The efficacy and safety of spesolimab in patients with generalized pustular psoriasis flares: a systematic review and meta-analysis

Background: Generalized pustular psoriasis (GPP) is a rare, auto-inflammatory skin disease characterized by unpredictable flares, often requiring hospitalization, and current therapies lack robust evidence. Objectives: To systematically evaluate the efficacy and safety of spesolimab for acute GPP flares. Methods: We searched Medline, Google Scholar and the Cochrane Central Register of Controlled Trials from inception to December 2024 and consulted ClinicalTrials.gov and the ISRCTN registry for ongoing studies. Randomized controlled trials enrolling adults experiencing GPP flares and comparing spesolimab with placebo or standard care were eligible. Non-randomized studies, studies without placebo comparators, or without full-text availability were excluded. Two reviewers independently assessed risk of bias using the Cochrane RoB 2 tool and extracted data. A random-effects model was used to pool odds ratios or mean differences with 95% confidence intervals. Results: Four randomized controlled trials with 176 participants met the inclusion criteria. Compared with placebo, spesolimab significantly increased the proportion of patients achieving complete pustular clearance [GPPGA pustulation score 0; OR 4.87 (95% CI 2.03-11.68)] and a total GPPGA score of 0 or 1 [OR 5.68 (95% CI 2.27-14.23)]. Adverse event rates were similar between groups and were mostly mild or moderate. Limitations: Evidence was limited by the small number and sample size of trials, heterogeneity between studies and short follow-up durations. Conclusion: Spesolimab provides clinically meaningful improvements in pustular clearance and symptom control during acute GPP flares and has a favorable safety profile; however, further large, long-term randomized trials are needed. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42025629994, identifier CRD42025629994.