1 Division of Pulmonary and Critical Care, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; and.
2 Division of Respirology, Department of Medicine, St. Joseph's Healthcare Hamilton, McMaster University, Hamilton, Ontario, Canada.
Am J Respir Crit Care Med. 2019 Feb 15;199(4):433-445. doi: 10.1164/rccm.201810-1944CI.
Patients with severe uncontrolled asthma have disproportionally high morbidity and healthcare utilization as compared with their peers with well-controlled disease. Although treatment options for these patients were previously limited, with unacceptable side effects, the emergence of biologic therapies for the treatment of asthma has provided promising targeted therapy for these patients. Biologic therapies target specific inflammatory pathways involved in the pathogenesis of asthma, particularly in patients with an endotype driven by type 2 (T2) inflammation. In addition to anti-IgE therapy that has improved outcomes in allergic asthma for more than a decade, three anti-IL-5 biologics and one anti-IL-4R biologic have recently emerged as promising treatments for T2 asthma. These targeted therapies have been shown to reduce asthma exacerbations, improve lung function, reduce oral corticosteroid use, and improve quality of life in appropriately selected patients. In addition to the currently approved biologic agents, several biologics targeting upstream inflammatory mediators are in clinical trials, with possible approval on the horizon. This article reviews the mechanism of action, indications, expected benefits, and side effects of each of the currently approved biologics for severe uncontrolled asthma and discusses promising therapeutic targets for the future.
与病情控制良好的患者相比,严重未控制的哮喘患者的发病率和医疗保健利用率不成比例地高。尽管这些患者的治疗选择以前受到限制,存在不可接受的副作用,但生物疗法的出现为这些患者提供了有前途的靶向治疗。生物疗法针对哮喘发病机制中涉及的特定炎症途径,特别是在 2 型(T2)炎症驱动的表型患者中。除了抗 IgE 疗法在过敏性哮喘中改善了十多年的预后外,三种抗 IL-5 生物制剂和一种抗 IL-4R 生物制剂最近已成为 T2 哮喘的有前途的治疗方法。这些靶向疗法已被证明可减少哮喘恶化、改善肺功能、减少口服皮质类固醇的使用,并改善适当选择的患者的生活质量。除了目前批准的生物制剂外,几种针对上游炎症介质的生物制剂正在临床试验中,可能即将获得批准。本文综述了每种已批准用于严重未控制哮喘的生物制剂的作用机制、适应证、预期益处和副作用,并讨论了未来有前途的治疗靶点。