Bruton's tyrosine kinase inhibition - An emerging therapeutic strategy in immune-mediated dermatological conditions

Funding Information: PM‐B received honoraria for acting as a consultant and/or as a speaker for AbbVie, Janssen, Novartis, LEO Pharma, Almirall, Sanofi, Viatris, L’Oréal, and Cantabria Labs and served as a principal investigator in clinical trials supported by AbbVie, Sanofi, and Novartis. AB received honoraria for lectures and educational events for LEO Pharma, Janssen‐Cilag, AbbVie, and Novartis. PK received payment/honoraria for lectures/presentations outside of submitted work for Novartis and Roche.. SM‐R received funding from GA²LEN Global Allergy and Asthma European Network. MM served as a speaker and/or advisor for and/or has received research funding from Allakos, Amgen, Aralez, ArgenX, AstraZeneca, Blueprint, Celldex, Centogene, CSL Behring, FAES, Genentech, Gilead, GIInnovation, Innate Pharma, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Moxie, Novartis, Roche, Sanofi/Regeneron, Third Harmonic Bio, UCB, and Uriach. SF and JS have no conflicts of interest to disclose. Funding Information: We acknowledge Becky Fox‐Spencer, Ph.D. (on behalf of Bedrock Healthcare Communications), who provided writing support for this manuscript, funded by Novartis Pharma AG (Basel, Switzerland). Publisher Copyright: © 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B-cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune-mediated dermatological diseases. However, the established risk-to-benefit profile of “first-generation” BTK inhibitors cannot be extrapolated to these emerging, non-oncological, indications. “Next-generation” BTK inhibitors such as remibrutinib and fenebrutinib entered clinical development for chronic spontaneous urticaria (CSU); rilzabrutinib and tirabrutinib are being studied as potential treatments for pemphigus. Promising data from early-phase clinical trials in CSU suggest potential for these agents to achieve strong pathway inhibition, which may translate into measurable clinical benefits, as well as other effects such as the disruption of autoantibody production. BTK inhibitors may help to overcome some of the shortcomings of monoclonal antibody treatments for immune-mediated dermatological conditions such as CSU, pemphigus, and systemic lupus erythematosus. In addition, the use of BTK inhibitors may improve understanding of the pathophysiological roles of mast cells, basophils, and B cells in such conditions. publishersversion published