依据治疗早期嗜酸性粒细胞状态分析度普利尤单抗治疗儿童哮喘的疗效：VOYAGE/EXCURSION研究事后分析
2026/07/31
摘要
背景：度普利尤单抗治疗期间可出现血嗜酸粒细胞一过性升高，但该现象极少伴随临床症状，其在儿童人群中的临床意义仍有待进一步评估。
目的：本研究旨在通过纳入完成VOYAGE研究并进入开放标签延伸研究EXCURSION的6～11岁2型哮喘患儿，评估治疗早期出现血嗜酸粒细胞升高患儿接受度普利尤单抗治疗的长期疗效与安全性。
方法：本事后分析评估早期嗜酸粒细胞升高亚组（基线血嗜酸粒细胞＜500个/μL，VOYAGE研究第12周≥500个/μL患儿）的年度重症哮喘急性发作率、支气管舒张剂使用前预计一秒用力呼气容积百分比（ppFEV1）及其Z评分较基线变化、访谈式5项哮喘控制问卷（ACQ-5IA）、呼出气一氧化氮（FeNO）、血嗜酸粒细胞、总免疫球蛋白E（总IgE）及安全性指标。
结果：VOYAGE 研究第12周，22.4%（35/156）患儿血嗜酸粒细胞≥500个/μL。VOYAGE 研究中，各亚组内度普利尤单抗相较安慰剂均可降低哮喘急性发作率，且该效应在EXCURSION研究中持续存在；由安慰剂转换至度普利尤单抗治疗的患儿，疗效与持续使用度普利尤单抗患儿相近。无论是否出现早期血嗜酸粒细胞升高，患儿ppFEV1、Z评分、ACQ-5IA评分、FeNO及总IgE水平均得到改善；各亚组间安全性无明显差异。
结论：随访长达2年，无论患儿是否出现治疗早期血嗜酸粒细胞升高，度普利尤单抗相较安慰剂均可减少哮喘急性发作、改善肺功能与哮喘控制水平、降低炎症标志物；出现早期嗜酸粒细胞升高患儿的度普利尤单抗安全性特征无改变。
Dupilumab outcomes in pediatric asthma by early eosinophil status: post hoc analysis of VOYAGE/EXCURSION.
Dell S, Guilbert TW, Deschildre A, Phipatanakul W, Papadopoulos NG, Murray CS, Xia C, Moraco A, Shams M, Bacharier LB.
Abstract
BACKGROUND:Transient increases in blood eosinophils may accompany dupilumab treatment, but these increases are rarely associated with clinical symptoms, and clinical significance in children needs further assessment.
OBJECTIVE:To evaluate the long-term efficacy and safety of dupilumab in children aged 6 to 11 years with type 2 asthma who completed the VOYAGE study and enrolled in the open-label extension study EXCURSION, and experienced an early increase in blood eosinophils.
METHODS:This post hoc analysis assessed annualized severe exacerbation rates, change from baseline in pre-bronchodilator percent predicted (pp) FEV1 and Z-score, 5-item Asthma Control Questionnaire Interviewer Administered (ACQ-5IA), fractional exhaled nitric oxide (FeNO), blood eosinophils and total IgE, and safety, in subgroups with early eosinophil increase (children with <500 cells/μL at baseline and ≥500 cells/μL at VOYAGE week 12).
RESULTS:At VOYAGE week 12, 22.4% (35/156) had ≥500 eosinophils/μL. Dupilumab reduced exacerbation rates versus placebo during VOYAGE across subgroups, with effects maintained in EXCURSION. Children switching from placebo to dupilumab also experienced consistent improvements similar to those who had been receiving dupilumab. Improvements in ppFEV1 and Z-score, ACQ-5IA, FeNO, and total IgE were observed in children with and without early blood eosinophil increases. No safety differences were observed across subgroups.
CONCLUSION: Dupilumab versus placebo reduced exacerbations, improved lung function and asthma control, and decreased inflammatory biomarkers in children with type 2 asthma across subgroups with and without early blood eosinophil increases up to 2 years. No differences in the dupilumab safety profile were observed in children with early eosinophil increases.
