度普利尤单抗对中重度哮喘患者黏液负荷的影响：VESTIGE研究
2025/11/28
摘要
研究背景：慢性黏液高分泌是导致哮喘患者气道阻塞的因素之一。
研究目的：根据基线黏液栓评分评估度普利尤单抗的疗效。
研究方法：在VESTIGE研究（NCT04400318）中，患有中重度哮喘、基线血嗜酸性粒细胞计数≥300个/μL且呼出气一氧化氮（FeNO）≥25 ppb的成人患者，接受每2周一次度普利尤单抗300 mg（n=72）或安慰剂（n=37）治疗，持续24周。事后分析包括：黏液栓评分相对于基线的变化；达到FeNO <25 ppb的患者比例；以及按基线黏液栓评分（高/低分别定义为评分≥4分/0-3.5分，评分源自高分辨率计算机断层扫描）分层的预计值百分比用力呼气容积（FEV(1)）和用力肺活量（FVC）。
测量指标与主要结果：在第24周时，接受度普利尤单抗治疗的患者中具有高黏液栓评分的比例低于基线时（32.8% vs 67.2%）；而接受安慰剂治疗的患者中该比例保持相似（76.7% vs73.3%）。与安慰剂组相比，度普利尤单抗组患者在高/低黏液栓评分亚组中更有可能实现FeNO <25 ppb（优势比：6.64；P = 0.003 / 8.54；P = 0.024）。在高黏液栓评分亚组中，与安慰剂相比，度普利尤单抗显著提高了支气管扩张剂使用前/后的预计值百分比FEV(1）（最小二乘均值差 [95% CI]：16.77个百分点 [9.81-23.73]；P <0.0001 / 12.70 [3.87-21.52]；P = 0.0055）和支气管扩张剂使用前FVC（最小二乘均值差 [95% CI]：0.42 mL [0.17-0.66]；P = 0.001），并在数值上改善了支气管扩张剂使用后FVC（最小二乘均值差 [95% CI]：0.30 mL [0.01-0.59]；P = 0.0399）。
结论：对于基线黏液栓评分高的中重度哮喘患者，度普利尤单抗能降低黏液栓评分并改善肺功能；且无论基线黏液栓评分如何，度普利尤单抗均能增加实现FeNO <25 ppb的可能性。
Effect of Dupilumab on Mucus Burden in Patients with Moderate-to-Severe Asthma: The VESTIGE Trial.
Celeste, Porsbjerg; Eleanor M
Abstrast
RATIONALE: Chronic mucus hypersecretion contributes to airway obstruction in asthma.
OBJECTIVES: Assess dupilumab efficacy by baseline mucus plug score.
METHODS: In VESTIGE (NCT04400318), adults with moderate-to-severe asthma, baseline blood eosinophils ≥300 cells/μL, and fractional exhaled nitric oxide (FeNO) ≥25 ppb received dupilumab 300 mg (n=72) or placebo (n=37) every 2 weeks for 24 weeks. Post hoc analyses included mucus plug score change from baseline, and patient proportion achieving FeNO <25 ppb, percent predicted FEV(1), and FVC stratified by baseline mucus plug score (high/low defined by score ≥4/0-3.5, respectively, derived from high-resolution computed tomography scans).
MEASUREMENTS AND MAIN RESULTS: Fewer dupilumab-receiving patients had high mucus plug score at Week 24 than at baseline (32.8% vs 67.2%); proportions remained similar in placebo-receiving patients (76.7% vs. 73.3%). Dupilumab versus placebo recipients were more likely to achieve FeNO <25 ppb in high-/low-mucus-plug score subgroups (odds ratio: 6.64; P = 0.003/8.54; P = 0.024). Dupilumab versus placebo significantly increased pre-/post-bronchodilator percent predicted FEV(1) (least squares mean difference (LSMD) [95% CI]: 16.77 percentage points [9.81-23.73]; P <0.0001/12.70 [3.87-21.52]; P = 0.0055) and pre-bronchodilator FVC (LSMD [95% CI]: 0.42 mL [0.17-0.66]; P = 0.001), and numerically improved post-bronchodilator FVC (LSMD [95% CI]: 0.30 mL [0.01-0.59]; P = 0.0399) in the high-mucus-plug score subgroup.
CONCLUSIONS: Dupilumab reduced mucus plug scores and improved lung function in patients with moderate-to-severe asthma with high baseline mucus plug score, and increased the likelihood of achieving FeNO <25 ppb regardless of baseline mucus plug score.
