Paton D M
University of Auckland, Auckland, New Zealand.
Drugs Today (Barc). 2016 Jun;52(6):323-9. doi: 10.1358/dot.2016.52.6.2510261.
The starting point for this drug was the growing realization that eosinophils appeared to be associated with a severe form of asthma in which patients were subject to exacerbations of their condition that could not be adequately managed using inhaled and/or oral corticosteroids. Studies of the pathophysiology of eosinophils revealed that they produce many bioactive compounds that contribute to the pathophysiology of a number of diseases including asthma. Interleukin-5 (IL-5) in particular is an important factor in some forms of severe asthma. A rat antibody to IL-5 (39D10) was humanized producing the product now know as reslizumab. However, initial studies of this antibody in patients with asthma were unsuccessful. It was only when the importance of the eosinophilic asthma endotype was recognized that reslizumab was found to indeed reduce the severity and exacerbations of asthma in patients who were inadequately treated by inhaled and/ or oral corticosteroids. These studies have determined that reslizumab is a valuable drug for the management of such patients provided that they have an eosinophil count of > 400 cells/mcL. Because a very small percentage of patients receiving reslizumab may experience anaphylaxis, reslizumab must be only given in a facility with adequate facilities and by a health professional trained in the management of anaphylaxis.
这种药物的研发起点是,人们越来越意识到嗜酸性粒细胞似乎与一种严重的哮喘形式有关,在这种哮喘中,患者的病情会加重,而使用吸入性和/或口服皮质类固醇无法充分控制病情。对嗜酸性粒细胞病理生理学的研究表明,它们会产生许多生物活性化合物,这些化合物会导致包括哮喘在内的多种疾病的病理生理过程。特别是白细胞介素-5(IL-5)在某些严重哮喘形式中是一个重要因素。一种针对IL-5的大鼠抗体(39D10)被人源化,产生了现在所知的瑞利珠单抗。然而,这种抗体在哮喘患者中的初步研究并不成功。直到嗜酸性粒细胞性哮喘内型的重要性被认识到,才发现瑞利珠单抗确实能降低吸入性和/或口服皮质类固醇治疗效果不佳的患者哮喘的严重程度和发作频率。这些研究已经确定,瑞利珠单抗对于管理此类患者是一种有价值的药物,前提是他们的嗜酸性粒细胞计数>400个细胞/微升。由于接受瑞利珠单抗治疗的患者中只有非常小的比例可能会发生过敏反应,瑞利珠单抗必须仅在具备适当设施的机构中,由接受过过敏反应管理培训的卫生专业人员给药。