Clin Exp Dermatol. 2026 Apr 18:llag169. doi: 10.1093/ced/llag169. Online ahead of print.
ABSTRACT
BACKGROUND: 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.
OBJECTIVE: To evaluate the real-world effectiveness and safety of spesolimab in patients with GPP, and the influence of IL36RN mutation status on treatment response.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
PMID:41999186 | DOI:10.1093/ced/llag169