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布鲁顿酪氨酸激酶抑制剂在过敏领域的现状与未来前景

Current and future landscape of Bruton tyrosine kinase inhibitors in allergy.

作者信息

Lin Erica V, Arce Betania, Alvarez-Arango Santiago, Dispenza Melanie C

机构信息

Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.

Departments of Medicine and Pediatrics, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, Tex.

出版信息

J Allergy Clin Immunol. 2025 Jun 16. doi: 10.1016/j.jaci.2025.05.030.

Abstract

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.

摘要

作为FcεRI途径的重要组成部分,布鲁顿酪氨酸激酶(BTK)已成为治疗过敏性疾病的靶点。几项使用第一代化合物(如伊布替尼和阿卡替尼)的概念验证研究表明,短期使用BTK抑制剂(BTKis)能够降低皮肤对过敏原的测试反应,抑制嗜碱性粒细胞激活反应,甚至完全预防人类对过敏性食物摄入的反应。虽然第一代BTKis对于非肿瘤适应症的长期给药没有可接受的不良反应谱,但正在研发的新型化合物对BTK具有更高的选择性和更少的不良反应。特别是,瑞布替尼在慢性自发性荨麻疹的长期给药中已显示出显著的疗效和安全性,有望成为美国首个获批用于过敏领域的BTKi。本综述总结了使用BTKis治疗过敏性疾病的研究工作,重点强调了临床医生在安全性和实际应用方面的考虑因素。

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