抗细胞因子生物制剂治疗成人哮喘

Elliot Israel, Michael E Wechsler, David J Jackson, Wendy C Moore
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摘要

估计有3-10%的哮喘患者无法通过目前可用的吸入疗法达到完全控制。在这些患者中,很大一部分哮喘可全部或部分由2型(T2)炎症引起,这通常是由粘膜表面刺激的免疫反应引起的。针对T2炎症过程的单克隆抗体的引入为这一人群提供了重要的选择。在过去的十年中,已经引入了五种抗细胞因子生物制剂(ACBs)来阻断特定的T2炎症细胞因子。三种生物制剂,mepolizumab, reslizumab和benralizumab,抑制IL-5或IL-5受体途径;dupilumab通过其对IL-4受体α的活性阻断IL-4和IL-13;而tezepelumab可以阻止胸腺基质淋巴生成素细胞因子级联产生的激活。这些药物可减少哮喘加重,改善有哮喘加重史和T2炎症证据的个体的肺功能和患者报告的哮喘生活质量。一些还允许口服皮质类固醇减少或消除患者依赖这些治疗来控制哮喘。ACBs的作用随T2炎症程度的不同而不同,最容易通过血液嗜酸性粒细胞计数和呼出的一氧化氮来评估。在这些生物标记物和严重哮喘患者表型特征的指导下使用acb,可以采用个性化的药物方法,增加改善的可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti-cytokine biologics for asthma in adults
An estimated 3–10% of patients with asthma are unable to reach full control with currently available inhaled therapies. In a large proportion of these patients, asthma can be driven in whole or in part by type 2 (T2) inflammation, which is usually initiated by an immunological response to stimulation at mucosal surfaces. The introduction of monoclonal antibodies, which target T2 inflammatory processes, provides important options for this population. In the past decade, five anticytokine biologics (ACBs) that block specific T2 inflammatory cytokines have been introduced. Three biologics, mepolizumab, reslizumab, and benralizumab, inhibit the IL-5 or IL-5 receptor pathway; dupilumab blocks IL-4 and IL-13 through its activity on the IL-4 receptor-alpha; and tezepelumab prevents activation of the thymic stromal lymphopoietin cytokine production cascade. These drugs reduce exacerbations and improve lung function and patient-reported asthma quality of life in individuals with a history of asthma exacerbations and evidence of T2 inflammation. Some also allow oral corticosteroid reduction or elimination in patients dependent on these therapies for asthma control. The effect of ACBs varies by the degree of T2 inflammation, which is most easily assessed by blood eosinophil counts and exhaled nitric oxide. The use of ACBs guided by these biomarkers and phenotypic characteristics of patients with severe asthma allows a personalised medicine approach that increases the likelihood of improvement.
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