Remibrutinib in chronic spontaneous urticaria: 52-week results from two phase 3 studies

Background: Remibrutinib, an oral, highly selective Bruton tyrosine kinase inhibitor, demonstrated significant improvements in disease activity over placebo in the 24-week phase 3 REMIX studies in patients with chronic spontaneous urticaria (CSU) remaining symptomatic despite second-generation H₁-antihistamines. Objective: We sought to evaluate the long-term efficacy and safety of remibrutinib in patients with CSU. Methods: REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) were two randomized placebo-controlled studies evaluating the efficacy, safety, and tolerability of remibrutinib in patients with CSU. Patients were randomized 2:1 to receive oral remibrutinib 25 mg twice daily or placebo during a 24-week double-blind placebo-controlled period, followed by a 28-week open-label treatment period (up to 52 weeks). The primary end point was change from baseline in weekly Urticaria Activity Score at week 12. Results: A total of 470 patients in REMIX-1 and 455 in REMIX-2 were randomly assigned to receive remibrutinib (n = 313 and 300, respectively) or placebo (n = 157 and 155, respectively). At week 52, patients randomized to remibrutinib showed sustained improvements in change from baseline in weekly Urticaria Activity Score (mean [95% confidence interval], REMIX-1: −23.22 [−24.78, −21.66]; REMIX-2: −22.98 [−24.51, −21.44]), with similar responses observed in patients who transitioned from placebo to remibrutinib at week 24 (observed as early as 1 week after transitioning). Exposure-adjusted incidence rates of adverse events, serious adverse events, and adverse events leading to discontinuation with 52-week remibrutinib treatment remained equivalent to those in the 24-week analysis. Conclusion: Remibrutinib showed sustained efficacy and a consistent, favorable long-term safety profile in patients with CSU remaining symptomatic despite second-generation H₁-antihistamines.