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Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience

机译:美泊利珠单抗治疗成人严重嗜酸性粒细胞性哮喘:最新证据和实践经验

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摘要

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 β2 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.
机译:哮喘是一种慢性炎症,涉及气道,具有各种病理生理机制,临床症状和结局,通常由包括吸入糖皮质激素和长效β2激动剂在内的常规疗法控制。但是,这些疗法无法成功控制约5-10%的严重哮喘患者的症状。以高免疫球蛋白(Ig)E或嗜酸性粒细胞增多为特征的特应性哮喘约占哮喘患者的50%。白介素(IL)-5是负责激活嗜酸性粒细胞的主要细胞因子,因此已经研究和开发了治疗策略以用于临床。最近已批准了针对IL-5及其受体(首先是美泊珠单抗,随后是瑞利珠单抗和贝那利珠单抗)的生物制剂,并将其用作严重嗜酸性粒细胞性哮喘的附加疗法,从而导致循环中嗜酸性粒细胞减少,肺功能改善和恶化减少哮喘患者。尽管这些生物制剂已被批准用于分层的重度哮喘患者,这些患者仍无法通过高剂量的常规疗法加以控制,但仍有许多患者有资格使用一种以上的生物制剂。目前,缺乏将生物制剂之间以及与传统疗法进行比较的直接研究,使得为每个患者选择最佳疗法对临床医生来说是一个挑战。而且,这些治疗的中断,对功效或不良事件的影响,特别是在长期治疗中,以及对有用的生物标志物的需求仍然是争论的问题。迄今为止,在本综述中,我们评估了美泊利单抗上的证据似乎表明,对于严重的嗜酸性粒细胞性哮喘,它是一种耐受良好且有效的方案,尽管仍需要进行更多的研究。

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