布鲁顿酪氨酸激酶抑制剂治疗过敏性疾病的应用。

IF 1.9 Q3 ALLERGY Current Treatment Options in Allergy Pub Date : 2021-01-01 Epub Date: 2021-04-16 DOI:10.1007/s40521-021-00286-y
Melanie C Dispenza
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引用次数: 12

摘要

综述目的:研究表明,布鲁顿酪氨酸激酶(BTKis)抑制剂,目前已被fda批准用于治疗B细胞恶性肿瘤,可以通过广泛抑制人肥大细胞和嗜碱性细胞中的FcεRI信号通路来预防ige介导的反应。本综述将总结支持这些药物作为各种过敏性疾病新疗法的最新数据。最新发现:最近的研究表明,BTKis可以阻止原代人肥大细胞和嗜碱性细胞中ige介导的脱颗粒和细胞因子的产生。口服两剂第二代BTKi阿卡拉布替尼可以完全预防人源化小鼠的中度被动全身过敏反应,甚至可以防止严重过敏反应期间的死亡。此外,两个剂量的伊鲁替尼可以减少或消除过敏受试者对食物和空气过敏原的皮肤点刺试验反应。正在开发的BTKis在慢性荨麻疹的临床试验中也显示出疗效。与其他针对IgE的治疗方法(如omalizumab)不同,BTKis似乎具有快速起效和短暂作用,使其成为间歇性使用以预防急性反应(如IgE介导的过敏反应)的理想候选药物。总结:这些研究表明BTKis可能能够预防ige介导的过敏反应,为未来在食物过敏和荨麻疹中的试验铺平道路。
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The Use of Bruton's Tyrosine Kinase Inhibitors to Treat Allergic Disorders.

Purpose of review: Studies show that inhibitors of Bruton's tyrosine kinase (BTKis), currently FDA-approved for the treatment of B cell malignancies, can prevent IgE-mediated reactions through broad inhibition of the FcεRI signaling pathway in human mast cells and basophils. This review will summarize recent data supporting the use of these drugs as novel therapies in various allergic disorders.

Recent findings: Recent studies have shown that BTKis can prevent IgE-mediated degranulation and cytokine production in primary human mast cells and basophils. Two oral doses of the second-generation BTKi acalabrutinib can completely prevent moderate passive systemic anaphylaxis in humanized mice and even protect against death during severe anaphylaxis. Furthermore, two doses of ibrutinib can reduce or eliminate skin prick test responses to foods and aeroallergens in allergic subjects. BTKis in development also show efficacy in clinical trials for chronic urticaria. Unlike other therapies targeting IgE, such as omalizumab, BTKis appear to have rapid onset and transient effects, making them ideal candidates for intermittent use to prevent acute reactions such as IgE-mediated anaphylaxis.

Summary: These studies suggest that BTKis may be capable of preventing IgE-mediated anaphylaxis, paving the way for future trials in food allergy and urticaria.

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来源期刊
Current Treatment Options in Allergy
Current Treatment Options in Allergy Medicine-Medicine (miscellaneous)
CiteScore
2.50
自引率
0.00%
发文量
25
期刊介绍: Current Treatment Options in Allergy will focus on the latest advances in the treatment of allergic disorders.  Designed for physicians, this journal offers expert reviews on the management of skin allergies, venom allergies, rhinitis, asthma, food allergies, drug allergies, atopic dermatitis, allergy prevention, and anaphylaxis.Articles cover a range of established and emerging treatment options.  We accomplish this by having experts present the latest research, assess the efficacy of available treatment options, and discuss special considerations.  We ensure that the journal content includes current, emerging research and suggest articles of special interest.
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