IgE signaling through its high-affinity receptor FcεRI is central to the pathogenesis of numerous allergic disorders. Oral inhibitors of Bruton's tyrosine kinase (BTKis), which are currently Food and Drug Administration-approved for treating B cell malignancies, broadly inhibit the FcεRI pathway in human mast cells and basophils, and therefore may be effective allergen-independent therapies for a variety of allergic diseases. The application of these drugs to the allergy space was previously limited by the low kinase selectivity and subsequent toxicities of early-generation compounds. Fortunately, next-generation, highly selective BTKis in clinical development appear to have more favorable risk-benefit profiles, and their likelihood of being Food and Drug Administration-approved for an allergy indication is increasing. Recent clinical trials have indicated the remarkable and rapid efficacy of the second-generation BTKi acalabrutinib in preventing clinical reactivity to peanut ingestion in adults with peanut allergy. In addition, next-generation BTKis including remibrutinib effectively reduce disease activity in patients with antihistamine-refractory chronic spontaneous urticaria. Finally, several BTKis are currently under investigation in early clinical trials for atopic dermatitis and asthma. In this review, we summarize recent data supporting the use of these drugs as novel therapies in food allergy, anaphylaxis, urticaria, and other allergic disorders. We also discuss safety data derived from trials using both short-term and chronic dosing of BTKis.

中文翻译：

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布鲁顿酪氨酸激酶抑制治疗过敏性疾病

通过其高亲和力受体 FcεRI 的 IgE 信号传导对于许多过敏性疾病的发病机制至关重要。布鲁顿酪氨酸激酶 (BTKis) 的口服抑制剂目前已获得美国食品和药物管理局批准用于治疗 B 细胞恶性肿瘤，广泛抑制人类肥大细胞和嗜碱性粒细胞中的 FcεRI 通路，因此可能是多种非过敏原有效的治疗方法过敏性疾病。这些药物在过敏领域的应用此前因早期化合物的低激酶选择性和随后的毒性而受到限制。幸运的是，临床开发中的下一代、高度选择性的 BTK 似乎具有更有利的风险效益特征，并且它们获得美国食品和药物管理局批准用于过敏适应症的可能性正在增加。最近的临床试验表明，第二代 BTKi acalabrutinib 在预防患有花生过敏的成人对花生摄入的临床反应方面具有显着且快速的功效。此外，包括瑞米布替尼在内的新一代 BTK 可以有效降低抗组胺药难治性慢性自发性荨麻疹患者的疾病活动度。最后，目前正在研究几种 BTK 治疗特应性皮炎和哮喘的早期临床试验。在这篇综述中，我们总结了支持使用这些药物作为食物过敏、过敏反应、荨麻疹和其他过敏性疾病的新疗法的最新数据。我们还讨论了从短期和长期服用 BTK 的试验中得出的安全性数据。