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:We sought to evaluate long-term efficacy and safety of dupilumab in children 6 to 11 years old 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 FEV1 and z score, 5-item Asthma Control Questionnaire-Interviewer Administered (ACQ-5-IA) score, fractional exhaled nitric oxide, 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 children who had been receiving dupilumab. Improvements in percent predicted FEV1 and z score, questionnaire score, fractional exhaled nitric oxide, and total IgE were observed in children with and without early blood eosinophil increases. No safety differences were observed across subgroups. CONCLUSION:Dupilumab 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 dupilumab safety profile were observed in children with early eosinophil increases. CLINICAL TRIAL REGISTRATION:VOYAGE: ClinicalTrials.gov Identifier: NCT02948959; EXCURSION: ClinicalTrials.gov Identifier: NCT03560466.
原文链接
分享
引用
