Abstract：
BACKGROUND: Uncontrolled asthma in growing children can impair lung growth that may lead to adverse complications in later life. Dupilumab, a human monoclonal antibody, blocks the shared receptor for IL-4 and IL-13, key drivers of type 2 inflammation.
OBJECTIVE: To extensively evaluate the effect of dupilumab on lung function in children (6-11 years) with moderate-to-severe asthma enrolled in phase 3 LIBERTY ASTHMA VOYAGE (NCT02948959).
METHODS: Children with asthma were randomized 2:1 to add-on dupilumab 100/200 mg by bodyweight or placebo every 2 weeks, for 52 weeks. We analyzed spirometry parameters in children with type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥20 parts per billion [ppb] at baseline) and within subgroups defined by baseline blood eosinophils or FeNO values.
RESULTS: A total of 116 (49%) dupilumab-treated children and 59 (52%) on placebo had impaired lung function (prebronchodilator percent-predicted forced expiratory volume in 1 second [ppFEV1] <80%) at baseline. Dupilumab improved pre- and postbronchodilator ppFEV1 as early as week 2, sustained for up to 52 weeks (least-squares mean difference vs placebo at week 52: 7.79 percentage points; 95% confidence interval [CI]: 4.36-11.22; P < .001 and 4.37 points; 95% CI: 0.95-7.78; P = .01, respectively). Sustained improvements were also observed in other lung function parameters, including pre- and postbronchodilator forced vital capacity (FVC), prebronchodilator forced expiratory flow, and FEV1/FVC ratio across all populations.
CONCLUSIONS: Dupilumab led to significant, sustained lung function improvements across a range of lung function measures in children (6-11 years) with uncontrolled, moderate-to-severe type 2 asthma.
OBJECTIVE: To extensively evaluate the effect of dupilumab on lung function in children (6-11 years) with moderate-to-severe asthma enrolled in phase 3 LIBERTY ASTHMA VOYAGE (NCT02948959).
METHODS: Children with asthma were randomized 2:1 to add-on dupilumab 100/200 mg by bodyweight or placebo every 2 weeks, for 52 weeks. We analyzed spirometry parameters in children with type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥20 parts per billion [ppb] at baseline) and within subgroups defined by baseline blood eosinophils or FeNO values.
RESULTS: A total of 116 (49%) dupilumab-treated children and 59 (52%) on placebo had impaired lung function (prebronchodilator percent-predicted forced expiratory volume in 1 second [ppFEV1] <80%) at baseline. Dupilumab improved pre- and postbronchodilator ppFEV1 as early as week 2, sustained for up to 52 weeks (least-squares mean difference vs placebo at week 52: 7.79 percentage points; 95% confidence interval [CI]: 4.36-11.22; P < .001 and 4.37 points; 95% CI: 0.95-7.78; P = .01, respectively). Sustained improvements were also observed in other lung function parameters, including pre- and postbronchodilator forced vital capacity (FVC), prebronchodilator forced expiratory flow, and FEV1/FVC ratio across all populations.
CONCLUSIONS: Dupilumab led to significant, sustained lung function improvements across a range of lung function measures in children (6-11 years) with uncontrolled, moderate-to-severe type 2 asthma.
摘要：
背景：在成长中的儿童中，未控制的哮喘会损害肺生长，这可能导致以后生活中的不良并发症。Dupilumab,一种人类单克隆抗体，阻断2型炎症的关键驱动因素IL-4和IL-13的共有受体。
目的：广泛评估dupilumab对3期哮喘患者（NCT02948959）中重度哮喘患儿（6-11岁）肺功能的影响。
方法：哮喘儿童被随机分为2：1，每2周按体重添加100/200mgdupilumab或安慰剂，52周我们分析了2型哮喘患儿(基线时血液嗜酸性粒细胞≥150个细胞/μL或部分呼出气一氧化氮[FeNO]≥10亿分之20[ppb])和基线血液嗜酸性粒细胞或FeNO值定义的亚组中的肺活量测定参数。
结果：基线时，共有116名（49％）接受dupilumab治疗的儿童和59名（52％）接受安慰剂治疗的儿童肺功能受损（支气管扩张剂前预测的1秒用力呼气量百分比[ppFEV1]<80％）。Dupilumab最早在第2周改善支气管扩张剂前和后ppFEV1，持续长达52周（52周时与安慰剂的最小二乘平均差：7.79个百分点；95％置信区间[CI]：4.36-11.22；P<.001和4.37点；95％CI：0.95-7.78；P=0.01，分别）。其他肺功能参数也观察到持续改善，包括支气管扩张剂前和后强制肺活量（FVC），支气管扩张剂前用力呼气流量，和所有人群的FEV1/FVC比率。
结论：Dupilumab导致显著，在一系列不受控制的儿童（6-11岁）的肺功能测量中，持续的肺功能改善，中度至重度2型哮喘。
目的：广泛评估dupilumab对3期哮喘患者（NCT02948959）中重度哮喘患儿（6-11岁）肺功能的影响。
方法：哮喘儿童被随机分为2：1，每2周按体重添加100/200mgdupilumab或安慰剂，52周我们分析了2型哮喘患儿(基线时血液嗜酸性粒细胞≥150个细胞/μL或部分呼出气一氧化氮[FeNO]≥10亿分之20[ppb])和基线血液嗜酸性粒细胞或FeNO值定义的亚组中的肺活量测定参数。
结果：基线时，共有116名（49％）接受dupilumab治疗的儿童和59名（52％）接受安慰剂治疗的儿童肺功能受损（支气管扩张剂前预测的1秒用力呼气量百分比[ppFEV1]<80％）。Dupilumab最早在第2周改善支气管扩张剂前和后ppFEV1，持续长达52周（52周时与安慰剂的最小二乘平均差：7.79个百分点；95％置信区间[CI]：4.36-11.22；P<.001和4.37点；95％CI：0.95-7.78；P=0.01，分别）。其他肺功能参数也观察到持续改善，包括支气管扩张剂前和后强制肺活量（FVC），支气管扩张剂前用力呼气流量，和所有人群的FEV1/FVC比率。
结论：Dupilumab导致显著，在一系列不受控制的儿童（6-11岁）的肺功能测量中，持续的肺功能改善，中度至重度2型哮喘。
