早期一过性血嗜酸性粒细胞升高不影响度普利尤单抗治疗中重度哮喘的长期疗效
2026/03/05
摘要
背景：度普利尤单抗临床试验中观察到血嗜酸性粒细胞计数（BEC）一过性升高，但这种升高极少伴随临床症状。
目的：本研究旨在评估血嗜酸性粒细胞计数早期升高对长期治疗结局的影响。
方法：本研究纳入 Ⅲ 期 QUEST 研究（NCT02414854，52 周）中年龄≥12 岁、中重度 2 型哮喘患者，这些患者后续进入开放标签拓展研究 TRAVERSE（NCT02134028，96 周）。根据血嗜酸性粒细胞计数进行分层，即QUEST 研究第 12 周内是否出现≥2 倍的血嗜酸性粒细胞计数升高，或 QUEST 研究期间是否出现血嗜酸性粒细胞计数升高（定义为基线＜500 个 /μL，但研究中任意时间≥500 个 /μL）。主要终点包括：重度急性加重年化率、支气管舒张前 1 秒用力呼气容积（FEV1）较母研究基线的变化、5 项哮喘控制问卷评分，以及 2 型炎症生物标志物水平。
结果：截至第 12 周，度普利尤单抗组36.6%的患者出现≥2 倍血嗜酸性粒细胞计数升高，安慰剂组为21.7%。整个 QUEST 研究期间，度普利尤单抗组31.3%出现血嗜酸性粒细胞计数升高，安慰剂组为28.0%。在 QUEST 第 52 周，各亚组中，度普利尤单抗较安慰剂均降低了重度急性加重年化率，改善支气管舒张前 FEV1 和问卷评分，并降低生物标志物水平。所有亚组的疗效在 TRAVERSE 研究第 96 周均得以维持。
结论：对于未控制的中重度 2 型哮喘患者，无论是否出现早期一过性血嗜酸性粒细胞计数升高，度普利尤单抗治疗长达 148 周均可减少哮喘急性加重、改善肺功能和哮喘控制。总体安全性与度普利尤单抗已知的安全性特征一致。
Transient early blood eosinophil increases do not affect dupilumab's long-term efficacy in patients with moderate-to-severe asthma.
Pavord ID, Lugogo NL, Castro M, Papi A, Bourdin A, Wechsler ME, Côté A, Chapman KR, Xia C, Soliman M, Pandit-Abid N, Jacob-Nara JA, Sacks H.
Abstract
BACKGROUND:
Transient increases in blood eosinophil count (BEC) have been observed in dupilumab clinical trials but are rarely associated with clinical symptoms.
OBJECTIVE:
We assessed the effect of early increases in BEC on long-term treatment outcomes.
METHODS:
Patients aged ≥12 years with moderate-to-severe type 2 asthma from the phase 3 QUEST study (NCT02414854; 52 weeks) who enrolled onto the TRAVERSE open-label extension study (NCT02134028; 96 weeks) were stratified by BEC: with or without ≥2-fold BEC increase any time by week 12 of QUEST, or presence or absence of increased BEC any time during QUEST (defined as <500 cells/μL at baseline but ≥500 cells/μL at any time during QUEST). End points included annualized severe exacerbation rate and change from parent study baseline in prebronchodilator forced expiratory volume in 1 second (FEV1), 5-item Asthma Control Questionnaire, and type 2 inflammatory biomarkers.
RESULTS:
A total of 36.6% of dupilumab-treated patients versus 21.7% of placebo-receiving patients experienced a ≥2-fold BEC change by week 12, while 31.3% versus 28.0% experienced increased BEC any time during QUEST. Dupilumab versus placebo reduced annualized severe exacerbation rate, improved prebronchodilator FEV1 and questionnaire scores, and reduced biomarkers across subgroups at week 52 of QUEST. Improvements were maintained in all subgroups through week 96 of TRAVERSE.
CONCLUSIONS:
Dupilumab reduced asthma exacerbations and improved lung function and asthma control up to 148 weeks in patients with uncontrolled moderate-to-severe type 2 asthma irrespective of early transient increases in BEC. Overall safety was consistent with the known dupilumab safety profile.
