Deucravacitinib in Plaque Psoriasis: 3-Year Safety and Efficacy Results From the Phase 3 POETYK PSO-1 and PSO-2 Trials

Abstract

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in the POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) parent trials in moderate to severe plaque psoriasis. The POETYK long-term extension (LTE; NCT04036435) trial enrolled patients who completed PSO-1/PSO-2. We report safety and efficacy of deucravacitinib for up to 3 years (Week 148; through cutoff 6/15/2022). Methods: PSO-1/PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily (QD), or apremilast twice daily. At Week 52, patients enrolled in the LTE received open-label deucravacitinib 6 mg QD. Safety was evaluated in patients who received ≥1 dose of deucravacitinib using exposure-adjusted incidence rate per 100 person-years (EAIR/PY). Efficacy outcomes (≥75%/≥90% reduction from baseline in Psoriasis Area and Severity Index [PASI 75/90]; static Physician Global Assessment score of 0 [clear] or 1 [almost clear] with a ≥2-point improvement from baseline [sPGA 0/1]) were analyzed using modified nonresponder imputation (mNRI) in patients who received continuous deucravacitinib treatment from Day 1 of the parent trial and were treated in the LTE. Results: Of 1519 patients who received ≥1 dose of deucravacitinib (3294.3 PY cumulative exposure), 513 patients received continuous deucravacitinib treatment from Day 1 in PSO-1/PSO-2 and were treated in the LTE. EAIRs/100 PY were comparable, or decreased, between the 2-year and 3-year cumulative periods, respectively, for AEs (154.4, 144.8), serious AEs (6.1, 5.5), discontinuations due to AEs (2.8, 2.4), herpes zoster (0.7, 0.6), malignancies (0.9, 0.9), major adverse cardiovascular events (0.4, 0.3), venous thromboembolism (0.1, 0.1), and deaths (0.4, 0.3). Response rates were maintained at Week 148 by mNRI (PASI 75, 73.2%; PASI 90, 48.1%; sPGA 0/1, 54.1%). Conclusion: Deucravacitinib maintained a consistent safety profile and durable efficacy for up to 3 years.