April W. Armstrong1, Mark Lebwohl2, Richard B. Warren3, Howard Sofen4, Shinichi Imafuku5, Mamitaro Ohtsuki6, Lynda Spelman7, Thierry Passeron8, Kim A Papp9, Renata M. Kisa10, Victoria Berger10, Eleni Vritzali11, Kim Hoyt10, Matthew J. Colombo10, Subhashis Banerjee10, Bruce Strober12, Diamant Thaçi13 and Andrew Blauvelt14, 1Keck School of Medicine of University of Southern California, Los Angeles, CA, 2Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, 3Dermatology Centre, Northern Care Alliance NHS Foundation Trust; NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom, 4University of California Los Angeles School of Medicine and Dermatology Research Associates, Los Angeles, CA, 5Fukuoka University Faculty of Medicine, Fukuoka, Japan, 6Jichi Medical University, Tochigi, Japan, 7Veracity Clinical Research, Brisbane, Australia, 8Université Côte d’Azur, University Hospital of Nice, Nice, France, 9Alliance Clinical Research and Probity Medical Research, Waterloo, and University of Toronto, Toronto, ON, Canada, 10Bristol Myers Squibb, Princeton, NJ, 11Bristol Myers Squibb, Sissach, Switzerland, 12Yale University, New Haven, CT, 13Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany, 14Oregon Medical Research Center, Portland, OR
Background/Purpose: Deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for the treatment of adults plaque psoriasis. Deucravacitinib was superior to placebo and apremilast in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials in plaque psoriasis and is currently being investigated in several immune-mediated diseases and has shown efficacy in phase 2 trials for SLE and PsA. Upon completion of the parent trials, patients could enroll in the POETYK long-term extension (LTE) trial (NCT04036435). In the present LTE analysis, we report safety and efficacy of deucravacitinib up to 3 years (week 148) through data cutoff (June 15, 2022).
Methods: PSO-1 and PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily (QD), or apremilast twice daily. At week 52, POETYK PSO-1 and PSO-2 patients enrolled in the LTE trial received open-label deucravacitinib 6 mg once daily. Safety was evaluated in patients who received ≥ 1 dose of deucravacitinib via exposure-adjusted incidence rate (EAIR) per 100 person-years (PY). Efficacy outcomes included ≥ 75%/≥ 90% reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician's Global Assessment (sPGA) score of 0 (clear) or 1 (almost clear) with a ≥ 2-point improvement from baseline. Efficacy was reported using modified nonresponder imputation (mNRI) in patients who received continuous deucravacitinib treatment from day 1 of the parent trial and were enrolled and treated in the LTE trial. As-observed results by treatment failure rule imputation were also analyzed.
Results: 1519 patients received ≥ 1 dose of deucravacitinib, with 513 patients receiving continuous deucravacitinib treatment from day 1 in PSO-1/PSO-2 and who were treated in the LTE trial. Cumulative exposure from parent trial randomization was 3294.3 PY for these safety analyses. EAIRs/100 PY were similar, or decreased, from the 2- to 3-year cumulative period, respectively, for adverse events (AEs) (154.4to 144.8), serious AEs (6.1 to 5.5), discontinuation due to AEs (2.8 to 2.4), herpes zoster (0.7 to 0.6), malignancies (0.9 to 0.9), major adverse cardiovascular events (0.4 to 0.3), venous thromboembolism (0.1 to 0.1), and deaths (0.4 to 0.3). Clinical response rates were maintained at week 148 by mNRI (PASI 75, 73.2% [95% CI, 68.7–77.8]; PASI 90, 48.1% [95% CI, 43.2–53.1]; sPGA 0/1, 54.1% [95% CI, 49.1–59.1]), with similar results regardless of data imputation methodology.
Conclusion: Deucravacitinib demonstrated a consistent safety profile through 3 years with no increases in AE or serious AE rates over time and no emergence of new or long-term safety signals. Efficacy was sustained through 3 years in patients treated continuously with deucravacitinib from day 1 in the parent trials. Since it is important to provide long-term safety for this new class of drugs, these findings provide additional support for deucravacitinib having a consistent safety profile and durable efficacy for up to 3 years of use in patients with plaque psoriasis.