Safety of Remibrutinib in Chronic Spontaneous Urticaria: A Pooled Analysis of REMIX-1 and REMIX-2 Trials

BACKGROUND: Remibrutinib, an oral, highly selective Bruton's tyrosine kinase inhibitor, showed sustained efficacy in phase 3 REMIX trials in chronic spontaneous urticaria. OBJECTIVE: To report detailed safety outcomes from the REMIX trials, including key findings pertinent to Bruton's tyrosine kinase inhibitor safety, such as bleeding, infections, cytopenia, and liver safety. METHODS: This was a pooled analysis of REMIX-1 and REMIX-2 consisting of a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week open-label treatment period. Adverse event (AE) frequencies and laboratory parameters were examined through week 52, and differences versus placebo were evaluated in the controlled period. RESULTS: AE frequencies and risk differences (95% CI) for remibrutinib (n = 606) versus placebo (n = 306) were as follows: any AE 64.9% versus 64.7%, difference 0.1% (-6.4% to 6.7%); bleeding (including laboratory abnormalities) 10.6% versus 5.2%, difference 5.3% (1.6% to 8.7%); infections 33.5% versus 34.3%, difference -0.8% (-7.4% to 5.6%); cytopenia AEs 3.6% versus 2.0%, difference 1.7% (-0.7% to 3.8%); hepatic disorders 3.3% versus 4.9%, difference -1.6% (-4.6% to 1.1%). Imbalance in bleeding was due to petechia and similar mucocutaneous events (predominantly mild, none severe) occurring in 9.1% of patients on remibrutinib versus 2.0% of patients on placebo. No other AEs with significantly increased frequency occurred on remibrutinib. Findings during the entire study period were consistent with those in the controlled period. CONCLUSIONS: Remibrutinib showed a favorable safety profile with slightly higher incidence of petechia and similar predominantly mild mucocutaneous events. There were no notable differences in the frequency of other safety outcomes between remibrutinib and placebo in the REMIX trials.