Deucravacitinib in Plaque Psoriasis: Immune Response to and Safety of Pneumococcus and Tetanus Toxoid Vaccines in the POETYK LTE Trial

Abstract

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib safety and efficacy were maintained through 4 years in the phase 3 POETYK long-term extension (LTE) (NCT04036435) trial. The effect of deucravacitinib treatment on immune response to vaccines has not been evaluated. This POETYK LTE substudy evaluated immune response to and safety of non-live pneumococcus (T-cell independent) and tetanus toxoid (T-cell dependent) vaccines in patients receiving continuous deucravacitinib.

Methods: Patients were required to have received open-label deucravacitinib 6 mg once daily for ≥1 year in POETYK 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 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.