POS1046 DEUCRAVACITINIB LONG-TERM EFFICACY AND SAFETY IN PLAQUE PSORIASIS: 2-YEAR RESULTS FROM THE PHASE 3 POETYK PSO PROGRAM

Abstract

BackgroundTyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signalling of key cytokines (eg, interleukin [IL]-23 and Type I interferons) involved in the pathogenesis of immune-mediated diseases including plaque psoriasis and psoriatic arthritis (PsA). Deucravacitinib is a novel, oral, selective TYK2 inhibitor that achieves high selectivity by uniquely binding to the regulatory domain of the enzyme, rather than to the more conserved active domain. Deucravacitinib showed superior efficacy compared with placebo at 16 weeks in a Phase 2 trial in patients with PsA.1 The efficacy and tolerability of deucravacitinib in patients with moderate to severe psoriasis were previously demonstrated in 2 pivotal, Phase 3, double-blind trials, POETYK PSO-1 and PSO-2.2ObjectivesTo assess the long-term efficacy and safety of deucravacitinib in patients with psoriasis in a Phase 3, open-label, long-term extension (LTE) trial.MethodsThe 52-week PSO-1 and PSO-2 trials randomised patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients could then enrol in the LTE trial and receive open-label deucravacitinib 6 mg once daily.Results1221 patients enrolled in the LTE trial and received ≥1 dose of deucravacitinib. Demographic and baseline disease characteristics were balanced across treatment groups; mean age at disease onset was 28.6 years, mean disease duration was 18.9 years, and 18.0% of patients had PsA at baseline. Cumulative exposures in person-years from randomisation in PSO-1 or PSO-2 and the LTE trial were 2166.9 and 2482.0 for efficacy and safety analyses, respectively. At enrolment in the LTE trial, PASI 75 and sPGA 0/1 response rates were 65.1% and 50.9%, respectively, and were maintained for up to 2 years after initial randomisation (Week 48 of LTE; PASI 75: 75.7%; sPGA 0/1: 56.4% [as observed]). Exposure-adjusted incidence rates per 100 person-years for adverse events were similar in the controlled period (Weeks 0–52) of PSO-1 and PSO-2 and during the cumulative PSO-1, PSO-2, and LTE trial period (229.2 [controlled period] vs 154.4 [cumulative period]), serious adverse events (5.7 vs 6.1), discontinuations (4.4 vs 2.8), deaths (0.2 vs 0.4), herpes zoster (0.9 vs 0.7), malignancies (1.0 vs 0.9), major adverse cardiovascular events (0.3 vs 0.4), and venous thromboembolism (0.1 vs 0.1).ConclusionDeucravacitinib demonstrated persistent efficacy and consistent safety profiles in patients with psoriasis for up to 2 years after initial randomisation in the POETYK PSO-1, PSO-2, and LTE trials.