A Phase 3b Study Evaluating Safety and Efficacy of Risankizumab in Adult Patients with Moderate-to-Severe Plaque Psoriasis with Palmoplantar (Non-Pustular) Involvement

Abstract

Introduction: We evaluate safety and efficacy of risankizumab (RZB) vs. placebo (PBO) in adult patients with moderate-to-severe non-pustular palmoplantar psoriasis (PPPsO). Method: IMMprint, a Ph3b study evaluated safety and efficacy of RZB vs. PBO in moderate-to-severe PPPsO patients with a static physician’s global assessment(sPGA) of moderate or severe ≥3, palmoplantar psoriasis area and severity index(PPASI) ≥8 and at least 1 additional PsO plaque. The 52-week treatment was split into period A, patients randomized (1:1) to RZB 150-mg or PBO, and period B, patients continuing RZB or switching from PBO to RZB (PBO/RZB). Primary endpoint was achievement of palmoplantar investigator’s global assessment (ppIGA) 0/1 with at least 2-point reduction from baseline at Wk16. Ranked secondary endpoints include ≥75% & 90% improvement in PPASI (PPASI75, PPASI90), sPGA 0/1 and 100% improvement in PPASI(PPASI100) at Wk16. Results: Of 174 enrolled, 87(mean age[SD]: 56.9[12.9] years) were randomized to RZB and 87(mean age[SD]: 53.9[14.3] years) were randomized to PBO. Baseline characteristics were similar except for numerical difference in PsA (RZB vs. PBO: 11.5% vs 4.6%, respectively). At Wk16, a significantly higher proportion receiving RZB achieved ppIGA 0/1 than PBO(33.3% vs. 16.1%, p = 0.006). Patients receiving RZB also demonstrated significantly higher responses than patients receiving PBO in all ranked secondary endpoints: PPASI75 (42.5% vs 14.9%, P < 0.001); PPASI90 (27.6% vs 5.7%, p<0.001); sPGA 0/1 (32.2% vs 11.5%, p < 0.001); and PPASI100 (17.2% vs. 1.1%, p < 0.001). Four patients (3 RZB: 1 PBO) discontinued drug in period A. At Wk52, ppIGA 0/1 was achieved by 50.6% of RZB patients and 61.7% of PBO/RZB group. Proportion of patients achieving PPASI75 at Wk52 was 57.5%(RZB) vs. 65.4% (PBO/RZB). Achievement of sPGA 0/1 (%RZB vs. %PBO/RZB) was 43.7% vs. 66.7%; PPASI100 was achieved by 26.4% (RZB) and 37.0% (PBO/RZB) patients at Wk52. Proportion of patients with adverse events were 29.1%(RZB) and 23.0%(PBO) in period A, and 49.4%(RZB) and 35.8% (PBO/RZB) in period B. One RZB patient with prior cardiovascular risk factors had an adjudicated myocardial infarction and subsequently died after 140-day follow-up period. The number of patients with COVID-19 were 3 (RZB; 1 serious infection) and 2(PBO) in period A and 11 (RZB) and 7 (PBO/RZB) in period B. Conclusion: This study demonstrates RZB can provide effective improvement compared to PBO by Wk16 with continuous improvement until Wk52 with no new safety signals in patients with moderate-to-severe PPPsO.