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Clinical Trial
. 2025 Jul;39(7):1336-1351.
doi: 10.1111/jdv.20553. Epub 2025 Mar 6.

Deucravacitinib in plaque psoriasis: Four-year safety and efficacy results from the Phase 3 POETYK PSO-1, PSO-2 and long-term extension trials

April W Armstrong  1 , Mark Lebwohl  2 , Richard B Warren  3   4 , Howard Sofen  1   5 , Akimichi Morita  6 , Carle Paul  7 , Kim A Papp  8 , Matthew J Colombo  9 , Julie Scotto  9 , John Vaile  9 , Joe Zhuo  9 , Eleni Vritzali  9 , Victoria Berger  9 , Georgene Schroeder  9 , Subhashis Banerjee  9 , Diamant Thaçi  10 , Bruce Strober  11
Affiliations
Clinical Trial

Deucravacitinib in plaque psoriasis: Four-year safety and efficacy results from the Phase 3 POETYK PSO-1, PSO-2 and long-term extension trials

April W Armstrong et al. J Eur Acad Dermatol Venereol. 2025 Jul.

Abstract

Background: 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.

Objectives: To evaluate the safety and efficacy of deucravacitinib through 4 years in the Phase 3 POETYK PSO-1, PSO-2 and long-term extension (LTE) trials in psoriasis.

Methods: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily (QD) or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib 6 mg QD. Safety was evaluated in patients who received ≥1 dose of deucravacitinib at any time. Clinical and patient-reported outcomes (PASI, PGA and DLQI) were analysed in patients who received continuous deucravacitinib from Day 1 of the parent trials and enrolled in the LTE trial.

Results: In total, 1519 patients received ≥1 dose of deucravacitinib, with cumulative exposure of 4392.8 person-years (PY) through the data cut-off of 1 November 2023. Exposure-adjusted incidence rates (EAIRs)/100 PY of noted safety measures were comparable or decreased from the 1-year to 4-year cumulative period, respectively, for adverse events (AEs) (229.23, 131.68), serious AEs (including COVID-19) (5.68, 5.01), deaths (0.20, 0.25), discontinuation due to AEs (4.38, 2.20), herpes zoster (0.81, 0.55), malignancies (1.02, 0.89), major adverse cardiovascular events (0.30, 0.32) and venous thromboembolism (0.20, 0.07). In patients who received continuous deucravacitinib (n = 513), clinical and patient-reported outcome rates were well maintained from 1 year through 4 years (e.g. PASI 90, 1 year, 45.6% [95% CI, 41.3%-50.0%], 4 years, 47.5% [42.6%-52.4%]; DLQI 0/1, 1 year, 51.5% [47.1%-55.9%], 4 years, 49.4% [44.4%-54.4%]).

Conclusions: Deucravacitinib demonstrated a consistent safety profile and durable efficacy through 4 years of treatment in patients with moderate to severe plaque psoriasis.

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Conflict of interest statement

Dr. Armstrong has served as a research investigator, scientific advisor and/or speaker for AbbVie, Almirall, Arcutis, Aslan, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, EPI Health, Incyte, Janssen, Leo Pharma, Lilly, Mindera Health, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma and UCB. Dr. Lebwohl has received research funds on behalf of Mount Sinai from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Incyte, Janssen, Lilly, Ortho Dermatologics, Regeneron and UCB, and has served as a consultant for 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. Dr. Warren has received research grants from AbbVie, Almirall, Amgen, Celgene, Janssen, Leo Pharma, Lilly, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Almirall, Amgen, Astellas, Boehringer Ingelheim, Celgene, Dice Therapeutics, GSK, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi, UCB and Union Therapeutics. Dr. Sofen has served as a clinical investigator for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Lilly, Novartis and Sun Pharma. Dr. Morita has received honoraria as meeting chair/lecturer for AbbVie, AYUMI Pharmaceutical, Boehringer Ingelheim Japan, Celgene K.K., Eisai, Eli Lilly Japan K.K., Inforward, Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho Co., Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis Pharma K.K., Taiho Pharmaceutical, Torii Pharmaceutical and Ushio; has received funding from AbbVie G.K., Eisai, Eli Lilly Japan K.K., Kyowa Hakko Kirin, Leo Pharma K.K., Maruho, Mitsubishi Tanabe Pharma, Novartis Pharma K.K., Taiho Pharmaceutical and Torii Pharmaceutical; and has received consulting fees from AbbVie GK, Boehringer Ingelheim Japan, Bristol Myers Squibb, Celgene K.K., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho, Mitsubishi Tanabe Pharma, Nichi‐Iko Pharmaceutical, Nippon Kayaku, Novartis Pharma K.K., Pfizer Japan, Sun Pharma, Torii Pharmaceutical and UCB Japan. Dr. Paul has received grants and served as consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Merck, Mylan, Novartis, Pfizer, Sandoz and UCB. Dr. Papp has received honoraria and/or grants from AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can‐Fite Biopharma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, Dice Pharmaceuticals, Dice Therapeutics, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte, Janssen, Kymab, Kyowa Hakko Kirin, Leo Pharma, Lilly, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, Sanofi‐Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB and Zai Lab. Dr. Colombo, Ms. Scotto, Dr. Vaile, Dr. Zhou, Dr. Vritzali and Dr. Berger are employees of and stockholders in Bristol Myers Squibb. Ms. Schroeder is a consultant for Bristol Myers Squibb via Syneos Health. Dr. Banerjee was an employee of and stockholder in Bristol Myers Squibb at the time of the study. Dr. Thaçi has received research support from and a principal investigator (clinical trial funds to institution) for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Janssen‐Cilag, Leo Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi and UCB; has served as a consultant for AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Leo Pharma, Novartis, Pfizer and UCB; has served as a lecturer for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Roche‐Posay, Sanofi, Target RWE and UCB; and has served on a scientific advisory board for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen‐Cilag, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi and UCB. Dr. Strober has served as a consultant with honoraria for AbbVie, Acelyrin, Alamar, Almirall, Alumis, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Capital One, Celltrion, CorEvitas Psoriasis Registry, Dermavant, Imagenebio, Janssen/J&J Innovative Medicine, Kangpu Biopharmaceuticals, Leo Pharma, Lilly, Maruho, Meiji Seika Pharma, Monte Carlo, Novartis, Pfizer, Protagonist, Rapt Therapeutics, Regeneron, Sanofi, SG Cohen, Sun Pharma, Takeda, UCB, Union Therapeutics, Ventyx Biosciences and vTv Therapeutics; has served as a speaker for AbbVie, Arcutis, Dermavant, Incyte, Janssen/J&J Innovative Medicine, Lilly, Regeneron and Sanofi; has served a co‐scientific director (with consulting fee) and investigator for CorEvitas Psoriasis Registry; has served the editor‐in‐chief with an honorarium for Journal of Psoriasis and Psoriatic Arthritis; and has stock options in Connect Biopharma and Mindera Health.

