Deucravacitinib in Moderate to Severe Plaque Psoriasis: 5-year, Long-term Safety and Efficacy Results from the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

Introduction: Oral, targeted therapies for plaque psoriasis with long-term efficacy and safety are needed. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious and well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials. Here, we report deucravacitinib safety and efficacy through 5 years (Week 256; cutoff date, 9/2/2024). Methods: Patients were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. After Week 52, patients enrolled in the POETYK long-term extension (LTE) (NCT04036435) trial received open-label deucravacitinib 6 mg once daily. Safety was evaluated in patients (n=1519) receiving ≥1 deucravacitinib dose through 5 years in the POETYK PSO-1, PSO-2, or LTE trials. Exposure-adjusted incidence rate per 100 person-years was used to assess adverse events. Efficacy was analyzed using modified nonresponder imputation in patients who received continuous deucravacitinib from Day 1 of the parent trials and were enrolled and treated in the LTE. Outcomes included PASI 75/90 and sPGA 0/1. Results: Deucravacitinib was well tolerated with no new safety signals. In patients receiving continuous deucravacitinib as described above (n=513), high clinical response rates were generally maintained from Year 1 (PASI 75, 72.1% [95% CI, 68.2%-76.1%]; PASI 90, 45.9% [95% CI, 41.5%-50.4%]; sPGA 0/1, 57.5% [95% CI, 53.1%-61.9%]) to Year 5 (PASI 75, 67.3% [95% CI, 62.0%-72.6%]; PASI 90, 46.3% [95% CI, 41.2%-51.5%]; sPGA 0/1, 52.6% [95% CI, 47.0%-58.1%]). Conclusion: Deucravacitinib demonstrated a consistent safety profile through 5 years with no emergence of any new safety signals. Clinical efficacy rates were maintained through 5 years of continuous treatment with once-daily oral deucravacitinib. These data support the long-term safety and durable efficacy profile through 5 years of treatment with deucravacitinib, a first-in-class TYK2 inhibitor treatment for psoriasis.