Deucravacitinib 5-Year Safety and Efficacy Results in Plaque Psoriasis: A Phase 3 Open-Label Extension of Randomized Clinical Trials

Abstract

Background

Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis.

Objective

We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis.

Methods

PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years.

Results

Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a ≥ 75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2–76.1]; 5 years, 67.3% [62.0–72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1–61.9]; 5 years, 52.6% [47.0–58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0–57.1]) through 5 years (45.4% [40.0–50.8]).

Conclusions

These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib.

Clinical Trial Registration

NCT03624127, NCT03611751, NCT04036435.