National Heart and Lung Institute, Imperial College London, London, UK.
Pediatric Respiratory Medicine, Royal Brompton and Harefield Hospitals, London, UK.
Pediatr Pulmonol. 2024 Dec;59(12):3057-3074. doi: 10.1002/ppul.27218. Epub 2024 Sep 13.
Novel biologics (targeted antibody therapies) have revolutionized the management of severe childhood asthma. However, it is important that the right biologic is selected for the right patient, and understanding the evidence base for each biologic is crucial. Currently, four biologics (all monoclonal antibodies) are licensed in the UK for the treatment of children with severe asthma - omalizumab (Xolair), mepolizumab (Nucala), and dupilumab (Dupixent) in children aged 6 years and over; and tezepelumab (Tezspire), only in children aged 12 years and over. Tezepelumab is the only licensed biological that may be beneficial in severe asthma without evidence of Type 2 inflammation. All have a good safety profile but varying degrees of clinical efficacy in children, with wide variation in treatment responsiveness between individual patients. When selecting biologics for severe asthma, it is essential to remember the limitations of the current pediatric evidence. At present, there are no results from randomized, head-to-head trials of biologics in severe asthma. TREAT is an ongoing trial comparing omalizumab to mepolizumab and will be one of the first to provide such evidence. We must be especially aware of the dangers of extrapolating data from adults to children, because the pathophysiology and role of biomarkers may differ significantly from adult asthma. Given the current level of knowledge, even after treatment has been initiated, children should be regularly reviewed to determine the efficacy of treatment, side-effect profile and consideration of when treatment with the biologic should be discontinued.
新型生物制剂（靶向抗体疗法）彻底改变了儿童重度哮喘的治疗模式。然而，为患者选择合适的生物制剂非常重要，了解每种生物制剂的证据基础至关重要。目前，有四种生物制剂（均为单克隆抗体）在英国获得许可，用于治疗儿童重度哮喘——奥马珠单抗（茁乐）、美泊利珠单抗（美普力）和度普利尤单抗（度必特）适用于 6 岁及以上儿童；替泽泊单抗（特泽泊单抗）仅适用于 12 岁及以上儿童。替泽泊单抗是唯一一种有证据表明对无 2 型炎症的重度哮喘可能有益的生物制剂。所有这些生物制剂在儿童中的安全性良好，但疗效存在差异，且个体患者之间的治疗反应差异很大。在为重度哮喘选择生物制剂时，务必记住当前儿科证据的局限性。目前，尚无重度哮喘中生物制剂的随机、头对头试验结果。TREAT 是一项正在进行的比较奥马珠单抗与美泊利珠单抗的试验，将是首批提供此类证据的试验之一。我们必须特别注意将成人数据外推至儿童的危险，因为儿童的病理生理学和生物标志物的作用可能与成人哮喘有很大不同。鉴于目前的知识水平，即使在开始治疗后，也应定期对儿童进行评估，以确定治疗的疗效、副作用情况，并考虑何时应停止使用生物制剂。
