AB0891 Deucravacitinib Efficacy in Psoriatic Arthritis by Baseline DMARD Use: Exploratory Analysis From a Phase 2 Study

Abstract

BackgroundPsoriatic arthritis (PsA) treatment guidelines recommend that patients (pts) inadequately responding to conventional synthetic DMARDs (csDMARDs) can be treated with targeted synthetic DMARDs with or without background use of csDMARDs. Deucravacitinib (DEUC) is a novel, oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2) that binds to the unique TYK2 regulatory domain, thereby suppressing signaling of key cytokines (eg, IL-23) involved in PsA pathogenesis. In a Phase 2 trial in pts with active PsA, DEUC was well tolerated and significantly more efficacious than placebo (PBO) after 16 weeks of treatment.1ObjectivesThis analysis further evaluated the effect of DEUC in this Phase 2 trial in pts treated with and without background csDMARDs for 16 weeks.MethodsThis double-blind trial (NCT03881059) enrolled pts with active PsA who had either failed or were intolerant to ≥1 nonsteroidal anti-inflammatory drug, corticosteroid, csDMARD, and/or 1 TNF inhibitor (TNFi; up to 30%). Pts were randomised 1:1:1 to DEUC 6 mg once daily (QD) or 12 mg QD, or PBO. A post hoc subgroup analysis in pts with and without background csDMARD use assessed improvements in select clinical outcomes (ACR 20 response, and change from baseline in ACR components, Psoriasis Area and Severity Index total score, and Psoriatic Arthritis Disease Activity Score) at Week 16.ResultsBaseline (BL) demographics, clinical characteristics, and disease activity were generally similar among pts with and without background csDMARD use. At BL, background csDMARD use was 64.3%, 64.2%, and 66.7% and methotrexate use was 50.0%, 55.2%, and 59.1% in the DEUC 6 mg QD, 12 mg QD, and PBO groups, respectively. Pts with and without background csDMARD use showed similar improvements at Week 16 with DEUC treatment versus PBO on most clinical measures, pt-reported outcomes, and composite measures (Table 1 and Figure 1). No clinically meaningful differences in adverse events (AEs) were observed in pts with or without background csDMARD use.Table 1.Adjusted mean (SE) change from baseline at Week 16 in clinical outcomes by csDMARD usePBO w/o csDMARD (n=22)PBO w csDMARD (n=44)DEUC 6 mg QD w/o csDMARD (n=25)DEUC 6 mg QD w csDMARD (n=45)DEUC 12 mg QD w/o csDMARD (n=24)DEUC 12 mg QD w csDMARD (n=43)Swollen joint count-4.7 (1.4)-5.0 (0.9)-7.4 (1.4)-6.8 (0.9)-8.4 (1.3)-7.7 (1.0)Tender joint count-5.3 (2.2)-6.6 (1.3)-6.4 (2.2)-11.3 (1.3)-11.5 (2.0)-11.6 (1.4)Physician’s Global Assessment of Disease Activity-20.6 (5.6)-20.6 (3.7)-29.1 (5.8)-32.6 (3.5)-30.1 (5.3)-32.1 (3.9)Patients’ Global Assessment of Disease Activity-14.9 (5.8)-13.4 (3.9)-23.0 (5.9)-28.4 (3.8)-28.2 (5.4)-24.9 (4.2)Pain-14.7 (5.6)-14.6 (3.9)-22.7 (5.7)-26.2 (3.7)-25.5 (5.3)-25.5 (4.2)HAQ-DI-0.23 (0.11)-0.04 (0.09)-0.31 (0.11)-0.38 (0.08)-0.48 (0.10)-0.34 (0.09)hsCRP12.0 (5.3)-4.4 (2.1)-10.1 (5.3)-13.3 (2.0)-4.9 (4.9)-10.0 (2.2)PASI total score2.5 (1.4)-2.3 (0.7)-3.7 (1.4)-4.0 (0.6)-4.0 (1.3)-4.9 (0.7)PASDAS-0.9 (0.4)-1.2 (0.3)-1.8 (0.4)-2.1 (0.2)-2.2 (0.3)-2.1 (0.3)The number of patients with data available for individual endpoints may vary.csDMARD, conventional synthetic disease-modifying antirheumatic drug; DEUC, deucravacitinib; HAQ-DI, Health Assessment Questionnaire-Disability Index; hsCRP, high-sensitivity C-reactive protein; PASDAS, Psoriatic Arthritis Disease Activity Score; PASI, Psoriasis Area and Severity Index; PBO, placebo; QD, once daily; SE, standard error; w, with; w/o, without.ConclusionThese analyses demonstrate that the efficacy of DEUC for the treatment of PsA was similar in pts with and without background csDMARD use. The AE profile of DEUC treatment with and without csDMARD use was consistent with findings from the overall Phase 2 PsA trial population.