P114 Deucravacitinib treatment did not affect immune response to SARS-Cov-2 vaccines and infection in patients with plaque psoriasis: results from the Phase 3 POETYK long-term extension trial

Abstract Introduction Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious and well tolerated in the global, 52-week, Phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) trials. Patients completing the parent trials could enrol in the ongoing, open-label POETYK long-term extension (LTE) (NCT04036435), which overlapped with the peak of the global COVID-19 (SARS-CoV-2) pandemic. We investigated serological responses and predictors of seroconversion to SARS-CoV-2 vaccination and/or infection during deucravacitinib treatment in the POETYK LTE. Methods POETYK LTE started in August 2019 and overlapped with the COVID-19 pandemic, which emerged in December 2019. The first infection in the POETYK program was reported 24 March 2020, the first vaccination occurred on 17 December 2020, and samples were collected through 2 August 2023. This analysis included patients who (i) were fully vaccinated with an mRNA vaccine or a non-mRNA vaccine or had a reported SARS-CoV-2 infection during the trial and (ii) had their first serum sample available ≥15 days after the second mRNA dose or ≥30 days and up to 229 days after a non-mRNA vaccine or infection. Spike RBD antibody level ≥0.8 U/mL and nucleocapsid antibody level ≥1.0 cut-off index were used as measures of seroconversion; nucleocapsid antibody levels ≥1.0 U/mL were used as an indicator of prior SARS-CoV-2 infection. Results 596 (87.8%) patients were vaccinated (mRNA vaccine, n = 498; non-mRNA vaccine, n = 98). Baseline characteristics were similar between patients who were vaccinated (n = 406), infected (n = 83), and both vaccinated and infected (n = 190). Seroconversion occurred in 99.2% of mRNA vaccine recipients and 98.9% of non-mRNA vaccine recipients [mean RBD antibody levels, 9085.1 and 4277.9 U/mL, respectively; range, 0.4–75 000 U/mL (seroconversion, ≥0.8 U/mL titre)]. Seroconversion occurred in 100% of infected unvaccinated patients (mean RBD antibody level, 3663.8 U/mL), 99.1% of noninfected vaccinated patients (6384.2 U/mL), and 100% of infected vaccinated patients (23 636.2 U/mL). The mean duration between reported infection and sample collection was 177 days. RBD antibody levels remained high for >24 weeks in mRNA vaccine recipients, regardless of the time after vaccination or infection. Age, body mass index, and sex were not predictors of antibody levels or seroconversion. Conclusions In the POETYK LTE trial, >98% of patients mounted a serologic response to SARS-CoV-2 vaccination and/or infection, with more robust responses in vaccinated than unvaccinated patients. Deucravacitinib did not impact immune responses to vaccines that protect against COVID-19.