Efficacy of Risankizumab Compared to Ustekinumab in Patients with Moderate-to-Severe Plaque Psoriasis Affecting High-Impact Areas: An Integrated Post hoc Analysis of the Phase 3 UltIMMa-1 and UltIMMa-2 Trials

Introduction: Psoriasis involving high-impact areas (HIA) such as nails, scalp, and palms or soles can significantly affect quality of life, and traditional body surface area (BSA)-based severity classification may fail to capture the true patient burden in these patients. In 2 randomized, double-blind, placebo-controlled phase 3 trials (NCT02684370, NCT02684357), risankizumab (RZB) was superior to ustekinumab (UST) for treating moderate-to-severe plaque psoriasis. We conducted an integrated post hoc analysis of RZB and UST efficacy in psoriasis involving HIA. Materials/Methods: Eligible patients had stable moderate-to-severe chronic plaque psoriasis for ≥6 months, BSA involvement ≥10%, baseline Psoriasis Area Severity Index (PASI) score ≥12, and static Physician’s Global Assessment (sPGA) score ≥3. Patients were included in the HIA analysis if they had a baseline score >0 on the Nail Psoriasis Severity Index, Psoriasis Scalp Severity Index, or Palmoplantar Psoriasis Area Severity Index. Patients received subcutaneous RZB 150 mg, or UST per label (45 mg or 90 mg) at weeks 0, 4, 16, 28, and 40. Achievement of 90% and 100% improvement on the PASI (PASI 90 and PASI 100) and a Dermatology Life Quality Index (DLQI) score of 0 or 1 were assessed through week 52 and stratified by baseline sPGA score (3 or 4). Results: A total of 759 patients (n=569 RZB, n=190 UST) had psoriasis affecting a HIA, including 484, 714, and 240 patients with nail, scalp, and palmoplantar psoriasis, respectively. Patients treated with RZB and UST were primarily male (69.2% and 69.5%), had a mean age of 47.2 and 47.3 years, had a mean PASI score of 20.5 and 19.0, and an sPGA score of 4 was reported in 19.0% and 15.8% of patients, respectively. Mean baseline DLQI scores were 13.3 and 12.7, respectively. At week 52, among patients with any HIA involvement and sPGA=3, PASI 90 was achieved by 80.7% of RZB-treated patients versus 47.5% of UST-treated patients. PASI 100 was achieved by 58.8% versus 28.1%, respectively. DLQI scores of 0 or 1 were reported by 72.0% of RZB-treated patients versus 45.6% of UST-treated patients. Among those patients with either nail, scalp, or palmoplantar psoriasis and sPGA=3, PASI 90 was achieved by 77.6%, 81.3%, and 76.9% of RZB-treated patients versus 41.7%, 48.0%, and 40.0% of UST-treated patients, respectively. Among those patients with psoriasis affecting any HIA and sPGA=4, PASI 90 was achieved by 82.4% with RZB versus 46.7% with UST, and PASI 100 by 51.9% versus 13.3%, respectively. DLQI scores of 0 or 1 were reported by 80.6% of RZT-treated patients versus 50% of UST-treated patients. Among those patients with either nail, scalp, or palmoplantar psoriasis and sPGA=4, PASI 90 was achieved by 81.3%, 83.0%, and 75.8% of RZB-treated patients versus 42.1%, 46.4%, and 27.3% of UST-treated patients, respectively. Conclusions: In this post hoc analysis of patients with nail, scalp, or palmoplantar involvement in UltIMMa-1 and UltIMMa-2, almost twice as many patients receiving RZB than UST achieved clear or almost clear skin and reported little to no impact of psoriasis on quality of life, regardless of baseline sPGA score (3 or 4).