OP0095 Efficacy and safety of deucravacitinib up to week 52 from POETYK PsA-2: a multicenter, randomized, double-blind, placebo-controlled, phase 3 study in patients with psoriatic arthritis

Background: Deucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor under investigation for the treatment of active psoriatic arthritis (PsA) in the randomized, double-blind, 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 4 years of long-term data [1], and is approved in multiple countries for this indication. Here, we report results up to week 52 from POETYK PsA-2. Objectives: To investigate the efficacy and safety of deucravacitinib in adults with active PsA who are naive to biologic disease-modifying antirheumatic drugs, are TNF inhibitor (TNFi) naive, or have experienced failure of or are intolerant of ≤ 2 prior TNFis taken for PsA or PsO. Methods: Patients met CASPAR criteria and had a PsA diagnosis for ≥ 3 months, active or documented history of plaque PsO, active arthritis (ie, ≥ 3 swollen and ≥ 3 tender joints), and a high-sensitivity C-reactive protein (hsCRP) level of ≥ 3 mg/L at screening. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR 20) at week 16. Key secondary endpoints included assessments of the musculoskeletal system, skin, and PsA disease activity measures and quality of life vs placebo at week 16. Patients were randomized 3:3:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily (safety reference arm) through week 16. From weeks 16 to 52, those randomized to deucravacitinib or apremilast continued treatment, while those receiving placebo were switched to deucravacitinib. Multiplicity-controlled hierarchical testing was used to assess primary and key secondary endpoints (week 16). Efficacy was analyzed using nonresponder imputation for missing binary data and control-based pattern imputation for missing continuous data. Safety was evaluated up to week 52. Results: Of 729 randomized patients, 312 received deucravacitinib, 312 received placebo, and 105 received apremilast. Demographics and baseline disease characteristics were balanced across groups. Mean disease duration since diagnosis was 5.35 years (range, 0.2–39.8 years); 30.2% of patients had an hsCRP level of ≥ 10 mg/L, 62.8% were receiving conventional synthetic disease-modifying antirheumatic drugs at baseline, and 13.4% were previously treated with a TNFi. At week 16, ACR 20 was achieved in significantly more patients treated with deucravacitinib than placebo (54.2% vs 39.4%; P = 0.0002), with similar trends for ACR 50 (28.8% vs 16.3%) and ACR 70 (10.6% vs 5.4%) (Figure 1). Response rates continued to improve beyond week 16 and were maintained through week 52. While no prespecified comparative statistical analyses were planned, apremilast efficacy data are also reported (Figure 1). Achievement of key secondary endpoints, including ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI 75; 40.9% vs 15.4%; P < 0.0001) and minimal disease activity (MDA; 25.6% vs 14.7%; P = 0.0007), was significantly greater with deucravacitinib vs placebo. Patients treated with deucravacitinib had greater mean change from baseline in Health Assessment Questionnaire Disability Index score (HAQ-DI; −0.3246 vs −0.2120; P = 0.0013) and 36-Item Short Form Survey physical component score (SF-36 PCS; 5.838 vs 3.796; P = 0.0002). Prespecified pooled analyses from POETYK PsA-1 and PsA-2 for enthesitis and dactylitis resolution showed that enthesitis resolution rates were 50.3% with deucravacitinib vs 45.1% with placebo ( P = 0.1781); higher rates of dactylitis resolution were seen with deucravacitinib vs placebo (57.6% vs 44.1%; nominal P = 0.0100). A numerical improvement in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-Fatigue) score was seen with deucravacitinib vs placebo (2.5 vs 1.8; P = 0.2017). Mean change from baseline in 28-joint Disease Activity Score - C-reactive protein (DAS28-CRP) was greater with deucravacitinib vs placebo (−1.277 vs −0.801; nominal P < 0.0001). Few serious adverse events (AEs; placebo, 1.0%; deucravacitinib, 1.9%; apremilast, 3.8%) and discontinuations due to AEs (1.3%; 2.2%; 10.5%) occurred through week 16. Deucravacitinib was well tolerated through week 52 (Table 1). Similar rates of major adverse cardiovascular events, venous thromboembolic events, opportunistic infections, and malignancies were observed with deucravacitinib, placebo, and apremilast throughout the study. Conclusion: Deucravacitinib, the first oral TYK2 inhibitor evaluated in a phase 3 PsA study, showed superior efficacy vs placebo across multiple endpoints at week 16, including musculoskeletal and dermatologic manifestations, overall disease activity measures, and quality of life in adults with active PsA. Clinical responses were maintained through week 52. Safety was consistent with the established deucravacitinib safety profile observed in the phase 2 PsA study and across the PsO clinical program [1-4]; no new safety signals were identified. These data reinforce deucravacitinib efficacy in PsA and underscore the favorable safety profile of deucravacitinib as a selective TYK2 inhibitor. REFERENCES: [1] Armstrong A, et al. Oral presentation at the EADV Symposium; May 16-18, 2024; St Julian's, Malta. Abstract 1333. [2] Mease PJ, et al. Ann Rheum Dis 2022;81:815–822. [3] Strober B, et al. J Am Acad Dermatol 2023;88:40–51. [4] Armstrong A, et al. J Am Acad Dermatol 2023;88:23–37. Figure 1 Table 1 . 