Pavord Ian D, Wechsler Michael E, Busse William W, Domingo Christian, Xia Changming, Gall Rebecca, Pandit-Abid Nami, Jacob-Nara Juby A, Radwan Amr, Rowe Paul J, Deniz Yamo
National Institute for Health and Care Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colo.
J Allergy Clin Immunol Glob. 2025 Apr 15;4(3):100474. doi: 10.1016/j.jacig.2025.100474. eCollection 2025 Aug.
The QUEST (ClinicalTrials.gov identifier NCT02414854) and TRAVERSE (NCT02134028) studies demonstrated the efficacy of dupilumab, 200 or 300 mg, versus placebo every 2 weeks for 52 weeks (QUEST) and dupilumab, 300 mg, for an additional 96 weeks (TRAVERSE) in patients with uncontrolled, moderate-to-severe asthma.
This analysis assessed dupilumab efficacy in patients from QUEST who enrolled in TRAVERSE and were stratified by a reduction in fractional exhaled nitric oxide (Feno) level by week 2 of QUEST.
Patients with an Feno level of at least 25 ppb at parent study baseline (PSBL) were defined as those with or without a minimally important Feno level reduction/response (a ≥20% reduction in patients with an Feno level of ≥50 ppb and a reduction of >10 ppb in those with an Feno level of <50 ppb at PSBL) by week 2 of QUEST. We assessed annualized severe exacerbation rates (AERs) and changes from PSBL in prebronchodilator FEV value, 5-item Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score.
During QUEST, dupilumab (compared with placebo) reduced AER by 58% to 59% across Feno response subgroups (unadjusted AER = 0.392-0.523 for dupilumab vs 1.052-1.280 for placebo) and improved prebronchodilator FEV value regardless of Feno response. These improvements were sustained during TRAVERSE, with a slightly greater magnitude in Feno responders. Dupilumab also improved 5-item Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores independently of Feno responses.
Dupilumab sustained efficacy for up to 3 years in patients with and without a minimally important early reduction in Feno level. Greater improvements were seen in patients with an early reduction in Feno level, but patients without such a reduction also showed favorable outcomes during their treatment with dupilumab.
QUEST（ClinicalTrials.gov标识符NCT02414854）和TRAVERSE（NCT02134028）研究证明，对于未得到控制的中重度哮喘患者，每2周注射200或300毫克度普利尤单抗，持续52周（QUEST），以及额外注射300毫克度普利尤单抗96周（TRAVERSE）的疗效。
本分析评估了QUEST研究中入组TRAVERSE研究且根据QUEST第2周时呼出一氧化氮分数（Feno）水平降低情况进行分层的患者中，度普利尤单抗的疗效。
在母研究基线（PSBL）时Feno水平至少为25 ppb的患者，根据QUEST第2周时是否有最小重要Feno水平降低/反应（Feno水平≥50 ppb的患者降低≥20%，PSBL时Feno水平<50 ppb的患者降低>10 ppb）进行定义。我们评估了年化严重加重率（AER）以及支气管扩张剂前FEV值、5项哮喘控制问卷评分和哮喘生活质量问卷评分相对于PSBL的变化。
在QUEST期间，度普利尤单抗（与安慰剂相比）在Feno反应亚组中使AER降低了58%至59%（度普利尤单抗未调整AER = 0.392 - 0.523，安慰剂为1.052 - 1.280），并且无论Feno反应如何，均改善了支气管扩张剂前FEV值。这些改善在TRAVERSE期间得以维持，在Feno反应者中幅度稍大。度普利尤单抗还独立于Feno反应改善了5项哮喘控制问卷和哮喘生活质量问卷评分。
度普利尤单抗在有或没有早期最小重要Feno水平降低的患者中持续有效长达3年。Feno水平早期降低的患者改善更大，但没有这种降低的患者在接受度普利尤单抗治疗期间也显示出良好的结果。
