先控制，后耐受：生物制剂作为重度过敏性哮喘中过敏原免疫治疗的促成因素。

文献信息

中文摘要

尽管针对IgE、IL-5/IL-5Rα、IL-4Rα和胸腺基质淋巴细胞生成素（TSLP）的生物制剂在重度哮喘治疗方面取得了重大进展，但这些药物抑制2型炎症，却不能可靠地诱导持久的过敏原特异性耐受。过敏原免疫治疗（AIT）仍然是IgE介导的呼吸道过敏唯一可改变疾病的治疗选择，但历史上其在重度哮喘中的应用因未控制疾病中的安全性担忧而受到限制。我们提出“先控制，后耐受”框架，即生物制剂诱导的疾病控制创造一个窗口期，使皮下或舌下AIT能够安全启动。本叙述性综述综合了支持序贯生物制剂-AIT联合治疗的免疫学原理和临床证据，重点强调奥马珠单抗作为研究最充分的辅助治疗，以及度普利尤单抗和tezepelumab的新兴数据。我们讨论了生物标志物指导的患者选择、治疗顺序、合并过敏性鼻炎和慢性鼻窦炎、减少皮质类固醇使用的效应、感染风险、气道抗病毒免疫，以及围绕长期缓解的未解决问题。该框架的新颖之处在于重新界定生物制剂，不仅将其视为症状控制药物，而且将其视为解锁先前无法实现的疾病修饰干预的促进因素，可能将重度过敏性哮喘管理从控制转向持久免疫学缓解。我们得出结论：生物制剂启用的AIT是一种有前景但定义尚不充分的策略，并概述了将其确立为循证临床路径所需的前瞻性试验、标准化表型分析和安全性登记。

英文摘要

Despite major advances in the treatment of severe asthma with biologics targeting IgE, IL-5/IL-5Rα, IL-4Rα, and thymic stromal lymphopoietin (TSLP), these agents suppress type 2 inflammation without reliably inducing durable allergen-specific tolerance. Allergen immunotherapy (AIT) remains the only disease-modifying option for IgE-mediated respiratory allergy, yet its use in severe asthma has historically been restricted by safety concerns in uncontrolled disease. We propose a "control first, tolerance second" framework, whereby biologic-induced disease control creates a window enabling safe initiation of subcutaneous or sublingual AIT. This narrative review synthesizes the immunological rationale and clinical evidence supporting sequential biologic-AIT combination, with emphasis on omalizumab as the best-studied adjunct and emerging data on dupilumab and tezepelumab. We address biomarker-guided patient selection, treatment sequencing, comorbid allergic rhinitis and chronic rhinosinusitis, corticosteroid-sparing effects, infection risk, airway antiviral immunity, and unresolved questions around long-term remission. The novelty of this framework lies in reframing biologics not merely as symptom-control agents but as facilitators that unlock a previously inaccessible disease-modifying intervention, potentially shifting severe allergic asthma management from control toward durable immunological remission. We conclude that biologic-enabled AIT is a promising but insufficiently defined strategy, and outline the prospective trials, standardized phenotyping, and safety registries needed to establish it as an evidence-based clinical pathway.