Department of Clinical and Experimental Medicine, University of Catania, Catania (CT), Italy.
Department of Respiratory Medicine, Royal Brompton & Harefield Hospital Foundation Trust, Harefield Hospital, Hill End Road, Harefield, UK.
Ther Adv Respir Dis. 2018 Jan-Dec;12:1753466618808490. doi: 10.1177/1753466618808490.
Asthma is a chronic inflammatory condition involving the airways with varying pathophysiological mechanisms, clinical symptoms and outcomes, generally controlled by conventional therapies including inhaled corticosteroids and long-acting β agonists. However, these therapies are unable to successfully control symptoms in about 5-10% of severe asthma patients. Atopic asthma, characterized by high immunoglobulin (Ig)E or eosinophilia, represents about 50% of asthmatic patients. Interleukin (IL)-5 is the main cytokine responsible of activation of eosinophils, hence therapeutic strategies have been investigated and developed for clinical use. Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in asthma patients. Despite these biologics having been approved for stratified severe asthma patients that remain uncontrolled with high doses of conventional therapy, a number of patients may be eligible for more than one biologic. Presently, the lack of head-to-head studies comparing the biological agents among themselves and with conventional therapy make the choice of optimal therapy for each patient a challenge for clinicians. Moreover, discontinuation of these treatments, implications for efficacy or adverse events, in particular in long-term treatment, and needs for useful biomarkers are still matters of debate. In this review we evaluate to date, the evidence on mepolizumab that seems to demonstrate it is a well-tolerated and efficacious regimen for use in severe eosinophilic asthma, though more studies are still required.
哮喘是一种气道慢性炎症性疾病，其病理生理机制、临床症状和结局各不相同，通常通过常规治疗（包括吸入皮质类固醇和长效β激动剂）来控制。然而，这些治疗方法无法成功控制约 5-10%的重度哮喘患者的症状。特应性哮喘的特点是高免疫球蛋白（Ig）E 或嗜酸性粒细胞增多，约占哮喘患者的 50%。白细胞介素（IL）-5 是激活嗜酸性粒细胞的主要细胞因子，因此已经研究并开发了治疗策略用于临床应用。针对 IL-5 及其受体的生物制剂（首先是美泊利珠单抗，随后是瑞利珠单抗和本那利珠单抗）已被最近批准并用作重度嗜酸性粒细胞性哮喘的附加治疗方法，导致循环嗜酸性粒细胞计数减少、肺功能改善和哮喘患者恶化减少。尽管这些生物制剂已被批准用于用高剂量常规治疗仍无法控制的分层重度哮喘患者，但许多患者可能有资格使用不止一种生物制剂。目前，缺乏比较这些生物制剂彼此之间以及与常规治疗的头对头研究，使得为每个患者选择最佳治疗方案成为临床医生的一个挑战。此外，这些治疗的停药、疗效或不良反应的影响，特别是在长期治疗中，以及对有用生物标志物的需求，仍然存在争议。在这篇综述中，我们评估了迄今为止关于美泊利珠单抗的证据，该证据似乎表明它是一种治疗重度嗜酸性粒细胞性哮喘的耐受性好且有效的方案，但仍需要更多的研究。
