抗IL5/Rα治疗失败后二线度普利尤单抗：重度哮喘的缓解率与临床结局
Second-line dupilumab after anti-IL5/Rα failure: remission rates and clinical outcomes in severe asthma.
文献信息
| PMID | 42874915 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Susanne Hansen |
| 作者单位 | Department of Respiratory Medicine and Infectious Diseases - Copenhagen University Hospital - Bispebjerg, Copenhagen, Denmark. Electronic address: Susanne.Hansen.10@regionh.dk. |
| 期刊 | The journal of allergy and clinical immunology. In practice |
| SCI 分区 | Q1 |
| IF | 7.7 |
| 研究类型 | 临床研究 · 临床 |
| 所属专科 | 鼻科 |
中文摘要
背景： 重度哮喘患者中10-25%会更换生物制剂治疗，但一线生物制剂失败后的缓解率仍缺乏充分描述。
目的： 评估抗IL5/Rα治疗失败后转换为抗IL4/13治疗后的临床缓解情况。
方法： 这项观察性队列研究纳入了所有丹麦成人重度哮喘患者，这些患者在接受抗IL5/Rα治疗未能达到缓解后转换为二线抗IL4/13治疗。12个月时的缓解通过四个维度评估：无急性加重、未使用维持性口服糖皮质激素（mOCS）、ACQ-6 ≤1.5、FEV1 >80%预计值（FEV1%pred）。
结果： 共纳入173例患者（中位年龄55岁；45%为女性），其中79%因缺乏治疗效果而转换治疗。达到各缓解维度的患者比例从生物制剂前基线到转换时及随访时逐步增加。12个月时，分别有66%、75%、54%和39%的患者达到急性加重、mOCS、ACQ-6和FEV1%pred标准；17%达到全部四个维度缓解。肺功能受损是未缓解者中最持续未满足的标准。生物制剂前和转换前生物标志物不能预测缓解，而特应性皮炎（33% vs. 16%，p=0.05）和鼻息肉（75% vs. 49%，p=0.02）与缓解相关，COPD与未缓解相关（4% vs. 34%，p=0.003）。
结论： 在一线抗IL5/Rα治疗未达到缓解的重度哮喘患者中，近五分之一在转换为抗IL4/13治疗后达到缓解，提示跨类别转换对反应不佳的患者是一种有效策略。肺功能受损和缺乏广泛T2共病预示缓解可能性较低。
英文摘要
BACKGROUND: Switching biologic therapies occurs in 10-25% of severe asthma patients, yet remission rates after first-line biologic failure remain poorly characterised.
OBJECTIVE: To assess clinical remission after switching from anti-IL5/Rα to anti-IL4/13 therapy following treatment failure.
METHODS: This observational cohort study included all Danish adults with severe asthma switching to second-line anti-IL4/13 after failing to achieve remission on anti-IL5/Rα. Remission at 12 months was assessed by four domains: no exacerbations, no maintenance oral corticosteroid use (mOCS), ACQ-6 ≤1.5, and FEV1 >80% predicted (FEV1%pred).
RESULTS: A total of 173 patients were included (median age 55; 45% female), with 79% switching due to lack of treatment effect. The proportion of patients meeting each remission domain increased progressively from pre-biologic baseline to switching and follow-up. At 12 months, 66%, 75%, 54%, and 39% met the exacerbation, mOCS, ACQ-6, and FEV1%pred criteria, respectively; 17% achieved full four-domain remission. Impaired lung function was the most persistent unmet criterion among non-remitters. Pre-biologic and pre-switch biomarkers did not predict remission, whereas atopic dermatitis (33% vs. 16%, p=0.05) and nasal polyps (75% vs. 49%, p=0.02) were associated with remission, and COPD with non-remission (4% vs. 34%, p=0.003).
CONCLUSION: In severe asthma patients not achieving remission on first-line anti-IL5/Rα, nearly one in five achieved remission after switching to anti-IL4/13, suggesting that interclass switching is an effective strategy for patients with inadequate response. Impaired lung function and absence of broad T2 comorbidity predict a lower likelihood of remission.