Risankizumab in Japanese patients with moderate-to-severe palmoplantar pustulosis: Results from the randomized, phase 3 JumPPP study

Abstract

Palmoplantar pustulosis (PPP) is a chronic, debilitating skin disease of the palms and/or soles. We report the efficacy and safety of risankizumab (RZB), an interleukin 23 p19 inhibitor, from the JumPPP study (a phase 3, multicenter, randomized, placebo-controlled, double-blind study to evaluate RZB in adult Japanese sUbjects with Moderate-to-severe PalmoPlantar Pustulosis; NCT04451720). Patients were randomized 1:1 to receive RZB (150 mg) or placebo at weeks 0 and 4; all patients received RZB from week 16 to week 52 (patients initially randomized to RZB) or week 56 (patients initially randomized to placebo). The primary end point was a Palmoplantar Pustulosis Area and Severity Index (PPPASI) change from baseline; secondary end points were ≥50%/≥75% improvement in PPPASI (PPPASI 50/75) at week 16. Efficacy and safety were evaluated to 68 and 76 weeks, respectively. In total, 119 patients (RZB, n = 61; placebo, n = 58) were enrolled. Greater improvement with RZB versus placebo was demonstrated by the significant difference in PPPASI change from baseline at week 16 (least squares mean treatment difference, -3.48; p < 0.05). At week 16, a greater proportion of patients receiving RZB vs placebo achieved PPPASI 50 (41.0% vs 24.1%; nominal p < 0.05) but not PPPASI 75 (13.1% vs 15.5%; nominal p = 0.74). Improvements generally continued through to week 68. The safety profile was generally consistent with previous studies of RZB in psoriasis. RZB demonstrated efficacy over placebo at week 16 in Japanese patients with PPP, with improvements sustained through to week 68, and was well tolerated with no unexpected safety findings.

Keywords: Japan; Japanese; palmoplantar pustulosis; psoriasis; risankizumab.

FIGURE 1

Patient disposition. Data are presented as n (%).^aDiscontinued due to patient‐reported physical and mental burden. ^bDouble‐blind period (weeks 0–16). ^cDiscontinued due to lack of efficacy. ^dDiscontinued due to alcoholic steatohepatitis (one patient) and hepatocellular carcinoma (one patient). ^eDiscontinued due to unrelated health concerns. ^fRisankizumab (RZB)‐treatment period (weeks 16–68). PBO, placebo.

FIGURE 2

Palmoplantar Pustulosis Area and Severity Index (PPPASI) outcomes. For change from in PPPASI total score from baseline, a mixed‐effect model for repeated measures was used in the double‐blind period (Period A; weeks 0–16) and included the fixed effects of treatment, visit, treatment‐by‐visit interaction, baseline smoking status, and baseline measurement as covariates. For a ≥50% or ≥75% improvement in PPPASI (PPPASI 50/75), non‐responder imputation while incorporating multiple imputation to handle missing data due to COVID‐19 was used in the placebo‐controlled period (Period A; weeks 0–16); missing data due to COVID‐19 infection or logistical restriction were handled by multiple imputation. Observed‐cases analysis was used in the risankizumab (RZB)‐treatment period (Period B; weeks 16–68); observed‐cases analysis did not impute values for missing data, and patients missing data were excluded from the observed analysis for that visit. The dotted line represents the end of Period A. ^aEnd of RZB treatment in RZB‐RZB arm. ^bEnd of RZB treatment in the placebo (PBO)‐RZB arm. CI, confidence interval; LS, least squares. *p < 0.05 versus PBO; p values for PPPASI 50/75 are nominal.

FIGURE 3

Change from baseline in modified Bath Ankylosing Spondylitis Disease Activity Index (mBASDAI) among patients with baseline pustulotic arthro‐osteitis (PAO). PAO diagnosis was confirmed by magnetic resonance imaging. A mixed‐effect model for repeated measures was used in the double‐blind period (Period A; weeks 0–16) and included the fixed effects of treatment, visit, treatment by visit interaction, baseline smoking status, and baseline measurement as covariates. Observed‐cases analysis was used in the risankizumab (RZB)‐treatment period (Period B; weeks 16–68); observed‐cases analysis did not impute values for missing data, and patients missing data were excluded from the observed analysis for that visit. The dotted line represents the end of Period A. ^aEnd of RZB treatment in RZB‐RZB arm. ^bEnd of RZB treatment in placebo (PBO)‐RZB arm. CI, confidence interval; LS, least squares.

FIGURE 4

Change from baseline in worst pruritus numeric rating scale (WP‐NRS) and Dermatology Life Quality Index (DLQI). A mixed‐effect model for repeated measures was used in the double‐blind period (Period A; weeks 0–16) and included the fixed effect of treatment, visit, treatment by visit interaction, baseline smoking status, and baseline measurement as covariates. Observed‐cases analysis was used in the risankizumab (RZB)‐treatment period (Period B; weeks 16–68); observed‐cases analysis did not impute values for missing data, and patients missing data were excluded from the observed analysis for that visit. The dotted line represents the end of Period A. ^aEnd of RZB treatment in RZB‐RZB arm. ^bEnd of RZB treatment in placebo (PBO)‐RZB arm. CI, confidence interval; LS, least squares; PBO, placebo.