生物制剂治疗儿童慢性鼻窦炎伴鼻息肉：疗效与安全性的系统评价

文献信息

中文摘要

慢性鼻窦炎伴鼻息肉（CRSwNP）在儿童人群中不常见，但可能显著损害生活质量。成人数据支持靶向2型炎症通路的生物制剂，而儿童证据仍然稀少且多为间接证据。本系统评价旨在总结关于疗效和安全性的现有证据，而非估计精确的治疗效应。按照PRISMA 2020指南进行了系统评价。检索了PubMed、Scopus和Cochrane Library数据库，从建库至2026年3月，纳入研究生物制剂用于儿童CRSwNP或儿童2型气道疾病并报告CRSwNP相关鼻窦结局的研究。聚焦于囊性纤维化相关鼻息肉病或变应性真菌性鼻窦炎（AFRS）的研究被排除在主要合成之外，仅保留用于敏感性/背景分析。使用与设计相适应的工具评估偏倚风险。在404条识别记录中，六项研究符合定性评价条件。排除囊性纤维化相关鼻息肉病和AFRS后，四项研究（三项病例系列和一项回顾性观察性研究）被保留在主要合成中；两项研究被考虑用于敏感性分析。现有证据主要为低级别、异质性大，且基于小样本。Dupilumab、omalizumab和mepolizumab在选定的2型炎症表型中显示出潜在获益信号，但鼻窦结局报告不一致。未报告重大治疗相关安全性问题，尽管不良事件报告不一致，且随访时间有限且多变。对于dupilumab，儿童CRSwNP特异性安全性数据仍然稀少，更广泛处方信息中描述的已知不良事件，包括注射部位反应、嗜酸性粒细胞增多、结膜炎、皮肤反应和关节痛，需要主动监测。生物制剂可能代表对选定的难治性2型炎症CRSwNP儿童患者一种有前景的减少类固醇用量的选择。然而，当前证据主要基于病例系列和间接队列；因此，结论应谨慎并视为产生假设。需要具有标准化鼻窦结局和更长随访时间的前瞻性儿童研究。

英文摘要

Chronic rhinosinusitis with nasal polyps (CRSwNP) is uncommon in pediatric populations but may significantly impair quality of life. Adult data support biologics targeting type 2 inflammatory pathways, whereas pediatric evidence remains sparse and largely indirect. This systematic review aimed to summarize the available evidence on both efficacy and safety, rather than to estimate a precise treatment effect. A systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Scopus, and Cochrane Library databases were searched from inception to March 2026 for studies investigating biologics in pediatric CRSwNP or pediatric type 2 airway disease with CRSwNP-related sinonasal outcomes. Studies focused on cystic fibrosis-associated nasal polyposis or allergic fungal rhinosinusitis (AFRS) were excluded from the primary synthesis and retained only for sensitivity/contextual analyses. Risk of bias was assessed using design-appropriate tools. Of 404 identified records, six studies were eligible for qualitative review. Four studies (three case series and one retrospective observational study) were retained in the primary synthesis after exclusion of cystic fibrosis-associated nasal polyposis and AFRS; two studies were considered in sensitivity analyses. The available evidence was predominantly low-level, heterogeneous, and based on small samples. Dupilumab, omalizumab, and mepolizumab showed signals of potential benefit in selected type 2 inflammatory phenotypes, but sinonasal outcomes were inconsistently reported. No major treatment-related safety issues were reported, although adverse-event reporting was inconsistent, and follow-up duration was limited and variable. For dupilumab, pediatric CRSwNP-specific safety data remain sparse, and known adverse events described in broader prescribing information, including injection-site reactions, eosinophilia, conjunctivitis, skin reactions, and arthralgia, require active monitoring. Biologics may represent a promising steroid-sparing option for selected pediatric patients with refractory type 2 inflammatory CRSwNP. However, current evidence is predominantly based on case series and indirect cohorts; therefore, conclusions should be considered cautious and hypothesis-generating. Prospective pediatric studies with standardized sinonasal outcomes and longer follow-up are required.