血嗜酸性粒细胞早期短暂增多不影响度普利尤单抗对中重度哮喘患者的长期疗效
2025/11/28
摘要
背景：在度普利尤单抗临床试验中观察到血液嗜酸性粒细胞计数（BEC）出现短暂升高，但很少伴有临床症状。
目的：评估BEC早期升高对长期治疗结局的影响。
方法：来自3期QUEST研究（NCT02414854；为期52周）且年龄≥12岁的中重度2型哮喘患者，若其参加了TRAVERSE开放标签扩展研究（NCT02134028；为期96周），则根据BEC进行分层：在QUEST研究第12周前任何时间BEC升高≥2倍或未升高，或在QUEST研究期间任何时间BEC升高或未升高（定义为基线时＜500个细胞/μL，但在QUEST研究期间任何时间点≥500个细胞/μL）。终点指标包括年化急性加重率（AER）、与母研究基线（PSBL）相比支气管扩张剂使用前第1秒用力呼气容积（FEV1）的变化、5项哮喘控制问卷（ACQ - 5）评分以及2型炎症生物标志物。
结果：在QUEST研究第12周时，接受度普利尤单抗治疗的患者中有36.6%的人BEC变化≥2倍，而接受安慰剂治疗的患者中这一比例为21.7%；在QUEST研究期间任何时间，分别有31.3%和28.0%的患者BEC升高。在QUEST研究第52周时，与安慰剂组相比，度普利尤单抗降低了AER，改善了支气管扩张剂使用前FEV1和ACQ - 5评分，并降低了各亚组的生物标志物水平。在TRAVERSE研究第96周时，所有亚组的改善情况均得以维持。
结论：对于未得到控制的中重度2型哮喘患者，无论BEC早期是否短暂升高，度普利尤单抗在长达148周的时间里均可减少哮喘急性加重，改善肺功能和哮喘控制情况。总体安全性与已知的度普利尤单抗安全性特征一致。
Transient Early Blood Eosinophil Increases Do Not Affect Dupilumab's Long-Term Efficacy in Patients with Moderate-to-Severe Asthma
Ian D Pavord, Njira L Lugogo, Mario Castro, Alberto Papi, Arnaud Bourdin, Michael E Wechsler, Andréanne Côté, Kenneth R Chapman, Changming Xia, Mena Soliman, Nami Pandit-Abid, Juby A Jacob-Nara, Harry Sacks
Abstract
Background: Transient increases in blood eosinophil count (BEC) have been observed in dupilumab clinical trials but are rarely associated with clinical symptoms.
Objective: To assess 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 in the TRAVERSE open-label extension study (NCT02134028; 96 weeks) were stratified by BEC: with/without ≥2-fold BEC increase any time by week 12 of QUEST or presence/absence of increased BEC any time during QUEST (defined as <500 cells/μL at baseline but ≥500 cells/μL at any time point during QUEST). Endpoints included annualized exacerbation rate (AER) and change from parent study baseline (PSBL) in pre-bronchodilator forced expiratory volume in 1 second (FEV1), 5-item Asthma Control Questionnaire (ACQ-5), and type 2 inflammatory biomarkers.
Results: 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 AER, improved pre-bronchodilator FEV1 and ACQ-5 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：在度普利尤单抗临床试验中观察到血液嗜酸性粒细胞计数（BEC）出现短暂升高，但很少伴有临床症状。
目的：评估BEC早期升高对长期治疗结局的影响。
方法：来自3期QUEST研究（NCT02414854；为期52周）且年龄≥12岁的中重度2型哮喘患者，若其参加了TRAVERSE开放标签扩展研究（NCT02134028；为期96周），则根据BEC进行分层：在QUEST研究第12周前任何时间BEC升高≥2倍或未升高，或在QUEST研究期间任何时间BEC升高或未升高（定义为基线时＜500个细胞/μL，但在QUEST研究期间任何时间点≥500个细胞/μL）。终点指标包括年化急性加重率（AER）、与母研究基线（PSBL）相比支气管扩张剂使用前第1秒用力呼气容积（FEV1）的变化、5项哮喘控制问卷（ACQ - 5）评分以及2型炎症生物标志物。
结果：在QUEST研究第12周时，接受度普利尤单抗治疗的患者中有36.6%的人BEC变化≥2倍，而接受安慰剂治疗的患者中这一比例为21.7%；在QUEST研究期间任何时间，分别有31.3%和28.0%的患者BEC升高。在QUEST研究第52周时，与安慰剂组相比，度普利尤单抗降低了AER，改善了支气管扩张剂使用前FEV1和ACQ - 5评分，并降低了各亚组的生物标志物水平。在TRAVERSE研究第96周时，所有亚组的改善情况均得以维持。
结论：对于未得到控制的中重度2型哮喘患者，无论BEC早期是否短暂升高，度普利尤单抗在长达148周的时间里均可减少哮喘急性加重，改善肺功能和哮喘控制情况。总体安全性与已知的度普利尤单抗安全性特征一致。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（J Allergy Clin Immunol. 2025 Nov 14:S0091-6749(25)01127-3. doi:10.1016/j.jaci.2025.07.037.）
Transient Early Blood Eosinophil Increases Do Not Affect Dupilumab's Long-Term Efficacy in Patients with Moderate-to-Severe Asthma
Ian D Pavord, Njira L Lugogo, Mario Castro, Alberto Papi, Arnaud Bourdin, Michael E Wechsler, Andréanne Côté, Kenneth R Chapman, Changming Xia, Mena Soliman, Nami Pandit-Abid, Juby A Jacob-Nara, Harry Sacks
Abstract
Background: Transient increases in blood eosinophil count (BEC) have been observed in dupilumab clinical trials but are rarely associated with clinical symptoms.
Objective: To assess 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 in the TRAVERSE open-label extension study (NCT02134028; 96 weeks) were stratified by BEC: with/without ≥2-fold BEC increase any time by week 12 of QUEST or presence/absence of increased BEC any time during QUEST (defined as <500 cells/μL at baseline but ≥500 cells/μL at any time point during QUEST). Endpoints included annualized exacerbation rate (AER) and change from parent study baseline (PSBL) in pre-bronchodilator forced expiratory volume in 1 second (FEV1), 5-item Asthma Control Questionnaire (ACQ-5), and type 2 inflammatory biomarkers.
Results: 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 AER, improved pre-bronchodilator FEV1 and ACQ-5 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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