INTRODUCTION
Chronic spontaneous urticaria (CSU) is a chronic, debilitating condition characterized by recurrent wheals and/or angioedema.1 Symptoms occur daily or nearly daily for at least 6 weeks, with angioedema reported in up to 50% of patients without an identifiable external trigger.1-3 The disease affects approximately 0.5% to 1% of the general population, with a higher prevalence in women, and most commonly presents between 20 and 40 years of age.2 For the majority of patients, CSU persists for 1 to 5 years, although cases with more severe disease may last longer, contributing substantially to impaired quality of life.2
The pathogenesis of CSU is predominantly mediated by mast cell degranulation, though the exact mechanisms by which mast cells are activated are not completely known.4 Additional contributions are from eosinophils and basophils, which release vasoactive mediators involved in urticaria.1,5,6 A wide range of cytokines and chemokines have been linked to CSU, providing the rationale for emerging targeted therapies.5
Bruton tyrosine kinase (BTK), a member of the TEC family of cytoplasmic protein tyrosine kinases, is expressed across multiple cell types and forms part of the signal transduction of mast cell degranulation.7,8 Targeting of BTK has been explored for the treatment of several B-cell driven diseases, leading to approval by the Food and Drug Administration (FDA) for therapies such as ibrutinib, acalabrutinib, and zanubrutinib.9-11 Given the role of BTK in the pathogenesis of CSU, there is increasing literature demonstrating the efficacy of BTK inhibition for the treatment of this disease.
The pathogenesis of CSU is predominantly mediated by mast cell degranulation, though the exact mechanisms by which mast cells are activated are not completely known.4 Additional contributions are from eosinophils and basophils, which release vasoactive mediators involved in urticaria.1,5,6 A wide range of cytokines and chemokines have been linked to CSU, providing the rationale for emerging targeted therapies.5
Bruton tyrosine kinase (BTK), a member of the TEC family of cytoplasmic protein tyrosine kinases, is expressed across multiple cell types and forms part of the signal transduction of mast cell degranulation.7,8 Targeting of BTK has been explored for the treatment of several B-cell driven diseases, leading to approval by the Food and Drug Administration (FDA) for therapies such as ibrutinib, acalabrutinib, and zanubrutinib.9-11 Given the role of BTK in the pathogenesis of CSU, there is increasing literature demonstrating the efficacy of BTK inhibition for the treatment of this disease.
Existing Therapeutic Options for Chronic Spontaneous Urticaria
First-line therapeutic options for CSU are second-generation H1-antihistamines.12 These include bilastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, and rupatadine.12 However, >50% of patients who receive this treatment continue to experience symptoms of CSU and 75% have sustained symptoms despite increasing dosage up to 4 times the standard dose.13-16 For individuals who are not controlled
First-line therapeutic options for CSU are second-generation H1-antihistamines.12 These include bilastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, and rupatadine.12 However, >50% of patients who receive this treatment continue to experience symptoms of CSU and 75% have sustained symptoms despite increasing dosage up to 4 times the standard dose.13-16 For individuals who are not controlled
