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

Generalized pustular psoriasis (GPP) is a rare, life-threatening skin disease. Spesolimab, an anti-interleukin (IL)-36R monoclonal antibody, has shown efficacy in clinical trials, yet real-world data remain limited. We evaluated 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-up at 1 week, 1 month, 3 months and 6 months. Disease severity was assessed using the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Screening for the IL36RN c.80T>C(p.L27P) mutation was performed using Sanger sequencing. In total, 14 patients (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 to 3 months. Three relapses occurred during follow-up and 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 two groups converged by 3 months. 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.