Background: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 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 safety and efficacy were maintained through 4 years in the phase 3 moderate to severe plaque psoriasis POETYK PSO long-term extension (LTE) (NCT04036435) trial. The effect of deucravacitinib treatment on immune response to vaccines has not been evaluated.

Objectives: This POETYK PSO LTE substudy evaluated immune response to and safety of non-live pneumococcus (T-cell independent) and tetanus toxoid (T-cell dependent) vaccines in patients with plaque psoriasis receiving continuous deucravacitinib.

Methods: Patients were required to have received open-label deucravacitinib 6 mg once daily for ≥1 year in POETYK PSO LTE prior to the vaccine substudy. Patients were randomized 1:1 to blinded deucravacitinib or placebo on Day 1 through Day 36 to assess immune response to vaccination. Pre-vaccination serum titers, vaccinations, and safety assessments were performed on Day 8, vaccine-related safety assessments were performed remotely on Day 18, and post-vaccination titers and safety assessments were performed on Day 36. Primary endpoint was serologic response to 23-valent pneumococcal vaccine (PPSV-23) and tetanus toxoid vaccine (TTV) on Day 36. Secondary endpoints included seroprotection and seroconversion in tetanus toxoid-specific antibody titers, immune response measured by antibody titers and opsonophagocytic activity, and safety.

Results: Baseline patient demographics and clinical characteristics were similar across groups (deucravacitinib, n=28; placebo, n=25). Proportions of patients achieving serologic response criteria to PPSV-23 (deucravacitinib, 85.7% vs placebo, 100.0%; difference [95% CI], -14.3% [-31.5%, 1.6%]) and TTV (deucravacitinib, 64.3% vs placebo, 80.0%; -15.7% [-37.3%, 8.6%]) were high in the deucravacitinib group and numerically lower than in the placebo group. Tetanus toxoid seroprotection (100.0% vs 100.0%; 0.0% [-12.1%, 13.3%]) was achieved by all patients. Seroconversion (64.3% vs 76.0%; -11.7% [-34.0%, 12.8%]) was numerically lower with deucravacitinib versus placebo, respectively. After adjusting for baseline titers, PPSV-23 and TTV mean titers at Day 36 were generally similar across both treatment groups. Opsonophagocytic activity for pneumococcus serotypes was comparable in both groups at Day 36. Adverse events (AEs) were infrequent and comparable across groups; no severe or serious AEs were reported. No clinically meaningful changes in laboratory parameters related to study treatment were observed.

Conclusion: In patients with plaque psoriasis, continuing deucravacitinib treatment did not impact humoral immune responses to the PPSV-23 (T-cell independent) and TTV (T-cell dependent) vaccines. Our data suggest that withholding deucravacitinib treatment at the time of these vaccinations is not required.

REFERENCES: NIL.

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

Disclosure of Interests: Joanna Narbutt AbbVie, Amgen, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galderma, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi-Aventis/Genzyme, Sandoz, Takeda, and UCB, AbbVie, Amgen, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galderma, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi-Aventis/Genzyme, Sandoz, Takeda, and UCB, AbbVie, Amgen, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Galderma, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi-Aventis/Genzyme, Sandoz, Takeda, and UCB, Shahram Jacobs Bristol Myers Squibb, Kim Papp AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, DICE Therapeutics, Eli Lilly, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte Corporation, Janssen, Kymab, Kyowa Hakko Kirin, Leo Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB Pharma, and Zai Lab, AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, DICE Therapeutics, Eli Lilly, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte Corporation, Janssen, Kymab, Kyowa Hakko Kirin, Leo Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB Pharma, and Zai Lab, AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, DICE Therapeutics, Eli Lilly, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte Corporation, Janssen, Kymab, Kyowa Hakko Kirin, Leo Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB Pharma, and Zai Lab, Alessandra Alio Bristol Myers Squibb, Bristol Myers Squibb, Yi Luo Bristol Myers Squibb, Bristol Myers Squibb, Yanqiu Shao Bristol Myers Squibb, Bristol Myers Squibb, Victoria Berger Bristol Myers Squibb, Bristol Myers Squibb, Carolin Daamen Bristol Myers Squibb, Bristol Myers Squibb, Kevin L. Winthrop AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB; Research support: Bristol Myers Squibb and Pfizer.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.