Deucravacitinib in plaque psoriasis: 2-year safety and efficacy results from the phase III POETYK trials.

Background: In the phase III 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.
Objective: To evaluate deucravacitinib safety and efficacy over 2 years in patients participating in the phase III trials.
Methods: In the POETYK long-term extension (LTE), an ongoing phase IIIb 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 Psoriasis Area and Severity Index score (PASI 75) and static Physician's Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients originally randomized to deucravacitinib, patients who crossed over from placebo at week 16 and patients who achieved PASI 75 at week 24 (peak efficacy).
Results: At data cutoff (1 October 2021), 1519 patients had received at least one dose of deucravacitinib; 79.0% and 39.9% had ≥ 52 weeks and ≥ 104 weeks of total deucravacitinib exposure, respectively. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were similar at 1 year and 2 years for any AEs (229.2 vs. 154.4, respectively), 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) owing 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 haematological, chemistry or lipid parameters. Clinical responses were maintained in patients who received continuous deu-cravacitinib 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.
Conclusions: Deucravacitinib maintained efficacy and demonstrated consistent safety with no new safety signals observed through 2 years.
Competing Interests: Conflicts of interest M.L. has received research funds on behalf of Mount Sinai from: AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Ortho Dermatologics, Pfizer, Sanofi-Regeneron, and UCB, Inc., and is a consultant for Almirall, AltruBio Inc., AnaptysBio, Apogee, Arcutis, Inc., AstraZeneca, Atomwise, Avotres Therapeutics, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas, Dermavant Sciences, EPI, Evommune, Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Galderma, Genentech, Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Sanofi-Regeneron, Seanergy, Strata, Takeda, Trevi, and Verrica. R.B.W. has received research grants from AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer and UCB, and has received consulting fees from AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DICE Therapeutics, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, UCB and Union Therapeutics. H.S. has been a clinical investigator for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, LEO Pharma, Novartis and Sun Pharma. S.I. has received grants and personal fees from AbbVie, Eisai, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Sun Pharma, Taiho Yakuhin, Tanabe Mitsubishi and Torii Yakuhin, and has received personal fees from Amgen (Celgene), Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, and UCB. C.P. has received grants from and served as a consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Mylan, Novartis, Pfizer, Sandoz, and UCB. J.C.S. has served on an advisory board and served as a consultant for AbbVie, LEO Pharma, Novartis, Pierre-Fabre, Sanofi Genzyme, and Trevi; has served as a speaker for AbbVie, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis and Sanofi Genzyme; and has been an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InfraRX, Janssen-Cilag, Manlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Trevi, and UCB. L.S. has served as a consultant, paid investigator, and/or speaker for AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, LEO Pharma, Mayne Pharma, MedImmune, Merck, Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, Sun Pharma ANZ, Trius, UCB and Zai Lab. T.P. has served on an advisory board for and received consulting fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma and UCB. E.V., A.N., R.M.K. and S.B. are employees of and shareholders in Bristol Myers Squibb. A.B. is a consultant for Bristol Myers Squibb through functional service provider Cytel. D.T. has received research support from and has been a principal investigator (clinical trials) for AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Eli Lilly, Galderma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi and UCB; has served as a consultant for AbbVie, Almirall, Galapagos, LEO Pharma, Novartis, Pfizer, and UCB; has been a lecturer for AbbVie, Almirall, Amgen, Janssen, Eli Lilly, Leo Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Roche-Posay, Sandoz-Hexal, Sanofi, Target-Solution and UCB; and has served on a scientific advisory board for AbbVie, Amgen, Eli Lilly, Janssen-Cilag, LEO Pharma, Morphosis, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi and UCB. A.B. has served as a speaker (received honoraria) for AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, Regeneron and Sanofi; served as a scientific adviser (received honoraria) for AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Apogee, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, CTI BioPharma, Dermavant, EcoR1, Eli Lilly and Company, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO, Lipidio, Merck, Monte Rosa Therapeutics, Nektar, Novartis, Overtone Therapeutics, Pfizer, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB Pharma, Union, Ventyx, Vibliome and Xencor; and has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly and Company, Evelo, Evommune, Galderma, Incyte, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB Pharma and Ventyx.
(© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)