POS0198 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS FROM A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Background: Tyrosine kinase 2 (TYK2) is an intracellular that mediates signaling by key cytokines involved in psoriatic arthritis (PsA) and plaque psoriasis (PsO) pathogenesis. Deucravacitinib a novel oral agent selectively inhibits TYK2 via allosteric mechanism binding to the nonconserved regulatory domain of kinase. A previous Phase trial PsO had demonstrated deucravacitinib was efficacious well tolerated, with no laboratory abnormalities observed. Objectives: To evaluate efficacy safety active PsA. Methods: This ongoing, 1-year, randomized, double-blind, placebo (PBO)-controlled (initial 16 weeks), multiregional, ( NCT03881059 ). Eligible patients PsA diagnosis for ≥6 months, met CASPAR criteria, disease ≥3 tender swollen joints, C-reactive protein mg/L (ULN, 5 mg/L), ≥1 lesion (≥2 cm). Patients failed or were intolerant nonsteroidal anti-inflammatory drug, corticosteroid, conventional synthetic disease-modifying antirheumatic drug (csDMARD), and/or 1 TNF inhibitor (TNFi; ≤30%). randomized 1:1:1 6 mg once daily (QD) 12 QD, PBO. The primary endpoint achievement ACR 20 response at Week 16. Additional endpoints included proportion achieving 50/70 response, Health Assessment Questionnaire-Disability Index (HAQ-DI) (≥0.35 improvement from baseline), enthesitis resolution (Leeds score 0), minimal activity, change baseline SF-36 physical component (SF-36 PCS) mental MCS), Psoriasis Area Severity (PASI) 75 adverse events (AEs), parameters. Results: Of 203 180 (89%) completed weeks treatment (deucravacitinib 63/70 [90%]; 59/67 [88%]; PBO, 58/66 [88%]). Demographic characteristics similar across groups. Mean age 49.8 years, 51% female, median duration 4.5 66% used csDMARDs throughout study, 15% TNFi. study its endpoint, QD demonstrating significantly higher responses versus PBO (Figure 1). also Adjusted mean changes PCS MCS 16, respectively, group (5.6 vs 2.3, P =0.0062; 3.6 0.7, =0.0211) (5.8 =0.0042; 3.5 =0.0263) compared PASI groups ≤0.0136 PBO). most common AEs mg/12 mg/PBO groups, during 16-week period nasopharyngitis (5.7%/17.9%/7.6%), sinusitis (0%/7.5%/0%), headache (7.1%/1.5%/4.5%), rash (4.3%/6.0%/0%). No serious AEs, herpes zoster infections, opportunistic thrombotic reported deucravacitinib-treated this period. Additionally, significant hematologic parameters (lymphocytes, neutrophils, platelets, hemoglobin) serum lipids observed treatment. Conclusion: over Treatment generally tolerated parameter profile consistent earlier trial. Acknowledgements: sponsored Bristol Myers Squibb. Professional medical writing assistance provided Peloton Advantage, LLC, OPEN company, funded Disclosure Interests: Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, UCB, Grant/research support from: Atul Deodhar Celgene, Glaxo Smith & Kline, Désirée van der Heijde Astellas, AstraZeneca, Bayer, Cyxone, Daiichi, Eisai, Merck, Regeneron, Roche, Sanofi, Takeda, UCB Frank Behrens Genzyme, Boehringer, MSD, Chugai, Alan Kivitz Shareholder Gilead Sciences, Inc., Paid Consultant: Flexion, Pharma Advanced Research, Speakers bureau: Jonghyeon Kim Employee Shalabh Singhal Miroslawa Nowak Subhashis Banerjee Squibb