Gimeno, Ramon, Ribas-Llaurado, Clara, Pesque, David, Andrades, Evelyn, Cenni, Bruno, Ambros, Barbara, Pujol, Ramon and Gimenez-Arnau, Ana Maria (2023) Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response. Clinical and Translational Allergy, 13 (3). ISSN 2045-70222045-7022

Abstract

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.

Item Type:	Article
Date Deposited:	18 Mar 2023 00:45
Last Modified:	18 Mar 2023 00:45
URI:	https://oak.novartis.com/id/eprint/47304