Hilvering Bart, Xue Luzheng, Pavord Ian D
Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK and Department of Respiratory Medicine, Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Ther Adv Respir Dis. 2015 Aug;9(4):135-45. doi: 10.1177/1753465815581279. Epub 2015 Apr 21.
Two recent phase III trials in patients with severe eosinophilic asthma have shown that anti-interleukin 5 (IL-5) therapy with mepolizumab reduces the frequency of asthma attacks, improves symptoms and allows patients to reduce oral glucocorticoid use without loss of control of asthma. An earlier large 616 patient Dose Ranging Efficacy And safety with Mepolizumab in severe asthma (DREAM) study had shown that the only variables associated with treatment efficacy were a prior history of asthma attacks and the peripheral blood eosinophil count. The link between blood eosinophil counts and treatment efficacy is biologically obvious given that IL-5 has a pivotal role in eosinophil production, proliferation and chemotaxis. It is also clinically relevant as the blood eosinophil count is routinely measured and thus readily available in patients with asthma. Recognition of the link between airway or blood eosinophilia and treatment response was also important in the clinical testing of the alternative IL-5 blocker, such as reslizumab, which is currently being evaluated in a phase III randomized controlled trial (RCT) after having shown to improve lung function, improve symptom score and reduce sputum eosinophilia in a smaller phase IIb study. In addition, benralizumab, an IL-5α receptor blocker, has shown good effects in a phase IIb RCT with patients with severe asthma that had sputum eosinophilia and more recently in a phase IIa trial with patients with eosinophilic chronic obstructive pulmonary disease. Therefore anti-IL-5 treatment seems generally effective in eosinophilic asthma, either assessed by blood or airway eosinophilia. This factor together with the impressive clinical efficacy and good safety profile make anti-IL-5 (mepolizumab, reslizumab) and benralizumab (anti-IL-5 receptor α) very promising drugs for the treatment of patients with severe eosinophilic asthma, a subgroup that is in desperate need of better treatments.
最近两项针对重度嗜酸性粒细胞性哮喘患者的III期试验表明,使用美泊利珠单抗进行抗白细胞介素5(IL-5)治疗可降低哮喘发作频率、改善症状,并使患者能够减少口服糖皮质激素的使用,同时不会失去对哮喘的控制。一项早期纳入616例患者的美泊利珠单抗治疗重度哮喘的剂量范围疗效和安全性(DREAM)大型研究表明,与治疗疗效相关的唯一变量是既往哮喘发作史和外周血嗜酸性粒细胞计数。鉴于IL-5在嗜酸性粒细胞的产生、增殖和趋化作用中起关键作用,血液嗜酸性粒细胞计数与治疗疗效之间的联系在生物学上是显而易见的。它在临床上也具有相关性,因为血液嗜酸性粒细胞计数是常规测量的,因此在哮喘患者中很容易获得。认识到气道或血液嗜酸性粒细胞增多与治疗反应之间的联系在替代IL-5阻滞剂(如瑞利珠单抗)的临床测试中也很重要,瑞利珠单抗在一项规模较小的IIb期研究中显示可改善肺功能、改善症状评分并减少痰液嗜酸性粒细胞增多,目前正在进行III期随机对照试验(RCT)评估。此外,IL-5α受体阻滞剂贝那利珠单抗在一项针对有痰液嗜酸性粒细胞增多的重度哮喘患者的IIb期RCT中显示出良好效果,最近在一项针对嗜酸性粒细胞性慢性阻塞性肺疾病患者的IIa期试验中也有良好表现。因此,无论是通过血液还是气道嗜酸性粒细胞增多来评估,抗IL-5治疗在嗜酸性粒细胞性哮喘中似乎总体有效。这一因素连同令人印象深刻的临床疗效和良好的安全性,使得抗IL-5(美泊利珠单抗、瑞利珠单抗)和贝那利珠单抗(抗IL-5受体α)成为治疗重度嗜酸性粒细胞性哮喘患者非常有前景的药物,这一亚组患者迫切需要更好的治疗方法。