Ahmed Ali Khana b✉, Abdul Ahad Riaza c✉, F. Naseera d✉, N. Fatimaa e✉, Zuhair Abrara f✉, Linta Malika g✉, Jumana Khanh i✉, Raza Aslam
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BACKGROUND Chronic spontaneous urticaria (CSU) is a mast cell-mediated condition affecting ∼1% of the population and is often refractory to antihistamines and omalizumab. Remibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, prevents mast cell activation independent of the IgE pathway. OBJECTIVE To assess the efficacy, safety, and quality-of-life outcomes (QoL) of remibrutinib compared to placebo in adults with refractory CSU. METHODS A systematic review was conducted per PRISMA guidelines. Three RCTs (n=997) and two single-arm studies (n=280) evaluating remibrutinib in CSU were included. Specific disease activity endpoints assessed included changes in Urticaria Activity Score (UAS7), Hives Severity Score (HSS7), Itch Severity Score (ISS7), Angioedema Activity Score (AAS7), and Dermatology Life Quality Index (DLQI). The risk of bias was evaluated using the Cochrane RoB-2 tool for RCTs and ROBINS-I for single-arm studies. Meta-analysis was performed using a random-effects model. RESULTS In the pooled analysis of RCTs, remibrutinib effectively decreased UAS7 at Week 12 compared to placebo (MD -7.81, 95% CI: -10.29 to -5.33), with improvements in itch and hives severity scores (MD -2.94, 95% CI: -3.73 to -2.15, and MD -4.05, 95% CI: -4.98 to -3.12, respectively). Remibrutinib increased the likelihood of achieving complete response (UAS7=0; 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 (DLQI ≤ 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 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% Cl: 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. CONCLUSION 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.
TL;DRRemibrutinib 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. (Semantic Scholar)