背景：度普利尤单抗治疗期间可出现血嗜酸粒细胞一过性升高，但该现象极少伴随临床症状，其在儿童人群中的临床意义仍有待进一步评估。
目的：本研究旨在通过纳入完成VOYAGE研究并进入开放标签延伸研究EXCURSION的6～11岁2型哮喘患儿，评估治疗早期出现血嗜酸粒细胞升高患儿接受度普利尤单抗治疗的长期疗效与安全性。
方法：本事后分析评估早期嗜酸粒细胞升高亚组（基线血嗜酸粒细胞＜500个/μL，VOYAGE研究第12周≥500个/μL患儿）的年度重症哮喘急性发作率、支气管舒张剂使用前预计一秒用力呼气容积百分比（ppFEV1）及其Z评分较基线变化、访谈式5项哮喘控制问卷（ACQ-5IA）、呼出气一氧化氮（FeNO）、血嗜酸粒细胞、总免疫球蛋白E（总IgE）及安全性指标。
结果：VOYAGE 研究第12周，22.4%（35/156）患儿血嗜酸粒细胞≥500个/μL。VOYAGE 研究中，各亚组内度普利尤单抗相较安慰剂均可降低哮喘急性发作率，且该效应在EXCURSION研究中持续存在；由安慰剂转换至度普利尤单抗治疗的患儿，疗效与持续使用度普利尤单抗患儿相近。无论是否出现早期血嗜酸粒细胞升高，患儿ppFEV1、Z评分、ACQ-5IA评分、FeNO及总IgE水平均得到改善；各亚组间安全性无明显差异。
结论：随访长达2年，无论患儿是否出现治疗早期血嗜酸粒细胞升高，度普利尤单抗相较安慰剂均可减少哮喘急性发作、改善肺功能与哮喘控制水平、降低炎症标志物；出现早期嗜酸粒细胞升高患儿的度普利尤单抗安全性特征无改变。
（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 Jun 30:S0091-6749(26)00446-X. doi: 10.1016/j.jaci.2026.06.012. Epub ahead of print. PMID: 42379525.）
（J Allergy Clin Immunol. 2026 Jun 30:S0091-6749(26)00446-X. doi: 10.1016/j.jaci.2026.06.012. Epub ahead of print. PMID: 42379525.）
Dupilumab outcomes in pediatric asthma by early eosinophil status: post hoc analysis of VOYAGE/EXCURSION.
Dell S, Guilbert TW, Deschildre A, Phipatanakul W, Papadopoulos NG, Murray CS, Xia C, Moraco A, Shams M, Bacharier LB.
Abstract
BACKGROUND:Transient increases in blood eosinophils may accompany dupilumab treatment, but these increases are rarely associated with clinical symptoms, and clinical significance in children needs further assessment.
OBJECTIVE:To evaluate the long-term efficacy and safety of dupilumab in children aged 6 to 11 years with type 2 asthma who completed the VOYAGE study and enrolled in the open-label extension study EXCURSION, and experienced an early increase in blood eosinophils.
METHODS:This post hoc analysis assessed annualized severe exacerbation rates, change from baseline in pre-bronchodilator percent predicted (pp) FEV1 and Z-score, 5-item Asthma Control Questionnaire Interviewer Administered (ACQ-5IA), fractional exhaled nitric oxide (FeNO), blood eosinophils and total IgE, and safety, in subgroups with early eosinophil increase (children with <500 cells/μL at baseline and ≥500 cells/μL at VOYAGE week 12).
RESULTS:At VOYAGE week 12, 22.4% (35/156) had ≥500 eosinophils/μL. Dupilumab reduced exacerbation rates versus placebo during VOYAGE across subgroups, with effects maintained in EXCURSION. Children switching from placebo to dupilumab also experienced consistent improvements similar to those who had been receiving dupilumab. Improvements in ppFEV1 and Z-score, ACQ-5IA, FeNO, and total IgE were observed in children with and without early blood eosinophil increases. No safety differences were observed across subgroups.
CONCLUSION: Dupilumab versus placebo reduced exacerbations, improved lung function and asthma control, and decreased inflammatory biomarkers in children with type 2 asthma across subgroups with and without early blood eosinophil increases up to 2 years. No differences in the dupilumab safety profile were observed in children with early eosinophil increases.
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