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布鲁顿酪氨酸激酶抑制剂治疗过敏疾病。

Bruton's tyrosine kinase inhibition for the treatment of allergic disorders.

机构信息

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

Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland.

出版信息

Ann Allergy Asthma Immunol. 2024 Jul;133(1):33-42. doi: 10.1016/j.anai.2024.03.002. Epub 2024 Mar 14.


DOI:10.1016/j.anai.2024.03.002
PMID:38492772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11222055/
Abstract

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.

摘要

IgE 信号通过其高亲和力受体 FcεRI 是许多过敏性疾病发病机制的核心。布鲁顿酪氨酸激酶(BTK)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 途径,因此可能是治疗多种过敏性疾病的有效过敏原非依赖性疗法。这些药物在过敏领域的应用以前受到第一代化合物激酶选择性低和随后毒性的限制。幸运的是,目前正在临床开发的新一代高选择性 BTK 抑制剂似乎具有更好的风险效益比,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 可显著快速预防花生过敏成人对花生摄入的临床反应。此外,包括 remibrutinib 在内的新一代 BTK 抑制剂可有效降低抗组胺难治性慢性自发性荨麻疹患者的疾病活动度。最后,几种 BTK 抑制剂目前正在早期临床试验中用于特应性皮炎和哮喘。在这篇综述中,我们总结了支持将这些药物作为新型疗法用于食物过敏、过敏反应、荨麻疹和其他过敏性疾病的最新数据。我们还讨论了从短期和慢性 BTK 给药试验中获得的安全性数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/11222055/cdeace66e53e/nihms-1977194-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/11222055/28a1fc08c9b3/nihms-1977194-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/11222055/cc003c7d768c/nihms-1977194-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/11222055/4e260fa78d4b/nihms-1977194-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/11222055/cdeace66e53e/nihms-1977194-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/11222055/28a1fc08c9b3/nihms-1977194-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/11222055/cc003c7d768c/nihms-1977194-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/11222055/4e260fa78d4b/nihms-1977194-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/11222055/cdeace66e53e/nihms-1977194-f0004.jpg

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引用本文的文献

[1]
The Bruton's tyrosine kinase inhibitor acalabrutinib aborts ongoing acute food-induced anaphylactic reactions in humanized mice.

J Allergy Clin Immunol. 2025-7-17

[2]
Aberrant Activation of Mast Cells: Molecular Mechanisms and Targets for Intervention.

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

J Allergy Clin Immunol. 2025-6-16

[4]
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[5]
Decoding the causal association between immune cells and three chronic respiratory diseases: Insights from a bi-directional Mendelian randomization study.

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[6]
Update on the Treatment of Chronic Spontaneous Urticaria.

Drugs. 2025-4

[7]
Clinical and Pathophysiological Tangles Between Allergy and Autoimmunity: Deconstructing an Old Dichotomic Paradigm.

Clin Rev Allergy Immunol. 2025-2-11

本文引用的文献

[1]
Bruton's Tyrosine Kinase Inhibitors: Recent Updates.

Int J Mol Sci. 2024-2-12

[2]
BTK signaling-a crucial link in the pathophysiology of chronic spontaneous urticaria.

J Allergy Clin Immunol. 2024-5

[3]
Cardiovascular Toxicities of BTK Inhibitors in Chronic Lymphocytic Leukemia: State-of-the-Art Review.

JACC CardioOncol. 2023-10-17

[4]
Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks.

J Allergy Clin Immunol. 2024-2

[5]
Pirtobrutinib: First Non-covalent Tyrosine Kinase Inhibitor for Treating Relapsed or Refractory Mantle Cell Lymphoma in Adults.

Curr Med Chem. 2024

[6]
Combined analysis of the impact of second-generation BTK inhibitors on patient outcomes.

Leuk Lymphoma. 2023-12

[7]
Interruption of BTK inhibitor improves response to SARS-CoV-2 booster vaccination in patients with CLL.

Leuk Lymphoma. 2023-12

[8]
Infectious complications among patients receiving ibrutinib for the treatment of hematological malignancies.

Am J Health Syst Pharm. 2024-2-8

[9]
Antibody response to SARS-CoV-2 vaccines in patients with relapsing multiple sclerosis treated with evobrutinib: A Bruton's tyrosine kinase inhibitor.

Mult Scler. 2023-10

[10]
Diagnosis and Management of Cardiovascular Effects of Bruton's Tyrosine Kinase Inhibitors.

Curr Cardiol Rep. 2023-9

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