Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in Moderate to Severe Plaque Psoriasis: Efficacy by Baseline Body Surface Area (BSA) Involvement and Baseline Psoriasis Area and Severity Index (PASI)

Abstract

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 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. In the phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials, deucravacitinib was significantly more efficacious than placebo and apremilast. This analysis evaluated deucravacitinib efficacy by two measures of baseline disease severity, BSA involvement and PASI scores.

Methods: Patients were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily in both trials, which included 16-week placebo-controlled and 24-week apremilast-controlled periods from Day 1. Of patients randomized to deucravacitinib, those in PSO-1 were treated continuously for 52 weeks; in PSO-2, Week 24 PASI 75 responders were rerandomized to continued deucravacitinib or placebo. Patients randomized to placebo crossed over to deucravacitinib at Week 16 and were treated through Week 52. Efficacy outcomes, including ≥75%/≥90%/100% reductions from baseline in PASI (PASI 75/90/100) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1), were evaluated using nonresponder imputation in disease severity subgroups defined by baseline BSA involvement (10%-<15%, 15%-<20%, 20%-<30%, ≥30%) and PASI score (12-<15, ≥15). Results are reported through Week 24 in the pooled PSO-1/PSO-2 population (apremilast-controlled) and through Week 52 in the PSO-1 population (continuous deucravacitinib treatment).

Results: In the pooled PSO-1/PSO-2 population (N=1686), 391 (23.2%) had baseline BSA involvement of 10%-<15% (deucravacitinib, n=194), 371 (22.0%) had 15%-<20% (deucravacitinib, n=183), 391 (23.2%) had 20%-<30% (deucravacitinib, n=198), and 533 (31.6%) had ≥30% (deucravacitinib, n=268). For baseline PASI scores, 387 (23.0%) had a score of 12-<15 (deucravacitinib, n=183) and 1298 (77.0%) had a score of ≥15 (deucravacitinib, n=660). Deucravacitinib-treated patients had comparable PASI 75 response rates across all subgroups at Week 16 (BSA subgroups, 50.5%-58.2%; PASI subgroups, 48.6%-57.0%) and at Week 24 (BSA subgroups, 62.0%-64.1%; PASI subgroups, 59.9%-63.8%), with superior responses versus those in patients receiving placebo or apremilast evaluated in each subgroup. Similar findings were observed for all other efficacy measures. In PSO-1, efficacy was maintained through Week 52 with continuous deucravacitinib treatment across BSA (PASI 75, 67.1%-75.7%; sPGA 0/1, 52.1%-61.2%) and PASI subgroups (PASI 75, 65.6%-73.1%; sPGA 0/1, 54.7%-58.8%).

Conclusion: Deucravacitinib was efficacious in patients with moderate or severe plaque psoriasis regardless of extent of baseline BSA involvement or PASI scores.