Marseglia Gian Luigi, Licari Amelia, Tosca Maria Angela, Ciprandi Giorgio
Department of Pediatrics, Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
Pediatric Allergy Center, Istituto Giannina Gaslini, Genoa, Italy.
Pediatr Allergy Immunol Pulmonol. 2020 Dec;33(4):168-176. doi: 10.1089/ped.2020.1212. Epub 2020 Nov 13.
Severe asthma represents a significant challenge for children and adolescents. At the same time, it often places a burden on patients, caregivers, and society, mainly related to morbidity, mortality, and health care resources. In children and adolescents, severe asthma is mostly characterized by type 2 inflammation, which leads to bronchial eosinophilia that may be suppressed by corticosteroids. However, in this age group, a high dosage of inhaled corticosteroids combined with systemic corticosteroids sometimes results in unacceptable side effects, such as reduced growth velocity and reduced bone mineral density. Therefore, there is increasing and enthusiastic interest in today's biologics, including omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. There is growing evidence that they may be effective and safe add-on options for children and adolescents. In 2009, omalizumab was approved by the European Medicines Agency as the first available therapeutic option for allergic asthma in patients as young as 6 years of age, followed by a similar approval by the U.S. Food and Drug Administration in 2016. Previously, omalizumab was marketed for this indication in patients ≥ age 12. Subsequent biologics, namely mepolizumab, reslizumab, and benralizumab, are IL-5 targeted agents that are presently approved in some countries for severe eosinophilic asthma starting at 6 years of age. Dupilumab is targeted against the IL-4 receptor α-chain, and it has been approved in the United States and the European Union as an add-on maintenance therapy in patients ≥12 years of age. This review presents the most recent evidence on approved biologics for the treatment of severe asthma and discusses the unmet needs and future perspective, focusing on the pediatric and adolescent age groups.
重度哮喘对儿童和青少年来说是一项重大挑战。与此同时，它常常给患者、照料者和社会带来负担，主要涉及发病率、死亡率和医疗保健资源。在儿童和青少年中，重度哮喘大多以2型炎症为特征，这种炎症会导致支气管嗜酸性粒细胞增多，而皮质类固醇可能会抑制这种情况。然而，在这个年龄组中，高剂量吸入性皮质类固醇与全身性皮质类固醇联合使用有时会产生不可接受的副作用，如生长速度减慢和骨密度降低。因此，如今人们对生物制剂，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，越来越感兴趣且热情高涨。越来越多的证据表明，它们可能是儿童和青少年有效且安全的附加治疗选择。2009年，奥马珠单抗被欧洲药品管理局批准为6岁及以上过敏性哮喘患者的首个可用治疗选择，随后于2016年获得美国食品药品监督管理局的类似批准。此前，奥马珠单抗已在12岁及以上患者中用于这一适应症。随后的生物制剂，即美泊利单抗、瑞利珠单抗和贝那利珠单抗，是靶向白细胞介素-5的药物，目前在一些国家已被批准用于6岁及以上的重度嗜酸性粒细胞性哮喘。度普利尤单抗靶向白细胞介素-4受体α链，已在美国和欧盟被批准作为12岁及以上患者的附加维持治疗药物。本综述介绍了关于治疗重度哮喘的已批准生物制剂的最新证据，并讨论了未满足的需求和未来展望，重点关注儿童和青少年年龄组。
