Redefining Approaches to Asthma: Developing Targeted Biologic Therapies
Redefining Approaches to Asthma: Developing Targeted Biologic Therapies
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DOI：
10.1016/b978-0-12-404717-4.00001-9
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发表时间：
2013-01-01
期刊：
影响因子：
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通讯作者：
Matthews, John G.
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文献类型：
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作者：
Arron, Joseph R.;Scheerens, Heleen;Matthews, John G.
哮喘是一种与2型气道炎症典型相关的慢性呼吸系统疾病，其特征在于嗜酸性粒细胞、免疫球蛋白E和细胞因子（包括白细胞介素（IL）4、IL 5、IL 9和IL 13以及肿瘤坏死因子（TNF）α）水平升高。然而，越来越多的证据表明，人类哮喘在气道炎症的性质和强度方面存在相当大的异质性。虽然许多哮喘患者通过标准治疗（如β 2-肾上腺素能受体激动剂和吸入性皮质类固醇）实现了可接受的症状控制，但少数患者尽管接受了最大标准治疗仍有症状，构成了显著未满足的医疗需求。越来越多的哮喘临床开发中的研究性治疗药物是特异性靶向2型气道炎症介质的生物疗法。在本章中，我们考虑了哮喘治疗靶点的生物学功能和针对这些靶点的生物制剂的临床试验数据。我们讨论了最近的临床试验结果的药物开发的四个关键组成部分：目标选择，分子选择，结果选择和患者选择，特别注意的生物标志物在哮喘临床开发中的新兴作用。
Asthma is a chronic respiratory disorder canonically associated with type 2 airway inflammation as characterized by elevated levels of eosinophils, immunoglobulin E, and cytokines including interleukin (IL) 4, IL5, IL9, and IL13 and tumor necrosis factor (TNF) alpha. However, mounting evidence has shown that considerable heterogeneity exists in human asthma in terms of the nature and intensity of airway inflammation. While many asthma patients achieve acceptable control of symptoms with standard-of-care therapies such as beta(2)-adrenergic agonists and inhaled corticosteroids, a minority remains symptomatic despite maximal standard-of-care therapy and constitutes a significant unmet medical need. A growing number of investigational therapeutics under clinical development for asthma are biologic therapies that specifically target mediators of type 2 airway inflammation. In this chapter, we consider the biological functions of therapeutic targets in asthma and data from clinical trials of biologic agents directed against these targets. We discuss recent clinical trial results in terms of four key components of drug development: target selection, molecule selection, outcome selection, and patient selection, with particular attention paid to the emerging role of biomarkers in clinical development for asthma.