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: Philip J. Mease AbbVie, ACELYRIN, Amgen, Bristol Myers Squibb, Century, Cullinan, Eli Lilly, Janssen, MoonLake Pharma, Novartis, Pfizer, and UCB, AbbVie, ACELYRIN, Amgen, Bristol Myers Squibb, Century, Cullinan, Eli Lilly, Janssen, MoonLake Pharma, Novartis, Pfizer, and UCB, AbbVie, ACELYRIN, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Vinod Chandran AbbVie, Bristol Myers Squibb, Eli Lilly, Pfizer, Regeneron, and Sanofi, AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Apogee, Arcutis, Arena, ASLAN, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, CTI BioPharma, Dermavant, EcoR1, Eli Lilly, Escient, Evelo Biosciences, Evommune, Forte Biosciences, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo Pharma, Lipidio, Merck, Nektar, Novartis, Pfizer, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB, Union, Ventyx Biosciences, Vibliome, and Xencor, AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly, Evelo Biosciences, Evommune, Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB, and Ventyx Biosciences, April W. Armstrong Boehringer Ingelheim/Parexel, Celgene, Dermavant, Genentech, GSK, Menlo Therapeutics, Merck, Modernizing Medicine, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Science 37, Sun Pharma, and Valeant;, AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, and Novartis Grants: Dermira, Kyowa Hakko Kirin, and UCB, outside the submitted work, Ricardo Blanco AbbVie, Pfizer, Roche, Lilly, Bristol Myers Squibb, Janssen, Galapagos and MSD, AbbVie, Pfizer, Roche, Lilly, Bristol Myers Squibb, Janssen and MSD, AbbVie, MSD, and and Roche, Alexis Ogdie AbbVie, Amgen, Bristol Myers Squibb, Celgene, Corona, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Pfizer to Penn, Novartis to Penn, and Amgen to Forward/NDB royalties: Novartis to husband, Evan Siegel AbbVie, Janssen, Bristol Myers Squibb, UCB, and Amgen/Horizon, AbbVie, Janssen, Bristol Myers Squibb, UCB, and Amgen/Horizon, Alice B. Gottlieb Amgen, Eli Lilly, Highlight Therapeutics, Janssen, Novartis, Sanofi, Sun Pharma, Takeda, Teva, UCB, XBiotech (stock options for RA), Amgen, Eli Lilly, Highlight Therapeutics, Janssen, Novartis, Sanofi, Sun Pharma, Takeda, Teva, UCB, Bristol Myers Squibb, Janssen, Moonlake, and UCB Pharma, (all paid to Mount Sinai School of Medicine), Xiaofeng Zeng: None declared, Diamant Thaçi AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Johnson & Johnson, Leo Pharma, L'Oreal, MoonLake Pharma, Novartis, Pfizer, La Roche-Posay, Sanofi, Regeneron, Sun-Pharma, Target RWE, UCB and Vichy, AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Johnson & Johnson, Leo Pharma, L'Oreal, MoonLake Pharma, Novartis, Pfizer, La Roche-Posay, Sanofi, Regeneron, Sun-Pharma, Target RWE, UCB and Vichy, AbbVie, Almirall, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen-Cilag, Leo Pharma, MoonLake Pharma, Novartis, Pfizer, Regeneron, Sanofi and UCB, Mitsumasa Kishimoto AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Novartis, Tanabe-Mitsubishi, and UCB, AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Novartis, Tanabe-Mitsubishi, and UCB, Hendrik Schulze-Koops Lecturer: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz-Hexal, Sanofi, and UCB, AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Galapagos, Novartis, Pfizer, and UCB;, AbbVie, Amgen, Biogen Idec, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, GSK, Janssen-Cilag, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz-Hexal, Sanofi, and UCB, Alan Kivitz AbbVie, Excel Continuing Education, Lilly, Pfizer, and Sanofi – Regeneron; Speaker bureau: AbbVie, GSK, Sanofi – Regeneron, and UCB; Educational: Prime; Advisory board: Fresenius Kabi, Janssen, Takeda – Nimbus, and UCB; Scientific expert: Genzyme, Pfizer, GSK, Gilead, Novartis, and Amgen, AbbVie, Coval, Ecor1, Fresenius Kabi, Gilead, Grunenthal, GSK, Halia, Horizon, Innovaderm, Janssen, Moonlake Pharma, Pacira, Prometheus, Santa Ana Bio, Inc., Synact, Takeda – Nimbus, UCB, VYNE, XBiotech, and Xencor, Eva Dokoupilova: None declared, Akimichi Morita AbbVie, Amgen, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly Japan, Janssen Pharmaceutical, Kyowa Kirin, LEO Pharma, Maruho, Sun Pharma Japan, Taiho Pharmaceutical, Torii Pharmaceutical, UCB Japan, and Ushio, AbbVie, Amgen, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly Japan, Janssen Pharmaceutical, Kyowa Kirin, LEO Pharma, Maruho, Sun Pharma Japan, Taiho Pharmaceutical, Torii Pharmaceutical, UCB Japan, and Ushio, AbbVie, Amgen, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly Japan, Janssen Pharmaceutical, Kyowa Kirin, LEO Pharma, Maruho, Sun Pharma Japan, Taiho Pharmaceutical, Torii Pharmaceutical, UCB Japan, and Ushio, Eric Ruderman AbbVie, Bristol Myers Squibb, Janssen, Novartis, Merck, NS Pharma, Selecta, and UCB, SetPoint and Sonoma Bioscience, Michael Plewinski Bristol Myers Squibb, Bristol Myers Squibb, Kejia Wang Bristol Myers Squibb, Bristol Myers Squibb, Caroline Sardinas Bristol Myers Squibb, Bristol Myers Squibb, James Thielke Bristol Myers Squibb, Bristol Myers Squibb, Eleni Vritzali Bristol Myers Squibb, Bristol Myers Squibb, John Vaile Bristol Myers Squibb, Bristol Myers Squibb, Atul Deodhar Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, Novartis, Pfizer, and UCB, Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, MoonLake Pharma, Novartis, Pfizer, and UCB. © The Authors 2025. 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