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

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for 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 completing PSO-1/PSO-2. We report deucravacitinib safety and efficacy 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 QD, or apremilast 30 mg twice daily. At Week 52, patients enrolled in the LTE received open-label deucravacitinib 6 mg QD. Safety was evaluated in patients receiving ≥1 deucravacitinib dose using exposure-adjusted incidence rate per 100 person-years (EAIR/PY). Efficacy outcomes (PASI 75/90; sPGA 0/1) were analyzed using modified nonresponder imputation (mNRI) in patients receiving continuous deucravacitinib from Day 1 of the parent trial and treated in the LTE. Results: Of 1519 patients who received ≥1 deucravacitinib dose (3294.3 PY cumulative exposure), 513 received continuous deucravacitinib 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.