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.
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。