Remibrutinib inhibits human mast cell and basophil activation induced by serum from Chronic Urticaria patients independently of FcεR1 expression

Background: We aim to investigate the effects of the Bruton’s tyrosine kinase (BTK) inhibitor remibrutinib on human in vitro cell activation induced by serum obtained from chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU) patients. Methods: 22 patients with CSU (mean age 52 years, 27% women) and 22 with CIndU (46 years, 27% women) were included. A sex-equivalent control group was enrolled. Total IgE serum levels and the FcεR1a expression on blood basophils were determined before the initiation of omalizumab therapy. Patients were then classified as responders or non-responders to anti-IgE therapy, according to their clinical data and IgE and FcεR1a receptor expression. Mast cell generation and stimulation and basophil stimulation were performed. Flow cytometry was used to analyze samples. Percentage of activation, degranulation and inhibition in basophils and mast cells are studied. Results: Main results show that remibrutinib inhibits mast cells and basophil degranulation induced by IgE cross-linking. Also, serum from patients induced a greater degranulation of mast cells and basophils compared to controls. We found that activation of mast cells and basophils by patient sera was not related to omalizumab responsiveness. Conclusion: Our results show that remibrutinib is able to inhibit the degranulation of human basophils and mast cells in vitro, independently of the patient’s expression of FcεR1 expression and response to omalizumab.