wang Shareholder: Bristol Myers Squibb, Employee: Bristol Myers Squibb, Eleni Vritzali Shareholder: Bristol Myers Squibb, Employee: Bristol Myers Squibb, John Vaile Shareholder: Bristol Myers Squibb, Employee: Bristol Myers Squibb, Joseph F. Merola Consultant and/or investigator: AbbVie, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Janssen, LEO Pharma, MoonLake Pharma, Novartis, Pfizer, Sanofi-Regeneron, Sun Pharma, and UCB. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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