Figures

FIGURE 1
FIGURE 1
The POETYK PSO‐1, PSO‐2 and LTE study designs. a Apremilast was titrated from 10 mg QD to 30 mg BID over the first 5 days of dosing. b Upon relapse (≥50% loss of Week 24 PASI percentage improvement from baseline), patients were to be switched to deucravacitinib 6 mg QD; due to a programming error, however, these patients continued on placebo until Week 52. c Data reported through the 208‐day POETYK LTE cut‐off date of 1 November 2023. Reproduced with permission from Lebwohl M, et al. BID, twice daily; LTE, long‐term extension; PASI 50/75, ≥50%/≥75% reduction from baseline in Psoriasis Area and Severity Index; QD, once daily.
FIGURE 2
FIGURE 2
Changes in haematology, chemistry and lipid parameters (a‐l) over 4 years in patients receiving deucravacitinib. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPK, creatine phosphokinase; LLN, lower limit of normal; LTE, long‐term extension; SD, standard deviation; ULN, upper limit of normal.
FIGURE 3
FIGURE 3
Clinical efficacy outcomes through 4 years. (a) PASI 75. (b) PASI 90. (c) PASI 100. (d) sPGA 0/1. (e) sPGA 0. Data callouts represent response rate (95% CI). CI, confidence interval; LTE, long‐term extension; mNRI, modified nonresponder imputation; PASI 75/90/100, ≥75%/≥90%/100% reduction from baseline in Psoriasis Area and Severity Index; sPGA 0/1, static Physician Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥ 2‐ point improvement from baseline; TFR, treatment failure rules.
FIGURE 4
FIGURE 4
Adjusted mean per cent change from baseline in PASI score through 4 years with MI‐BOCF imputation. Data callouts represent mean percent change from baseline (95% CI). CI, confidence interval; LTE, long‐term extension; MI‐BOCF, baseline observation carried forward with multiple imputation; PASI, Psoriasis Area and Severity Index; SD, standard deviation.
FIGURE 5
FIGURE 5
(a) ss‐PGA 0/1 and (b) PGA‐F 0/1 response rates with continuous deucravacitinib treatment from Day 1–4 years. Data callouts represent the response rate (95% CI). CI, confidence interval; LTE, long‐term extension; mNRI, modified nonresponder imputation; PGA‐F, Physician Global Assessment‐Fingernail; ss‐PGA, scalp‐specific Physician Global Assessment; TFR, treatment failure rules.
FIGURE 6
FIGURE 6
PSSD total score change from baseline with continuous deucravacitinib treatment through 4 years. Data from Weeks 0–52 reflect the weekly average of daily scores using the 24‐hour recall PSSD. Weeks 68–196 reflect the 7‐day recall PSSD score. Patient‐reported outcomes were recorded on a different schedule than clinical efficacy and safety outcomes; therefore, they are reported through Week 196 (the closest timepoint to Week 208). Data callouts represent mean score change from baseline (95% CI). CI, confidence interval; LTE, long‐term extension; MI‐BOCF, baseline observation carried forward with multiple imputation; PSSD, Psoriasis Symptoms and Signs Diary; SD, standard deviation.
FIGURE 7
FIGURE 7
DLQI 0/1 response rate with continuous deucravacitinib treatment through 4 years in patients with parent study baseline DLQI ≥2. Patient‐reported outcomes were recorded on a different schedule than clinical efficacy and safety outcomes; therefore, they are reported through Week 196 (the closest timepoint to Week 208). Data callouts represent response rate (95% CI). CI, confidence interval; DLQI 0/1, Dermatology Life Quality Index of 0 or 1; LTE, long‐term extension; mNRI, modified nonresponder imputation.
FIGURE 8
FIGURE 8
Incidence rates of AEs of interest (a‐c), deucravacitinib versus other systemic psoriasis treatments. The deucravacitinib data represent the phase 3 safety pool through the LTE cut‐off date of 01 November 2023. Published data on malignancies excluding NMSC were not available for secukinumab. Incidence rates for patients with psoriasis stratified by therapy are from the Optum Claims Analysis; data on file [Bristol Myers Squibb, 2024]. BADBIR, British Association of Dermatologists Biologic and Immunomodulators Register; CI, confidence interval; EAIR, exposure‐adjusted incidence rate; IL, interleukin; LTE, long‐term extension; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PsoBest, the German Psoriasis Registry; PSOLAR, the Psoriasis Longitudinal Assessment and Registry; PY, person‐years; SEER, Surveillance, Epidemiology, and End Results programme; TNF, tumour necrosis factor.
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