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研究性抗 IL-13 哮喘治疗药物:2023 年更新。

Investigational anti IL-13 asthma treatments: a 2023 update.

机构信息

Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.

Division of Respiratory Medicine, University Hospital Tor Vergata, Rome, Italy.

出版信息

Expert Opin Investig Drugs. 2023 May;32(5):373-386. doi: 10.1080/13543784.2023.2215425. Epub 2023 May 18.

Abstract

INTRODUCTION

IL-13 is a pleiotropic type 2 cytokine important in the pathogenesis of asthma and other eosinophilic disorders.

AREAS COVERED

Different attempts to directly neutralize IL-13 or block its receptors and the possible impact that these approaches may have in the treatment of asthma.

EXPERT OPINION

Collectively, specific anti-IL-13 agents are ineffective in treating severe asthma. Lebrikizumab and tralokinumab, the two most widely studied anti-IL-13 monoclonal antibodies, did not show any statistically significant improvement in quality of life or reduction in asthma exacerbation and/or symptoms in phase III studies. Consequently, their clinical development for the treatment of patients with asthma has been halted indefinitely. Other attempts to block or, at least limit, the impact of IL-13 in asthma, such as the use of protein-protein interaction modulators, kinase inhibitors, bispecific antibodies, or IL-13 peptide vaccines, are largely still in the preclinical stage of development, and it is difficult to predict whether they will reach clinical development. Nevertheless, since IL-13 directly affects airway contractility and is critical for mucus production and remodeling, and airflow limitation and mucus hypersecretion are commonly treatable features in asthma, we suggest including an anti-IL-13 drug before GINA step 5.

摘要

简介

IL-13 是一种多效性的 2 型细胞因子,在哮喘和其他嗜酸性疾病的发病机制中起重要作用。

涵盖领域

不同尝试直接中和 IL-13 或阻断其受体,以及这些方法可能对哮喘治疗产生的影响。

专家意见

总的来说,针对 IL-13 的特异性单克隆抗体在治疗严重哮喘方面无效。在 III 期研究中,两种研究最广泛的抗 IL-13 单克隆抗体 lebrikizumab 和 tralokinumab 均未显示在生活质量或哮喘恶化和/或症状方面有任何统计学意义的改善。因此,它们的临床开发已无限期停止用于治疗哮喘患者。其他试图阻断或至少限制 IL-13 在哮喘中的作用的方法,例如使用蛋白-蛋白相互作用调节剂、激酶抑制剂、双特异性抗体或 IL-13 肽疫苗,在很大程度上仍处于临床前开发阶段,很难预测它们是否会进入临床开发。尽管如此,由于 IL-13 直接影响气道收缩性,并且对粘液产生和重塑至关重要,而气流受限和粘液高分泌是哮喘常见的可治疗特征,我们建议在 GINA 第 5 步之前使用抗 IL-13 药物。

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