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Abstract
Objective Deucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved in multiple countries for the treatment of adults with moderate to severe plaque psoriasis. Deucravacitinib inhibits TYK2-mediated signaling of cytokines, such as type 1 interferons, involved in systemic lupus erythematosus (SLE). In the 48-week, double-blind, phase 2 PAISLEY trial in patients with active SLE (NCT03252587), all primary and secondary endpoints were met at the 3 mg twice-daily (BID) deucravacitinib dose, including SLE Responder Index-4 (SRI[4]) response rates vs placebo at weeks 32 (primary endpoint) and 48. Week 32 response rates were 34.4% vs 58.2%, 49.5%, and 44.9% with placebo vs deucravacitinib 3 mg BID, 6 mg BID, and 12 mg once daily (QD), respectively. This exploratory analysis assessed the efficacy of deucravacitinib according to patient baseline characteristics.
Methods In the PAISLEY trial, patients with active SLE were randomized 1:1:1:1 to receive placebo (n=90) or deucravacitinib 3 mg BID (n=91), 6 mg BID (n=93), or 12 mg QD (n=89). SRI(4) response rates at week 32 in the phase 2 PAISLEY trial were evaluated according to select baseline demographics and disease characteristics. Point estimates for response rates with asymptotic CIs were calculated for each treatment arm within each subgroup. All analyses were descriptive.
Results SRI(4) response rates in most analyzed subgroups were consistent with the observed response rates in the overall population and favored the 3 mg BID deucravacitinib dose. SRI(4) response rates in subgroups defined by race, baseline SLEDAI-2K and glucocorticoid dose, and years since initial diagnosis are provided below (figure 1). Of these, Black/African American race, other race, baseline SLEDAI-2K of <10, baseline glucocorticoid dose of ≥10 mg/day, and 3–6 and ≥6 years since diagnosis showed the greatest difference in SRI(4) responses for those receiving deucravacitinib vs placebo.
Conclusion Deucravacitinib was associated with improved SRI(4) response rates at week 32 across race, SLEDAI-2K, glucocorticoid dose, and years since diagnosis at baseline subgroups. Data interpretation for some subgroups was limited by low patient numbers. These findings support the efficacy of deucravacitinib in the treatment of patients with active SLE, regardless of patient baseline characteristics.
SRI(4) response rates at week 32 for selected baseline demographics and disease characteristics
Acknowledgements We 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 SciMentum, Inc, a Nucleus Group Holdings, Inc, company, and funded by Bristol Myers Squibb.
COI Disclosures
EM: Research support: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, and UCB; Consultancy: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, Novartis, and Servier
CA: Grant support: AstraZeneca and Bristol Myers Squibb; Advisor or review panel: AstraZeneca, Aurinia, Bristol Myers Squibb, GSK, and Kezar; Speaker/honoraria: AstraZeneca and Aurinia
LGP: Consultancy: Aurinia and Bristol Myers Squibb
AC: Research support: AstraZeneca and GSK; Consultancy/Speaker: AstraZeneca and GSK; Consultancy: Bristol Myers Squibb, Otsuka, and Roche
SP, CH, TW, and SB: Employees and shareholders: Bristol Myers Squibb
RK: Employee of Syneos Health, providing statistical services to Bristol Myers Squibb
RvV: Research support: Bristol Myers Squibb, GSK, and Eli Lilly; Research support, consultancy, and speaker: UCB; Support for educational programs, consultancy, and speaker: Pfizer; Support for educational programs: Roche; Consultancy and speaker: AbbVie, Galapagos, and Janssen; Consultancy: AstraZeneca, Biogen, Biotest, Celgene, Gilead, and Servier
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