Background: Many patients with chronic spontaneous urticaria (CSU) fail to achieve symptom control despite maximal-dose H1-antihistamines or omalizumab, creating a need for new oral therapies.
Objective: This review aims to systematize the pathogenesis related to Bruton tyrosine kinase (BTK) and the clinical evidence on the efficacy and safety of BTK inhibitors in CSU treatment.
Methods: A systematic search of PubMed/MEDLINE, Google Scholar, and the FDA website (January 2018–June 2026) used the keywords “Bruton tyrosine kinase,” “BTK inhibitor,” “chronic spontaneous urticaria,” “remibrutinib,” “fenebrutinib,” and “rilzabrutinib”; randomized controlled trials and international guidelines were prioritized.
Results: BTK, a key kinase downstream of FcεRI on mast cells and basophils, drives degranulation and histamine release in CSU. Remibrutinib, an oral selective BTK inhibitor, gained FDA approval in September 2025 based on phase III REMIX-1/REMIX-2 trials, showing significant UAS7 improvement over placebo, rapid onset, and sustained efficacy through week 52. Fenebrutinib and rilzabrutinib have also shown promising phase II results.
Conclusion: BTK inhibitors, led by remibrutinib, represent a new oral targeted treatment option for antihistamine-refractory CSU, with the potential to complement current injectable therapies. Further real-world and Vietnam-based data are needed to define its optimal role.