Forced Expiratory Flow (FEF(25–75%)) as a Clinical Endpoint in Children and Adolescents with Symptomatic Asthma Receiving Tiotropium: A Post Hoc Analysis

INTRODUCTION: In pediatric patients with asthma, measurements of forced expiratory volume in 1 s (FEV(1)) may be normal or may not correlate with symptom severity. Forced expiratory flow at 25–75% of the vital capacity (FEF(25–75%)) is a potentially more sensitive parameter for assessing peripheral airway function. This post hoc analysis compared FEF(25–75%) with FEV(1) as an endpoint to assess bronchodilator responsiveness in children with asthma. METHODS: Change from baseline in trough FEF(25–75%) and trough FEV(1) following treatment with either tiotropium (5 µg or 2.5 µg) or placebo Respimat(®) was analyzed in four phase III trials in children (aged 6–11 years) and adolescents (aged 12–17 years) with symptomatic moderate (VivaTinA-asthma(®) and PensieTinA-asthma(®)) and mild (CanoTinA-asthma(®) and RubaTinA-asthma(®)) asthma. Data from all treatment arms were pooled and correlations between FEF(25–75%) and FEV(1) were calculated and analyzed. RESULTS: A total of 1590 patients were included in the analysis. Tiotropium Respimat(®) consistently improved FEF(25–75%) and FEV(1) versus placebo, although in adolescents with severe asthma, the observed improvements were not statistically significant. Improvements in FEF(25–75%) response with tiotropium versus placebo were largely more pronounced than improvements in FEV(1). Statistical assessment of the correlation of FEV(1) and FEF(25–75%) showed moderate-to-high correlations (Pearson’s correlation coefficients 0.73–0.80). CONCLUSIONS: In pediatric patients, FEF(25–75%) may be a more sensitive measure to detect treatment response, certainly to tiotropium, than FEV(1) and should be evaluated as an additional lung function measurement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s41030-020-00117-6) contains supplementary material, which is available to authorized users.