研究背景：慢性黏液高分泌是导致哮喘患者气道阻塞的因素之一。
研究目的：根据基线黏液栓评分评估度普利尤单抗的疗效。
研究方法：在VESTIGE研究（NCT04400318）中，患有中重度哮喘、基线血嗜酸性粒细胞计数≥300个/μL且呼出气一氧化氮（FeNO）≥25 ppb的成人患者，接受每2周一次度普利尤单抗300 mg（n=72）或安慰剂（n=37）治疗，持续24周。事后分析包括：黏液栓评分相对于基线的变化；达到FeNO <25 ppb的患者比例；以及按基线黏液栓评分（高/低分别定义为评分≥4分/0-3.5分，评分源自高分辨率计算机断层扫描）分层的预计值百分比用力呼气容积（FEV(1)）和用力肺活量（FVC）。
测量指标与主要结果：在第24周时，接受度普利尤单抗治疗的患者中具有高黏液栓评分的比例低于基线时（32.8% vs 67.2%）；而接受安慰剂治疗的患者中该比例保持相似（76.7% vs73.3%）。与安慰剂组相比，度普利尤单抗组患者在高/低黏液栓评分亚组中更有可能实现FeNO <25 ppb（优势比：6.64；P = 0.003 / 8.54；P = 0.024）。在高黏液栓评分亚组中，与安慰剂相比，度普利尤单抗显著提高了支气管扩张剂使用前/后的预计值百分比FEV(1）（最小二乘均值差 [95% CI]：16.77个百分点 [9.81-23.73]；P <0.0001 / 12.70 [3.87-21.52]；P = 0.0055）和支气管扩张剂使用前FVC（最小二乘均值差 [95% CI]：0.42 mL [0.17-0.66]；P = 0.001），并在数值上改善了支气管扩张剂使用后FVC（最小二乘均值差 [95% CI]：0.30 mL [0.01-0.59]；P = 0.0399）。
结论：对于基线黏液栓评分高的中重度哮喘患者，度普利尤单抗能降低黏液栓评分并改善肺功能；且无论基线黏液栓评分如何，度普利尤单抗均能增加实现FeNO <25 ppb的可能性。
（中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校）
（Am J Respir Crit Care Med 2025 Oct 27;(0). DOI:10.1164/rccm.202410-1894OC.IF: 17.452）
Effect of Dupilumab on Mucus Burden in Patients with Moderate-to-Severe Asthma: The VESTIGE Trial.
Celeste, Porsbjerg; Eleanor M
Abstrast
RATIONALE: Chronic mucus hypersecretion contributes to airway obstruction in asthma.
OBJECTIVES: Assess dupilumab efficacy by baseline mucus plug score.
METHODS: In VESTIGE (NCT04400318), adults with moderate-to-severe asthma, baseline blood eosinophils ≥300 cells/μL, and fractional exhaled nitric oxide (FeNO) ≥25 ppb received dupilumab 300 mg (n=72) or placebo (n=37) every 2 weeks for 24 weeks. Post hoc analyses included mucus plug score change from baseline, and patient proportion achieving FeNO <25 ppb, percent predicted FEV(1), and FVC stratified by baseline mucus plug score (high/low defined by score ≥4/0-3.5, respectively, derived from high-resolution computed tomography scans).
MEASUREMENTS AND MAIN RESULTS: Fewer dupilumab-receiving patients had high mucus plug score at Week 24 than at baseline (32.8% vs 67.2%); proportions remained similar in placebo-receiving patients (76.7% vs. 73.3%). Dupilumab versus placebo recipients were more likely to achieve FeNO <25 ppb in high-/low-mucus-plug score subgroups (odds ratio: 6.64; P = 0.003/8.54; P = 0.024). Dupilumab versus placebo significantly increased pre-/post-bronchodilator percent predicted FEV(1) (least squares mean difference (LSMD) [95% CI]: 16.77 percentage points [9.81-23.73]; P <0.0001/12.70 [3.87-21.52]; P = 0.0055) and pre-bronchodilator FVC (LSMD [95% CI]: 0.42 mL [0.17-0.66]; P = 0.001), and numerically improved post-bronchodilator FVC (LSMD [95% CI]: 0.30 mL [0.01-0.59]; P = 0.0399) in the high-mucus-plug score subgroup.
CONCLUSIONS: Dupilumab reduced mucus plug scores and improved lung function in patients with moderate-to-severe asthma with high baseline mucus plug score, and increased the likelihood of achieving FeNO <25 ppb regardless of baseline mucus plug score.
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