Efficacy, Safety, and Quality-of-Life Outcomes of Remibrutinib in Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis.

Abstract

Chronic spontaneous urticaria (CSU) is a mast cell-mediated condition affecting approximately 1% of the population and is often refractory to antihistamines and omalizumab. Remibrutinib, a Bruton's tyrosine kinase inhibitor, prevents mast cell activation independent of the IgE pathway. To assess the efficacy, safety, and quality-of-life outcomes of remibrutinib compared with placebo in adults with refractory CSU. A systematic review was conducted per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three randomized controlled trials (RCTs) (n = 997) and 2 single-arm studies (n = 280) evaluating remibrutinib in CSU were included. Specific disease activity end points assessed included changes in Urticaria Activity Score over 7 days (UAS7), Hives Severity Score over 7 days, Itch Severity Score over 7 days, Angioedema Activity Score over 7 days, and Dermatology Life Quality Index. The risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool for RCTs and Risk of Bias in Non-randomized Studies of Interventions for single-arm studies. Meta-analysis was performed using a random-effects model. In the pooled analysis of RCTs, remibrutinib effectively decreased UAS7 at week 12 compared with placebo (mean difference, -7.81; 95% CI, -10.29 to -5.33), with improvements in itch and hives severity scores (mean difference, -2.94, 95% CI, -3.73 to -2.15, and mean difference, -4.05, 95% CI, -4.98 to -3.12, respectively). Remibrutinib increased the likelihood of achieving complete response (UAS7 = 0: risk ratio [RR], 3.32; 95% CI, 2.34 to 4.71), controlled disease (UAS7 ≤ 6: RR, 2.13; 95% CI, 1.73 to 2.62), and minimal quality-of-life impact (Dermatology Life Quality Index ≤ 1: RR, 1.84; 95% CI, 1.47 to 2.30). REMIX-1 and REMIX-2 trials showed significantly better disease control (UAS7 ≤ 6) by week 2 (RR, 6.81; 95% CI, 3.45 to 13.42). Adverse event rates with remibrutinib were similar to those with placebo, except for increased nasopharyngitis, upper respiratory tract infection, and petechiae (RR, 1.88, 95% CI, 1.11 to 3.19; RR 2.88, 95% CI, 1.30 to 6.41; and RR, 7.52, 95% CI, 1.44 to 39.20, respectively). Evidence from single-arm studies (BISCUIT at 24 weeks and Jain 2024 at 52 weeks) suggested sustained long-term efficacy and tolerability. Remibrutinib shows rapid symptom improvement with an acceptable safety profile in refractory CSU and appears to be a promising oral option for antihistamine-refractory CSU based on short-term data.