Efficacy and Safety of Remibrutinib in Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis

BACKGROUND: Chronic spontaneous urticaria (CSU) is a dermatologic condition defined by recurrent wheals, angioedema, or both for ≥6 weeks. Although current treatments such as second-generation H1-antihistamines and omalizumab improve symptoms, many patients remain uncontrolled. Remibrutinib, a highly selective oral Bruton tyrosine kinase inhibitor, is a promising novel therapy. This meta-analysis evaluated its efficacy and safety in antihistamine-refractory CSU. DATA SOURCES: A systematic search of PubMed, Embase, Cochrane Library, Scopus, Web of Science, and clinicaltrials.gov was conducted through March 2025. Only randomized controlled trials reporting UAS7, ISS7, HSS7, and safety data were included. Risk of bias was assessed using Cochrane RoB 2.0, and statistical analyses were performed using RevMan 5.4.1. MAIN FINDINGS AND LIMITATIONS: Three randomized controlled trials (n = 997) were included. Remibrutinib significantly improved disease control versus placebo, with higher odds of achieving UAS7 ≤ 6 (odds ratios 4.38; P < 0.0001) and greater reductions in UAS7 scores (MD -9.45; P < 0.00001). Complete response (UAS7 ≤ 0) was not statistically significant (odds ratios 2.14; P = 0.16). Mild infections, nasopharyngitis, petechiae, and URTIs were more frequent with remibrutinib, while overall adverse events, serious events, and discontinuations were similar. CONCLUSIONS: Remibrutinib demonstrates significant efficacy and an overall favorable short-term safety profile for refractory CSU, though increased mild infections warrant monitoring. Larger, long-term studies and direct comparisons with omalizumab are needed.