Pos0527 Deucravacitinib, a First-in-Class, Oral, Selective, Allosteric Tyrosine Kinase 2 (Tyk2) Inhibitor, in Systemic Lupus Erythematosus (Sle): Efficacy by Baseline Demographics and Disease Characteristics in the Phase 2 Paisley Trial

Background: 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. Deucravacitinib selectively inhibits TYK2-mediated signaling of certain cytokines, such as type I interferons, involved in SLE. The 48-week, double-blind, phase 2 PAISLEY trial (NCT03252587) of deucravacitinib in patients with active SLE met its primary and secondary endpoints, with deucravacitinib 3 mg twice daily (BID) demonstrating superiority to placebo in the primary endpoint of SLE Responder Index-4 (SRI[4]) response at week 32 and all secondary endpoints at week 48.¹ Objectives: To evaluate the efficacy of deucravacitinib 3 mg BID vs placebo at week 48 by baseline demographics and disease characteristics in subgroups of patients in the PAISLEY trial. Methods: Patients with active SLE were randomized 1:1:1:1 to placebo (n = 90) or deucravacitinib 3 mg BID (n = 91), 6 mg BID (n = 93), or 12 mg once daily (n = 89). Key secondary endpoints were assessed at week 48 in the PAISLEY trial, including SRI[4] response rate, British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response rate, a ≥ 50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (CLASI-50) in patients with a CLASI activity score of ≥ 10 at baseline, and a ≥ 50% reduction in active (swollen + tender) joint count (JC-50) from baseline in patients with an active 40-joint count of ≥ 6 at baseline. Response rates were reported with a prespecified nonresponder imputation method for missing values or patients who took prespecified prohibited medications;¹ the 2-sided 95% CI was based on the asymptotic (including continuity correction) method. For each secondary endpoint, response rates were analyzed according to baseline demographics and disease characteristics, including race, glucocorticoid (GC) use, baseline SLE Disease Activity Index-2000 (SLEDAI-2K) score, and disease duration. The 3 mg BID dose generated the optimal benefit-risk profile vs placebo; therefore, for this analysis, this dose was determined to be representative of the efficacy of the drug. All analyses were conducted post hoc and were descriptive. Results: Baseline demographics and disease characteristics were well balanced between the placebo and treatment arms. Overall, SRI[4] and BICLA response rates increased with deucravacitinib 3 mg BID vs placebo at week 48, regardless of patient race, GC use at baseline, baseline SLEDAI-2K score, or disease duration (Figure 1). Similarly, CLASI-50 and JC-50 response rates increased with deucravacitinib 3 mg BID vs placebo in these subgroups (Figure 2). Data interpretation for some subgroups was limited by low patient numbers. Conclusion: In the phase 2 PAISLEY trial, deucravacitinib 3 mg BID was associated with improved SRI[4], BICLA, CLASI-50, and JC-50 response rates at week 48 in multiple patient subgroups with select baseline demographics and disease characteristics. These findings will be validated in the ongoing phase 3 trials of deucravacitinib in SLE. REFERENCES: [1] Morand E, et al. Arthritis Rheumatol 2023;75:242–252. Acknowledgements: We would like to thank the patients and their families who made this study possible, as well as the clinical teams who participated. This study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Angela R. Eder, PhD, of Nucleus Global, and funded by Bristol Myers Squibb. Disclosure of Interests: Eric Morand AstraZeneca, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Gilead, Novartis, and Takeda, AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, Takeda, and UCB, Cristina Arriens AstraZeneca, Aurinia, AstraZeneca, Aurinia, Bristol Myers Squibb, GSK, Kezar, AstraZeneca and Bristol Myers Squibb, Laura Geraldino-Pardilla Aurinia, Bristol Myers Squibb, Ann E. Clarke Bristol Myers Squibb, Otsuka, Roche, AstraZeneca, GSK, Samantha Pomponi Bristol Myers Squibb, Bristol Myers Squibb, Coburn Hobar Bristol Myers Squibb, Bristol Myers Squibb, Thomas Wegman Bristol Myers Squibb, Bristol Myers Squibb, Ravi Koti Syneos Health, providing statistical services to Bristol Myers Squibb, Subhashis Banerjee Bristol Myers Squibb, Bristol Myers Squibb, Ronald F. van Vollenhoven Pfizer, Roche, Pfizer, AbbVie, Galapagos, Janssen, UCB, AbbVie, Galapagos, Janssen, AstraZeneca, Biogen, Biotest, Celgene, Gilead, Servier, Bristol Myers Squibb, GSK, Eli Lilly, UCB, Pfizer.