Current and future landscape of Bruton tyrosine kinase inhibitors in allergy

As an essential component of the FcεRI pathway, Bruton tyrosine kinase (BTK) has become a target for treating allergic diseases. Several proof-of-concept studies using early-generation compounds such as ibrutinib and acalabrutinib demonstrated the ability of short courses of BTK inhibitors (BTKis) to reduce skin test responses to allergens, suppress basophil activation responses, and even completely prevent reactivity to allergenic food ingestion in humans. While early-generation BTKis do not have acceptable adverse effect profiles for chronic administration for nononcologic indications, newer compounds in development have higher selectivity for BTK and fewer adverse effects. In particular, remibrutinib has demonstrated remarkable efficacy and safety with chronic administration for chronic spontaneous urticaria and is poised to become the first BTKi approved in the United States for use in the allergy space. This review summarizes work using BTKis to treat allergic disorders, emphasizing safety and practical considerations for clinicians.