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用于嗜酸性粒细胞性哮喘的生物疗法。

Biological therapies for eosinophilic asthma.

机构信息

a Division of Allergy and Immunology, Department of Internal Medicine , University of South Florida Morsani College of Medicine and James A. Haley Veterans' Affairs Hospital , Tampa , FL , USA.

出版信息

Expert Opin Biol Ther. 2018 Jul;18(7):747-754. doi: 10.1080/14712598.2018.1492540. Epub 2018 Jul 4.

DOI:10.1080/14712598.2018.1492540
PMID:29938543
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6317519/
Abstract

INTRODUCTION

Severe uncontrolled asthma is by definition refractory to traditional therapies or can be controlled only with therapies that have intolerable side effects. Monoclonal antibodies that target interleukin (IL)-5/IL-5Rα, IgE, and IL-4Rα have shown favorable results in clinical trials, including reductions in asthma exacerbations and other important clinical outcomes. These biological agents offer treatment alternatives to patients with uncontrolled severe eosinophilic asthma.

AREAS COVERED

This article reviews how the shifting emphasis toward identifying distinct asthma phenotypes has led to the approval of biological therapies that preferentially benefit patients with severe eosinophilic asthma. The clinical trials that led to the approval of these biologic treatments are discussed in detail.

EXPERT OPINION

Biologic therapies targeting the IL-5, IgE, IL-4/IL-13 signaling pathways have been successful in clinical trials in subjects with severe eosinophilic asthma. Some of these agents have also been successful regardless of peripheral blood eosinophil counts. These treatments have shown a relatively favorable safety profile in clinical trials, although long-term safety data for some of these agents are limited. Due to the high costs associated with these medications, they should be reserved for select patients where they yield a therapeutic and pharmacoeconomic advantage.

摘要

简介

重度未控制哮喘根据定义是对传统疗法有抵抗性的,或者只能通过具有不可耐受副作用的疗法来控制。靶向白细胞介素 (IL)-5/IL-5Rα、IgE 和 IL-4Rα 的单克隆抗体在临床试验中显示出了良好的效果,包括减少哮喘恶化和其他重要的临床结局。这些生物制剂为未控制的重度嗜酸性粒细胞性哮喘患者提供了治疗选择。

涵盖的领域

本文回顾了如何将重点转移到识别不同的哮喘表型,从而导致批准了对重度嗜酸性粒细胞性哮喘患者有优先获益的生物疗法。详细讨论了促成这些生物治疗批准的临床试验。

专家意见

针对 IL-5、IgE、IL-4/IL-13 信号通路的生物疗法在重度嗜酸性粒细胞性哮喘患者的临床试验中取得了成功。其中一些药物在无论外周血嗜酸性粒细胞计数如何的情况下也取得了成功。这些治疗方法在临床试验中显示出了相对良好的安全性概况,尽管其中一些药物的长期安全性数据有限。由于这些药物相关的费用高昂,它们应该保留给那些在治疗和药物经济学方面具有优势的特定患者。

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本文引用的文献

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Reslizumab in the treatment of severe eosinophilic asthma: an update.瑞利珠单抗治疗重度嗜酸性粒细胞性哮喘:最新进展
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Safety of humanized monoclonal antibodies against IL-5 in asthma: focus on reslizumab.抗白细胞介素-5人源化单克隆抗体在哮喘治疗中的安全性:聚焦于瑞利珠单抗
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Long-term Safety and Efficacy of Reslizumab in Patients with Eosinophilic Asthma.瑞利珠单抗治疗嗜酸性粒细胞性哮喘患者的长期安全性和疗效。
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Dupilumab for the treatment of asthma.度普利尤单抗用于治疗哮喘。
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Overlapping Effects of New Monoclonal Antibodies for Severe Asthma.新单克隆抗体治疗严重哮喘的重叠作用。
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Anti-IL5 therapies for asthma.用于哮喘的抗白细胞介素-5疗法。
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Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab.体重调整的静脉注射瑞利珠单抗治疗对固定剂量皮下美泊利珠单抗应答不足的重症哮喘。
Am J Respir Crit Care Med. 2018 Jan 1;197(1):38-46. doi: 10.1164/rccm.201707-1323OC.
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Response to omalizumab using patient enrichment criteria from trials of novel biologics in asthma.根据哮喘新型生物制剂试验中的患者富集标准,对奥马珠单抗的反应。
Allergy. 2018 Feb;73(2):490-497. doi: 10.1111/all.13302. Epub 2017 Sep 23.
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Biologic Therapy and Novel Molecular Targets of Severe Asthma.生物疗法和严重哮喘的新型分子靶点。
J Allergy Clin Immunol Pract. 2017 Jul-Aug;5(4):909-916. doi: 10.1016/j.jaip.2017.04.038.
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Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma.贝那鲁肽在重症哮喘中的糖皮质激素节省作用。
N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22.