背景：度普利尤单抗临床试验中观察到血嗜酸性粒细胞计数（BEC）一过性升高，但这种升高极少伴随临床症状。
目的：本研究旨在评估血嗜酸性粒细胞计数早期升高对长期治疗结局的影响。
方法：本研究纳入 Ⅲ 期 QUEST 研究（NCT02414854，52 周）中年龄≥12 岁、中重度 2 型哮喘患者，这些患者后续进入开放标签拓展研究 TRAVERSE（NCT02134028，96 周）。根据血嗜酸性粒细胞计数进行分层，即QUEST 研究第 12 周内是否出现≥2 倍的血嗜酸性粒细胞计数升高，或 QUEST 研究期间是否出现血嗜酸性粒细胞计数升高（定义为基线＜500 个 /μL，但研究中任意时间≥500 个 /μL）。主要终点包括：重度急性加重年化率、支气管舒张前 1 秒用力呼气容积（FEV1）较母研究基线的变化、5 项哮喘控制问卷评分，以及 2 型炎症生物标志物水平。
结果：截至第 12 周，度普利尤单抗组36.6%的患者出现≥2 倍血嗜酸性粒细胞计数升高，安慰剂组为21.7%。整个 QUEST 研究期间，度普利尤单抗组31.3%出现血嗜酸性粒细胞计数升高，安慰剂组为28.0%。在 QUEST 第 52 周，各亚组中，度普利尤单抗较安慰剂均降低了重度急性加重年化率，改善支气管舒张前 FEV1 和问卷评分，并降低生物标志物水平。所有亚组的疗效在 TRAVERSE 研究第 96 周均得以维持。
结论：对于未控制的中重度 2 型哮喘患者，无论是否出现早期一过性血嗜酸性粒细胞计数升高，度普利尤单抗治疗长达 148 周均可减少哮喘急性加重、改善肺功能和哮喘控制。总体安全性与度普利尤单抗已知的安全性特征一致。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（J Allergy Clin Immunol. 2026 Feb;157(2):363-373. doi: 10.1016/j.jaci.2025.07.037. Epub 2025 Nov 14. PMID: 41242639.）
（J Allergy Clin Immunol. 2026 Feb;157(2):363-373. doi: 10.1016/j.jaci.2025.07.037. Epub 2025 Nov 14. PMID: 41242639.）
Transient early blood eosinophil increases do not affect dupilumab's long-term efficacy in patients with moderate-to-severe asthma.
Pavord ID, Lugogo NL, Castro M, Papi A, Bourdin A, Wechsler ME, Côté A, Chapman KR, Xia C, Soliman M, Pandit-Abid N, Jacob-Nara JA, Sacks H.
Abstract
BACKGROUND:
Transient increases in blood eosinophil count (BEC) have been observed in dupilumab clinical trials but are rarely associated with clinical symptoms.
OBJECTIVE:
We assessed the effect of early increases in BEC on long-term treatment outcomes.
METHODS:
Patients aged ≥12 years with moderate-to-severe type 2 asthma from the phase 3 QUEST study (NCT02414854; 52 weeks) who enrolled onto the TRAVERSE open-label extension study (NCT02134028; 96 weeks) were stratified by BEC: with or without ≥2-fold BEC increase any time by week 12 of QUEST, or presence or absence of increased BEC any time during QUEST (defined as <500 cells/μL at baseline but ≥500 cells/μL at any time during QUEST). End points included annualized severe exacerbation rate and change from parent study baseline in prebronchodilator forced expiratory volume in 1 second (FEV1), 5-item Asthma Control Questionnaire, and type 2 inflammatory biomarkers.
RESULTS:
A total of 36.6% of dupilumab-treated patients versus 21.7% of placebo-receiving patients experienced a ≥2-fold BEC change by week 12, while 31.3% versus 28.0% experienced increased BEC any time during QUEST. Dupilumab versus placebo reduced annualized severe exacerbation rate, improved prebronchodilator FEV1 and questionnaire scores, and reduced biomarkers across subgroups at week 52 of QUEST. Improvements were maintained in all subgroups through week 96 of TRAVERSE.
CONCLUSIONS:
Dupilumab reduced asthma exacerbations and improved lung function and asthma control up to 148 weeks in patients with uncontrolled moderate-to-severe type 2 asthma irrespective of early transient increases in BEC. Overall safety was consistent with the known dupilumab safety profile.
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