儿童过敏性疾病生物制剂和小分子治疗的最新进展。

文献信息

中文摘要

生物制剂已经彻底改变了儿童严重过敏性疾病中传统治疗无法控制的治疗格局。这些疾病通常由免疫反应失调驱动，往往由2型通路介导。通过靶向这些通路，生物制剂具有治疗一种或多种过敏性疾病的潜力。因此，现在优先采用“达标治疗”策略，允许以个性化方法治疗过敏性疾病。先驱性抗IgE单克隆抗体奥马珠单抗最初被批准用于治疗中重度过敏性哮喘，现在被批准用于慢性自发性荨麻疹（CSU）、伴鼻息肉的慢性鼻窦炎（CRSwNP）和食物过敏（FA），突显了生物制剂靶向多种过敏性疾病的能力。其他生物制剂已在哮喘和其他过敏性疾病中开发，包括美泊利单抗（抗IL5）、贝那利珠单抗（抗IL5受体）、度普利尤单抗（抗IL-4受体α），以及最近的替泽利尤单抗（抗TSLP）。在儿童和/或青少年中的临床试验已证明它们在哮喘、特应性皮炎（AD）、CSU以及最近在嗜酸性食管炎（EoE）和FA中的疗效和安全性，并得到真实世界研究的证实。除生物制剂外，小分子如Janus激酶抑制剂靶向其他关键通路，并已在AD中获得批准，其他过敏性疾病中的临床试验正在进行中。在儿科特定背景下，这些治疗提出了问题，特别是关于生物制剂的选择和目标。长期来看，持续疗效、安全性以及对过敏性疾病自然史的影响需要进一步研究。本综述的目的是讨论生物制剂和小分子在儿童过敏性疾病中应用的最新数据，并强调知识中剩余的空白。

英文摘要

Biologics have revolutionized the treatment of severe allergic diseases in children that cannot be controlled by conventional treatments. These diseases are commonly driven by dysregulation of immune response, often driven by Type 2 pathways. By targeting them, biologics have the potential for treating one or more allergic diseases. Thus, a "treat to target" strategy is now prioritized, allowing treatment of allergic diseases in a personalized approach. The pioneer anti-IgE monoclonal antibody, omalizumab, was initially indicated for the treatment of moderate to severe allergic asthma and is now indicated for chronic spontaneous urticaria (CSU), chronic rhinosinusitis with nasal polyps (CRSwNP), and food allergy (FA), highlighting the ability of biologics to target multiple allergic diseases. Other biologics have been developed in asthma and other allergic diseases, including mepolizumab (anti-IL5), benralizumab (anti-IL5 receptor), dupilumab (anti-IL-4 receptor α), and more recently tezepelumab (anti-TSLP). Clinical trials in children and/or teenagers have demonstrated their efficacy and safety, confirmed by real-life studies, in asthma, atopic dermatitis (AD), CSU, and more recently in eosinophilic esophagitis (EoE) and FA. Beyond biologics, small molecules such as Janus kinase inhibitors target other key pathways and have already been approved in AD, with ongoing clinical trials in other allergic diseases. In the pediatric specific context, these treatments raise questions, particularly regarding the choice of biologics and the goals. In the long term, the sustained efficacy, safety and impact on the natural history of allergic diseases need to be further studied. The aim of this review is to discuss the most recent data in the use of biologics and small molecules in pediatric allergic diseases and to highlight the remaining gaps in knowledge.