P096 Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in moderate-to-severe plaque psoriasis: safety profile in older (≥ 65 years) and younger (&amp;lt; 65 years) patients in the phase III POETYK PSO-1, PSO-2 and long-term extension trials
Authors: Niamh Kearney, Andrew Pink, Kim Hoyt, Renata M Kisa, Subhashis Banerjee, Alexandra Rogers, Jill Mullan, Richard B Warren
Journal: British Journal of Dermatology (2024)

Abstract Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is approved in the USA, EU, UK 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 III POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) trials in moderate-to-severe plaque psoriasis. It also maintained efficacy through 3 years with no new safety signals in the POETYK long-term extension (LTE) (NCT04036435) trial. Older patients (≥ 65 years) typically have more comorbidities and may have increased risk of adverse events (AEs). Many clinical studies of novel psoriasis agents excluded older patients, limiting the generalizability of reported safety profiles. This post hoc analysis evaluated the safety profile of deucravacitinib in older (≥ 65 years) and younger (&amp;lt; 65 years) patients through 3 years in the POETYK trials. POETYK PSO-1 and PSO-2 randomized eligible patients 1 : 2 : 1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At week 52, patients could enrol in the LTE and receive open-label deucravacitinib. Safety was evaluated through 3 years in patients originally randomized to placebo or deucravacitinib (data cutoff 15 June 2022) using two key AE outcomes, serious AEs (SAEs) and discontinuation due to AEs (DcAEs), based on baseline age (≥ 65 years and &amp;lt; 65 years). Outcomes were expressed as exposure-adjusted incidence rates per 100 person-years (EAIR/100 PY) in patients who received at least one dose of deucravacitinib. There were fewer patients aged ≥ 65 years than &amp;lt; 65 years in the placebo (n = 79 and n = 587, respectively) and deucravacitinib (n = 133 and n = 1231) treatment groups. EAIRs/100 PY for SAEs over weeks 0–52 were higher in patients aged ≥ 65 years compared with patients aged &amp;lt; 65 years receiving placebo (10.2 and 5.0, respectively) or deucravacitinib (14.6 and 4.8). For DcAEs, EAIRs/100 PY were 10.1 and 9.2, respectively, with placebo, and 11.9 and 3.6 with deucravacitinib. Incidence rates in each age group remained consistent or decreased through 3 years in the LTE trial with continued deucravacitinib treatment (SAEs: ≥ 65 years, 10.3; &amp;lt; 65 years, 5.0; DcAEs: ≥ 65 years, 5.1; &amp;lt; 65 years, 2.1). Deucravacitinib maintained a consistent safety profile through 3 years of exposure for both older and younger patients. As expected, AEs were higher in older vs. younger patients in both treatment groups. Rates of SAEs and DcAEs with deucravacitinib were comparable with placebo in both age groups in year 1 and were similar or trended down with long-term deucravacitinib treatment through 3 years. Conflicts of interest: N.K. has received speaker fees from Janssen and UCB, and honoraria from AbbVie, Janssen, Eli Lilly, Novartis and UCB. A.P. has received investigator, speaker or advisor fees, educational support and research grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi and UCB. K.H. is a consultant for Bristol Myers Squibb via Syneos Health. R.M.K., S.B., A.R. and J.M. are employees and shareholders of Bristol Myers Squibb. R.B.W. has received research grants from AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer and UCB; and consulting fees from AbbVie, Almirall, Amgen, Astellas, Boehringer Ingelheim, Celgene, Dice Therapeutics, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, UCB and UNION Therapeutics.