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重度嗜酸性粒细胞性哮喘:从白细胞介素-5的致病作用到美泊利珠单抗的治疗作用

Severe eosinophilic asthma: from the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab.

作者信息

Pelaia Corrado, Vatrella Alessandro, Busceti Maria Teresa, Gallelli Luca, Terracciano Rosa, Savino Rocco, Pelaia Girolamo

机构信息

Department of Medical and Surgical Sciences, Section of Respiratory Diseases, University "Magna Græcia" of Catanzaro, Catanzaro.

Department of Medicine, Surgery and Dentistry, Section of Respiratory Diseases, University of Salerno, Salerno.

出版信息

Drug Des Devel Ther. 2017 Oct 30;11:3137-3144. doi: 10.2147/DDDT.S150656. eCollection 2017.

Abstract

Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that has been recently approved as an add-on biological treatment for severe eosinophilic asthma, by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Moreover, mepolizumab is also currently included within the step 5 of the Global Initiative for Asthma guidelines, as an add-on therapy for severe uncontrolled asthma. The relevant therapeutic benefits detectable in patients with refractory eosinophilic asthma receiving mepolizumab depend on the pivotal pathogenic role played by IL-5 in these subjects. Indeed, IL-5 is the key cytokine responsible for maturation, activation, proliferation, and survival of eosinophils. Therefore, IL-5 represents a strategic molecular target for anti-eosinophilic treatments. By selectively inhibiting the biological actions of IL-5, mepolizumab provides a valuable therapeutic option for patients with severe eosinophilic asthma, refractory to standard treatments including inhaled and even systemic corticosteroids. In particular, the very important advantages linked to the use of mepolizumab in these difficult-to-treat asthmatic individuals have been well documented by several different trials performed worldwide.

摘要

美泊利珠单抗是一种抗白细胞介素-5(IL-5)人源化单克隆抗体,最近已获得美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)批准,作为重度嗜酸性粒细胞性哮喘的附加生物治疗药物。此外,美泊利珠单抗目前也被纳入全球哮喘防治创议指南的第5步,作为重度未控制哮喘的附加治疗药物。在接受美泊利珠单抗治疗的难治性嗜酸性粒细胞性哮喘患者中可检测到的相关治疗益处,取决于IL-5在这些患者中所起的关键致病作用。事实上,IL-5是负责嗜酸性粒细胞成熟、激活、增殖和存活的关键细胞因子。因此,IL-5是抗嗜酸性粒细胞治疗的一个战略分子靶点。通过选择性抑制IL-5的生物学作用,美泊利珠单抗为重度嗜酸性粒细胞性哮喘患者提供了一种有价值的治疗选择,这些患者对包括吸入甚至全身用糖皮质激素在内的标准治疗无效。特别是,在全球范围内进行的多项不同试验已充分证明了在这些难治性哮喘患者中使用美泊利珠单抗的非常重要的优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e479/5669784/94680d3909c7/dddt-11-3137Fig1.jpg

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