度普利尤单抗与IL-5抑制剂在哮喘中的眼部安全性比较

文献信息

中文摘要

背景： 眼部不良事件（OAEs）是接受生物制剂治疗的哮喘患者临床关注的问题。尽管度普利尤单抗在特应性皮炎（AD）中与OAEs相关，但其在哮喘中相较于白细胞介素-5（IL-5）抑制剂的眼部安全性仍不明确。
目的： 采用目标试验模拟框架，比较成人哮喘患者中度普利尤单抗与IL-5抑制剂发生OAEs的风险。
方法： 这项回顾性队列研究利用TriNetX美国协作网络（2018-2025）识别开始使用度普利尤单抗或IL-5抑制剂（美泊利单抗或贝那利珠单抗）的成人哮喘患者，排除治疗开始前12个月内发生OAEs者。经1:1倾向评分匹配后，评估OAEs复合结局。使用Cox比例风险回归估计6个月随访期间的校正风险比（aHRs）。
结果： 匹配后识别出7,073对，其中少数患有AD（0.9%），但相当一部分合并慢性阻塞性肺疾病（COPD）（约30%）。与既往在AD人群中的研究不同，两组总体OAE发生率均较低，但度普利尤单抗风险高于IL-5抑制剂（2.6% vs 2.1%；aHR，1.25；95% CI，1.01-1.55）。结膜炎风险也更高（1.5% vs 1.1%；aHR，1.38；95% CI，1.03-1.86），而干眼综合征无显著差异（aHR，1.15；95% CI，0.80-1.66）。亚组分析未显示年龄、性别、过敏性鼻炎或COPD状态存在效应修饰的证据（交互作用P均>.05），尽管年轻成人中OAEs风险更高，年轻成人和男性成人中结膜炎风险更高。结果总体一致，但在排除AD、高嗜酸性粒细胞综合征或干燥综合征患者后（aHR，1.23；95% CI，0.98-1.54）或在持续使用生物制剂者中（aHR，1.29；95% CI，0.87-1.93），显著性未保留。
结论： 在哮喘患者6个月随访中，度普利尤单抗相较于IL-5抑制剂与轻度更高但总体不常见的OAEs风险相关（2.6% vs 2.1%），该发生率显著低于既往在AD人群中报告的8-28%。这一风险主要由结膜炎驱动，在年轻成人、男性以及合并AD的患者中最为明显，提示AD也可能促成该不良效应。尤其在这些亚组中，持续眼部监测是必要的。

英文摘要

BACKGROUND: Ocular adverse events (OAEs) are a clinical concern among patients with asthma receiving biologic therapy. Although dupilumab is associated with OAEs in atopic dermatitis (AD), its comparative ocular safety versus interleukin-5 (IL-5) inhibitors in asthma remains unclear.
OBJECTIVE: To compare the risk of OAEs between dupilumab and IL-5 inhibitors in adults with asthma using a target trial emulation framework.
METHODS: This retrospective cohort study utilized the TriNetX US Collaborative Network (2018-2025) to identify adults with asthma initiating dupilumab or IL-5 inhibitors (mepolizumab or benralizumab), excluding those with OAEs within the 12 months before treatment initiation. After 1:1 propensity score matching, the composite outcome of OAEs was assessed. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards regression over a 6-month follow-up.
RESULTS: After matching, 7,073 pairs were identified, with few having AD (0.9%) but substantial chronic obstructive pulmonary disease (COPD) comorbidity (∼30%). Unlike prior studies in AD populations, overall OAE incidence was low in both groups, though risk was higher with dupilumab than IL-5 inhibitors (2.6% vs 2.1%; aHR, 1.25; 95% CI, 1.01-1.55). Conjunctivitis risk was also higher (1.5% vs 1.1%; aHR, 1.38; 95% CI, 1.03-1.86), whereas no significant difference was observed for dry eye syndrome (aHR, 1.15; 95% CI, 0.80-1.66). Subgroup analyses showed no evidence of effect modification by age, sex, allergic rhinitis, or COPD status (all P for interaction >.05), although risk was higher among younger adults for OAEs and among younger and male adults for conjunctivitis. Findings were generally consistent, though significance was not retained after excluding patients with AD, hypereosinophilic syndrome or Sjögren's syndrome (aHR, 1.23; 95% CI, 0.98-1.54) or among persistent biologic use (aHR, 1.29; 95% CI, 0.87-1.93).
CONCLUSION: Dupilumab was associated with a modestly higher, but overall infrequent, risk of OAEs than IL-5 inhibitors in asthma over 6 months (2.6% vs 2.1%), a rate substantially lower than the 8-28% previously reported in AD populations. This risk, driven primarily by conjunctivitis, was most pronounced among younger adults, men, and patients with comorbid AD, suggesting that AD may also contribute to this adverse effect. Continued ocular monitoring is warranted, particularly in these subgroups.