P77 Deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, vs. placebo and apremilast in moderate-to-severe plaque psoriasis: achievement of absolute Psoriasis Area and Severity Index thresholds in two phase III trials

Abstract

Abstract Deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, is approved in the USA and several other countries and is under review by the European Medicines Agency and other health authorities, for the treatment of moderate-to-severe plaque psoriasis. The efficacy and safety results for deucravacitinib in the phase III, 52-week, double-blind POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials in patients with moderate-to-severe plaque psoriasis have been published (Armstrong AW, Gooderham M, Warren RB et al. Deucravacitinib vs. placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial. J Am Acad Dermatol 2023; 88:29–39; Strober B, Thaçi D, Sofen H et al. Deucravacitinib vs. placebo and apremilast in moderate to severe plaque psoriasis: efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial. J Am Acad Dermatol 2023; 88:40–51). Additional efficacy outcomes using Psoriasis Area and Severity Index (PASI) measures were assessed. Patients were randomized 2 : 1 : 1 to oral deucravacitinib 6 mg once daily, placebo or apremilast 30 mg twice daily, with treatment switches at weeks 16 and 24 per study designs. Mean change from baseline PASI through to week 52, achievement of absolute PASI thresholds ≤ 3 and ≤ 4 at weeks 16 and 24 and proportions of patients treated continuously with deucravacitinib from day 1 who achieved absolute PASI thresholds ≤ 1, ≤ 2, ≤ 3, ≤ 4 and ≤ 5 at week 52 were determined. Mean baseline PASI was similar across groups in PSO-1 and PSO-2 (deucravacitinib, n = 332 and n = 511, respectively; placebo, n = 166 and n = 255; apremilast, n = 168 and n = 254). Mean change from baseline PASI (baseline mean 21.8) at peak efficacy at week 24 was −16.9 for PSO-1 patients treated continuously with deucravacitinib from day 1; decreases were maintained at week 52 (−17.1). At week 16, significantly higher proportions of deucravacitinib-treated patients vs. placebo and apremilast achieved absolute PASI thresholds ≤ 3 [PSO-1: 42.2%, 7.2% and 24.4%, respectively (P < 0.001 vs. placebo and apremilast); PSO-2: 40.9%, 6.7% and 29.5%, respectively (P < 0.001 vs. placebo and P = 0.002 vs. apremilast)] and ≤ 4 [PSO-1: 55.4%, 11.4% and 31.0%, respectively (P < 0.001 vs. placebo and apremilast); PSO-2: 49.5%, 9.4% and 37.4%, respectively (P < 0.001 vs. placebo and P = 0.001 vs. apremilast)]. Results were maintained for deucravacitinib vs. apremilast at week 24 (P < 0.001). Deucravacitinib patients treated continuously from day 1 achieved high rates of absolute PASI thresholds at week 52 in PSO-1 and PSO-2 (≤ 1, 31.3% and 23.4%, respectively; ≤ 2, 45.5% and 34.7%, respectively; ≤ 3, 54.5% and 44.0%, respectively; ≤ 4, 61.4% and 52.9%, respectively; ≤ 5, 66.0% and 59.5%, respectively). Patients with moderate-to-severe plaque psoriasis who received deucravacitinib achieved clinically meaningful absolute PASI outcomes superior to placebo and apremilast and showed good maintenance of these measures through to week 52. AcknowledgmentsWriting and editorial assistance was provided by Nick Cianciola PhD, CMPP, of Peloton Advantage, LLC, an OPEN Health company, funded by Bristol Myers Squibb. Funding sourcesThis study was sponsored by Bristol Myers Squibb.