Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase 3 poetyk trials

In the phase 3 POETYK PSO-1 and PSO-2 trials, deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, was well-tolerated and efficacious over 1 year in patients with psoriasis.Evaluate deucravacitinib safety and efficacy over 2 years in patients participating in the phase 3 trials.In the POETYK long-term extension (LTE), an ongoing, phase 3b, open-label trial, adults with moderate to severe plaque psoriasis who completed PSO-1 or PSO-2 receive deucravacitinib 6 mg once daily. Safety was assessed via adverse events (AEs) and laboratory parameter abnormalities. Efficacy endpoints, including ≥75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients originally randomized to deucravacitinib, patients crossing over from placebo at Week 16, and patients achieving PASI 75 at Week 24 (peak efficacy).At data cutoff (October 1, 2021), 1519 patients had received ≥1 dose of deucravacitinib; 79.0% and 39.9% had ≥52 weeks and ≥104 weeks, respectively, of total deucravacitinib exposure. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were similar at 1 year and 2 years, respectively, for any AEs (229.2 vs 154.4), serious AEs (5.7 vs 6.1), discontinuations (4.4 vs 2.8), deaths (0.2 vs 0.4), serious infections (1.7 vs 2.6), herpes zoster (0.9 vs 0.8), major adverse cardiovascular events (0.3 vs 0.4), venous thromboembolic events (0.2 vs 0.1), and malignancies (1.0 vs 0.9). EAIRs for COVID-19 infections were higher at 2 years than at 1 year (5.1 vs 0.5) due to the peak of the global COVID-19 pandemic occurring during the LTE. No clinically meaningful changes from baseline or trends were observed over 2 years in haematologic, chemistry, or lipid parameters. Clinical responses were maintained in patients receiving continuous deucravacitinib treatment from baseline (PASI 75: Week 52, 72.4%; Week 112, 79.7%; sPGA 0/1: Week 52, 57.9%; Week 112, 61.1% [as observed]). Responses at Week 52 were also maintained in placebo crossovers and in Week 24 PASI 75 responders.Deucravacitinib maintained efficacy and demonstrated consistent safety with no new safety signals observed through 2 years. (ClinicalTrials.gov identifier: NCT04036435).