Background: Oral, targeted therapies for plaque psoriasis with long-term efficacy and safety are needed. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib is also in development for treatment of psoriatic arthritis (phase 3), Sjögren’s syndrome (phase 3), systemic lupus erythematosus (phase 3), and discoid lupus erythematosus (phase 2). Deucravacitinib was efficacious and well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials.

Objectives: We report deucravacitinib safety and efficacy through 5 years (Week 256; cutoff date, September 2, 2024).

Methods: Patients were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. After Week 52, patients enrolled in the POETYK PSO long-term extension (LTE) (NCT04036435) trial received open-label deucravacitinib 6 mg once daily. Safety was evaluated in patients (n=1519) receiving ≥1 deucravacitinib dose through 5 years in the POETYK PSO-1, PSO-2, or LTE trials. Exposure-adjusted incidence rate per 100 person-years was used to assess adverse events. Efficacy was analyzed using modified nonresponder imputation in patients who received continuous deucravacitinib from Day 1 of the parent trials and were enrolled and treated in the LTE. Outcomes included ≥75%/≥90% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75/90), and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1).

Results: Deucravacitinib was well tolerated with no new safety signals. In patients receiving continuous deucravacitinib as described above (n=513), high clinical response rates were generally maintained from Year 1 (PASI 75, 72.1% [95% CI, 68.2%-76.1%]; PASI 90, 45.9% [95% CI, 41.5%-50.4%]; sPGA 0/1, 57.5% [95% CI, 53.1%-61.9%]) to Year 5 (PASI 75, 67.3% [95% CI, 62.0%-72.6%]; PASI 90, 46.3% [95% CI, 41.2%-51.5%]; sPGA 0/1, 52.6% [95% CI, 47.0%-58.1%]).

Conclusion: Deucravacitinib demonstrated a consistent safety profile through 5 years with no emergence of any new safety signals. Clinical efficacy rates were maintained through 5 years of continuous treatment with once-daily oral deucravacitinib. These data support the long-term safety and durable efficacy profile through 5 years of treatment with deucravacitinib, a first-in-class TYK2 inhibitor treatment for psoriasis.

REFERENCES: NIL.

Acknowledgements: This study was sponsored by Bristol Myers Squibb. Writing and editorial assistance was provided by Kimberly MacKenzie, PhD, of Peloton Advantage, LLC, an OPEN Health company, funded by Bristol Myers Squibb.

Disclosure of Interests: April W. Armstrong AbbVie, Almirall, Arcutis, Aslan, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, EPI Health, Incyte, Janssen, Leo Pharma, Mindera Health, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB, AbbVie, Almirall, Arcutis, Aslan, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Eli Lilly, EPI Health, Incyte, Janssen, Leo Pharma, Mindera Health, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB, Richard B. Warren AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Astellas, Boehringer Ingelheim, Celgene, DICE Therapeutics, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Union Therapeutics, Bruce Strober AbbVie, Arcutis, Dermavant, Eli Lilly, Incyte, Janssen/J&J Innovative Medicine, Regeneron, and Sanofi, Connect Biopharma and Mindera Health, AbbVie, Acelyrin, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Celltrion, CorEvitas Psoriasis Registry, Dermavant, Eli Lilly, Inmagene, Janssen/J&J Innovative Medicine, Kangpu Biopharmaceuticals, Leo Pharma, Maruho, Meiji Seika Pharma, Monte Rosa Therapeutics, Novartis, Pfizer, Protagonist, RAPT Therapeutics, Regeneron, Sanofi, Sun Pharma, Takeda, TD Cowen, UCB, Union Therapeutics, Ventyx Biosciences, and vTv Therapeutics, CorEvitas Psoriasis Registry, Andy Blauvelt Speaker (with honoraria): Lilly and UCB; Scientific adviser (with honoraria): AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Apogee, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Celldex, CTI BioPharma, Dermavant, EcoR1, Eli Lilly, Escient, Evelo Biosciences, Evommune, Forte Biosciences, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo Pharma, Lipidio, Microbion, Merck, Monte Rosa Therapeutics, Nektar, Novartis, Overtone Therapeutics, Paragon, Pfizer, Q32 Bio, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB, Union Therapeutics, Ventyx Biosciences, Vibliome, and Xencor, Lipidio and Oruka, AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, DermBiont, Eli Lilly, Evelo Biosciences, Evommune, Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, Takeda, UCB Pharma, and Ventyx Biosciences, Yayoi Tada AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Maruho, Novartis, Taiho, and UCB, AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Eli Lilly, Jimro, Kyowa Kirin, Leo Pharma, Maruho, Sun Pharma, Taiho Pharmaceutical, Tanabe-Mitsubishi, Torii, and UCB; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Eli Lilly, Janssen, Jimro, Kyowa Kirin, Leo Pharma, Maruho, Novartis, Pfizer, Sun Pharma, Taiho, Tanabe-Mitsubishi, Torii, and UCB, Thierry Passeron AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, Takeda, and UCB, Diamant Thaçi AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Sanofi, and UCB, AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Leo Pharma, Novartis, Pfizer, and UCB; Lecturer: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Roche-Posay, Sanofi, Target RWE, and UCB, AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi, and UCB, Carolin Daamen Bristol Myers Squibb, Bristol Myers Squibb, Janice Li Bristol Myers Squibb, Bristol Myers Squibb, Zoran Popmihajlov Bristol Myers Squibb, Bristol Myers Squibb, John Vaile Bristol Myers Squibb, Bristol Myers Squibb, Julie Scotto Bristol Myers Squibb, Bristol Myers Squibb, Mark Lebwohl Almirall, AltruBio, AnaptysBio, Arcutis, Avotres, Boehringer Ingelheim, Brickell Biotech, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas Psoriasis Registry, Dermavant, EPI Health, Evommune, Forte Biosciences, Galderma, Genentech, Incyte, Leo Pharma, Meiji Seika Pharma, Mindera Health, Pfizer, Seanergy, Strata, Trevi, and Verrica, AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Eli Lilly, Incyte, Janssen, Ortho Dermatologics, Regeneron, and UCB.

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