A Phase 4 Multicenter, Randomized, Open-Label, Efficacy Assessor-Blinded Study of Risankizumab Compared With Deucravacitinib for the Treatment of Adult Patients With Moderate Plaque Psoriasis Who Are Candidates for Systemic Therapy: 16-Week Results From IMMpactful

Abstract

Introduction Psoriasis (PsO) is a chronic immune-mediated disease that presents as thick and scaly skin plaques. Several biologics and oral treatments are available for the treatment of PsO, but variations across efficacy, safety, and treatment endpoints can make treatment optimization challenging for physicians in the absence of head-to-head comparisons. Risankizumab (RZB), an IL-23 inhibitor, and deucravacitinib (DEU), a tyrosine kinase 2 inhibitor, are both approved for the treatment of moderate-to-severe PsO. This study is evaluating the safety and efficacy of RZB vs DEU for the treatment of patients with moderate PsO without prior biologic treatment.

Methods IMMpactful is a phase 4 (NCT06333860), global, multicenter, randomized, open-label, efficacy assessor-blinded, active comparator study examining the effect of RZB vs DEU in adult patients with moderate PsO. Patients (≥ 18 years) eligible for systemic treatment with no prior biologic exposure, with body surface area 10%-≤15%, psoriasis area and severity index (PASI) ≥ 12, and static physician global assessment (sPGA) of 3 (moderate) were enrolled. The 52-week treatment period was split into 2 periods. In period A (weeks 0–16), patients were randomized (1:2) to subcutaneous (SC) injection of RZB 150 mg on Day 1 and Week 4 or oral DEU 6 mg daily (QD), respectively. In period B (weeks 16–52), patients continued RZB every 12 weeks, and patients initially randomized to DEU were re-randomized 1:1 to RZB 150 mg SC or oral DEU 6 mg QD and stratified by PASI 90 response (nonresponder, responder). In period A, the coprimary endpoints were achievement of ≥ 90% improvement in PASI (PASI 90) and achievement of sPGA 0 or 1 (sPGA 0/1) with at least a 2-grade improvement from baseline. Ranked secondary endpoints for period A included the achievement of PASI 100, and sPGA 0 with at least a 2-grade improvement from baseline at Week 16. Results from period A are presented.  Nonresponder imputation incorporating multiple imputations was used to handle missing data.

Results Of the 393 enrolled patients, 131 (mean age [SD]: 47.3 [14.1] years) were randomized to RZB, and 262 (mean age [SD]: 44.8 [13.8] years) were randomized to DEU. Baseline disease characteristics were similar.

A significantly higher proportion of patients treated with RZB achieved PASI 90 (57.3% vs 22.9%, P < .0001), sPGA 0/1 (80.2% vs 39.7%, P < .0001), PASI 100 (27.5% vs 6.5%, P < .0001), and sPGA 0 (27.5% vs. 6.9%, P < .0001) compared with patients treated with DEU.

The proportion of patients with treatment-emergent adverse events was 33.6% (RZB) and 42.9% (DEU). The proportion of patients with adverse events related to study drug was 6.1% (RZB) and 15.3% (DEU). One serious adverse event of joint injury was reported by a patient receiving RZB, deemed unrelated to the study drug. There were no deaths reported.

Conclusion Treatment with RZB provided greater clinical response compared with DEU in adults with moderate PsO, and safety results were consistent with the known safety profile of RZB and DEU. These results support the opportunity to elevate treatment outcomes in biologic naïve patients with moderate PsO.