Spesolimab for generalized pustular psoriasis: A prospective study with a 6-month-follow-up.

Abstract

Generalized pustular psoriasis (GPP) is a rare, life-threatening skin disease. Spesolimab, an anti-IL-36R monoclonal antibody, has shown efficacy in clinical trials, yet real-world data remain limited. To evaluate the real-world effectiveness and safety of spesolimab in patients with GPP, and the influence of IL36RN mutation status on treatment response. A prospective study was conducted including patients with GPP treated with a single 900 mg intravenous infusion of spesolimab, with follow-ups at day 7, 1 month, 3 months, and 6 months. Disease severity was assessed using the GPPASI score. Screening of the IL36RN c.80T>C (p.L27P) mutation was performed using Sanger sequencing. Fourteen patients (n=14) (9 women, 5 men; mean age 39.1 years) were included. The mean baseline GPPASI score was 3.61, which rapidly decreased to 1.3 at day 7, 0.52 at 1 month and 0.29 at 3 months, yet slightly increased to 0.35 at 6 months. The Wilcoxon signed-rank test confirmed a statistically significant decrease in GPPASI over time (p<0.05) from baseline which persisted till the third month. Three relapses occurred during follow-up, and they all responded to acitretin reintroduction. Among the 12 patients tested, 7 carried the IL36RN c.80T>C (p.L27P) mutation in the homozygous state. Treatment response was slightly faster in these patients but there were no statistically significant differences, and the 2 groups converged by the third month. No adverse events were observed. Spesolimab demonstrated rapid and marked efficacy with excellent tolerability in GPP flares, regardless of IL36RN mutation status. Most cases had sustained remission, yet relapse occurred in a minority of patients. This calls for further research to optimize long-term and maintenance therapy.