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儿童和青少年重度哮喘的靶向治疗:现状和未来展望。

Targeted Therapy for Severe Asthma in Children and Adolescents: Current and Future Perspectives.

机构信息

Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, viale Golgi 19, 27100, Pavia, Italy.

Unit of Pediatric Genetics and Immunology, Department of Pediatrics, University of Messina, Messina, Italy.

出版信息

Paediatr Drugs. 2019 Aug;21(4):215-237. doi: 10.1007/s40272-019-00345-7.

Abstract

Severe asthma in children remains a significant issue. It places a heavy burden on affected individuals and society as a whole in terms of high morbidity, mortality, consumption of healthcare resources, and side effects from high-dose corticosteroid therapy. New, targeted biologic therapies for asthma have emerged as effective add-on options, complementing our expanding understanding of asthma phenotypes/endotypes and the underlying immunopathology of the disease spectrum. They include omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. Omalizumab represents the first available therapeutic option for allergic asthma in patients as young as 6 years of age. Its efficacy and safety have been established by several randomized controlled trials specifically conducted in pediatric patients, leading to its final registration > 10 years ago. Three new interleukin (IL)-5 targeted agents, mepolizumab, reslizumab, and benralizumab, have been approved for the treatment of severe eosinophilic asthma starting from 6 years of age, and varying by country. More recently, dupilumab, a targeted agent against the IL-4 receptor α-chain, was approved for patients ≥12 years of age in the United States after pivotal trials were completed. The late-stage clinical testing of these targeted agents has mostly involved patients aged 12 years and up, and the application of those data to younger children can be inappropriate and carry risk. The efficacy and safety of these newer biologics in children should be supported by adequate research within this targeted age group. In this review, we will present the most recent evidence on these five biological therapies for severe asthma and will discuss dosage and administration, their efficacy, safety, and future prospects, with a focus on the pediatric age group, defined as age < 18 years.

摘要

儿童严重哮喘仍然是一个重大问题。它在发病率、死亡率、医疗资源消耗以及大剂量皮质类固醇治疗的副作用方面给受影响的个人和整个社会带来了沉重的负担。针对哮喘的新型靶向生物疗法已成为有效的附加选择,补充了我们对哮喘表型/内型和疾病谱潜在免疫病理学的不断扩大的认识。这些疗法包括奥马珠单抗、美泊利单抗、瑞利珠单抗、贝那利珠单抗和度普利尤单抗。奥马珠单抗是 6 岁及以上过敏性哮喘患者的首个可用治疗选择。几项专门在儿科患者中进行的随机对照试验已经证实了其疗效和安全性,这导致其在 10 多年前最终注册。三种新的白细胞介素 (IL)-5 靶向药物,美泊利单抗、瑞利珠单抗和贝那利珠单抗,已获准用于治疗 6 岁及以上的严重嗜酸性粒细胞性哮喘,具体批准情况因国家而异。最近,针对白细胞介素-4 受体 α 链的靶向药物度普利尤单抗在美国被批准用于≥12 岁的患者,此前已完成关键试验。这些靶向药物的后期临床测试主要涉及 12 岁及以上的患者,将这些数据应用于年龄较小的儿童可能不合适,并存在风险。这些新型生物制剂在儿童中的疗效和安全性应得到该目标年龄段内充分研究的支持。在这篇综述中,我们将介绍这五种严重哮喘生物疗法的最新证据,并将讨论剂量和管理、疗效、安全性和未来前景,重点关注儿科年龄组(定义为年龄<18 岁)。

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