Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response

by Selleckchem | Sep 18 2023

Background: Despite advances in the treatment of chronic urticaria, in a significant percentage of the patients symptoms are not fully controlled with conventional approaches. New strategies under development include blocking intracellular mediators of mast cell and basophil activation.

Objective: We aim to investigate the effects of the Bruton's tyrosine kinase (BTK) inhibitor remibrutinib on human blood basophils and CD34+ -derived mast cells activation induced by serum obtained from chronic urticaria patients.

Methods: Twenty-two patients with chronic spontaneous urticaria (mean age 52 years, 27% women) and 22 patients with chronic inducible urticaria (46 years, 27% women) were included in the study together with a sex-matched control group. Patients were classified as responders or non-responders to anti-IgE therapy on the basis of their clinical data, FcεR1a expression on blood basophils and total IgE levels. Changes on CD63 expression-as an activation marker-, were used to evaluate in vitro the response of basophils and mast cells to serum exposure and the inhibitory effects of remibrutinib.

Results: Remibrutinib inhibits degranulation induced by IgE cross-linking in mast cells and basophils and also the activation triggered by factors present in the sera of spontaneous and inducible chronic urticaria patients. Patient's serum induces a greater degranulation of effector cells than controls. Activation of mast cells and basophils by patient sera and remibrutinib effects were not related to omalizumab responsiveness.

Conclusion: Remibrutinib inhibits activation of human basophils and mast cells induced in vitro by exposure to the serum of chronic urticaria patients independently of their response to omalizumab.

Comments:

The study aimed to investigate the effects of remibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, on the activation of human blood basophils and CD34+-derived mast cells induced by serum obtained from patients with chronic urticaria. Chronic urticaria is a condition characterized by recurrent hives and itching, and conventional treatment approaches may not fully control symptoms in a significant percentage of patients.

The study included 22 patients with chronic spontaneous urticaria and 22 patients with chronic inducible urticaria, along with a control group of similar sex distribution. The patients were classified as responders or non-responders to anti-IgE therapy based on their clinical data, FcεR1a expression on blood basophils, and total IgE levels. Changes in CD63 expression, an activation marker, were used to assess the response of basophils and mast cells to serum exposure and the inhibitory effects of remibrutinib in vitro.

The results showed that remibrutinib inhibited degranulation, which is the release of inflammatory mediators, induced by IgE cross-linking in both mast cells and basophils. The drug also inhibited the activation triggered by factors present in the sera of patients with spontaneous and inducible chronic urticaria. It was observed that the serum from chronic urticaria patients induced greater degranulation in effector cells compared to the control group. Importantly, the activation of mast cells and basophils by patient sera and the inhibitory effects of remibrutinib were not dependent on the responsiveness of patients to omalizumab, another therapeutic option for chronic urticaria.

In conclusion, the study demonstrated that remibrutinib effectively inhibits the activation of human basophils and mast cells induced in vitro by exposure to serum from patients with chronic urticaria. This inhibition was independent of the patients' response to omalizumab treatment. These findings suggest that remibrutinib may be a promising strategy for controlling symptoms in chronic urticaria patients who do not respond to conventional approaches. Further research and clinical trials are warranted to validate these findings and explore the potential of remibrutinib as a treatment option for chronic urticaria.