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单克隆抗体治疗哮喘和伴有嗜酸性粒细胞炎症的慢性阻塞性肺疾病。

Monoclonal antibody therapy for the treatment of asthma and chronic obstructive pulmonary disease with eosinophilic inflammation.

机构信息

MedImmune Ltd., Cambridge, UK.

MedImmune LLC, Gaithersburg, MD, USA.

出版信息

Pharmacol Ther. 2017 Jan;169:57-77. doi: 10.1016/j.pharmthera.2016.10.016. Epub 2016 Oct 20.

DOI:10.1016/j.pharmthera.2016.10.016
PMID:27773786
Abstract

Eosinophils have been linked with asthma for more than a century, but their role has been unclear. This review discusses the roles of eosinophils in asthma and chronic obstructive pulmonary disease (COPD) and describes therapeutic antibodies that affect eosinophilia. The aims of pharmacologic treatments for pulmonary conditions are to reduce symptoms, slow decline or improve lung function, and reduce the frequency and severity of exacerbations. Inhaled corticosteroids (ICS) are important in managing symptoms and exacerbations in asthma and COPD. However, control with these agents is often suboptimal, especially for patients with severe disease. Recently, new biologics that target eosinophilic inflammation, used as adjunctive therapy to corticosteroids, have proven beneficial and support a pivotal role for eosinophils in the pathology of asthma. Nucala® (mepolizumab; anti-interleukin [IL]-5) and Cinquair® (reslizumab; anti-IL-5), the second and third biologics approved, respectively, for the treatment of asthma, exemplifies these new treatment options. Emerging evidence suggests that eosinophils may contribute to exacerbations and possibly to lung function decline for a subset of patients with COPD. Here we describe the pharmacology of therapeutic antibodies inhibiting IL-5 or targeting the IL-5 receptor, as well as other cytokines contributing to eosinophilic inflammation. We discuss their roles as adjuncts to conventional therapeutic approaches, especially ICS therapy, when disease is suboptimally controlled. These agents have achieved a place in the therapeutic armamentarium for asthma and COPD and will deepen our understanding of the pathogenic role of eosinophils.

摘要

嗜酸性粒细胞与哮喘的关联已有一个多世纪,但它们的作用仍不清楚。本文讨论了嗜酸性粒细胞在哮喘和慢性阻塞性肺疾病(COPD)中的作用,并描述了影响嗜酸性粒细胞增多的治疗性抗体。肺部疾病的药物治疗目的是减轻症状、减缓或改善肺功能,并减少恶化的频率和严重程度。吸入性皮质类固醇(ICS)在哮喘和 COPD 的症状和恶化管理中非常重要。然而,这些药物的控制效果往往并不理想,尤其是对于严重疾病的患者。最近,靶向嗜酸性粒细胞炎症的新型生物制剂作为皮质类固醇的辅助治疗已被证明是有益的,并支持嗜酸性粒细胞在哮喘病理中的关键作用。Nucala®(美泊利珠单抗;抗白细胞介素[IL]-5)和 Cinquair®(瑞利珠单抗;抗 IL-5),分别是第二种和第三种批准用于哮喘治疗的生物制剂,就是这些新治疗选择的范例。新出现的证据表明,嗜酸性粒细胞可能会导致一部分 COPD 患者恶化,甚至可能导致肺功能下降。本文描述了抑制 IL-5 或靶向 IL-5 受体的治疗性抗体以及其他导致嗜酸性粒细胞炎症的细胞因子的药理学。我们讨论了它们作为传统治疗方法(尤其是 ICS 治疗)的辅助手段的作用,尤其是在疾病控制不佳时。这些药物已成为哮喘和 COPD 治疗武器库中的一部分,将加深我们对嗜酸性粒细胞致病作用的理解。

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