Forced Expiratory Flow (FEF25-75%) as a Clinical Endpoint in Children and Adolescents with Symptomatic Asthma Receiving Tiotropium: A Post Hoc Analysis.

Stanley J Szefler,Branko Jugovic,Christian Vogelberg,Stanley Goldstein,Petra M Moroni-Zentgraf,Michael Engel,George W Bensch,Ralf Sigmund,Eckard H Hamelmann,John Given

doi:10.1007/s41030-020-00117-6

Abstract

IntroductionIn pediatric patients with asthma, measurements of forced expiratory volume in 1 s (FEV1) may be normal or may not correlate with symptom severity. Forced expiratory flow at 25–75% of the vital capacity (FEF25–75%) is a potentially more sensitive parameter for assessing peripheral airway function. This post hoc analysis compared FEF25–75% with FEV1 as an endpoint to assess bronchodilator responsiveness in children with asthma.MethodsChange from baseline in trough FEF25–75% and trough FEV1 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 FEF25–75% and FEV1 were calculated and analyzed.ResultsA total of 1590 patients were included in the analysis. Tiotropium Respimat® consistently improved FEF25–75% and FEV1 versus placebo, although in adolescents with severe asthma, the observed improvements were not statistically significant. Improvements in FEF25–75% response with tiotropium versus placebo were largely more pronounced than improvements in FEV1. Statistical assessment of the correlation of FEV1 and FEF25–75% showed moderate-to-high correlations (Pearson’s correlation coefficients 0.73–0.80).ConclusionsIn pediatric patients, FEF25–75% may be a more sensitive measure to detect treatment response, certainly to tiotropium, than FEV1 and should be evaluated as an additional lung function measurement.Electronic Supplementary MaterialThe online version of this article (10.1007/s41030-020-00117-6) contains supplementary material, which is available to authorized users.

Highlights

Change from baseline in troughFEF25–75% and trough forced expiratory volume in 1 s (FEV1) following treatment with either tiotropium (5 lg or 2.5 lg) or placebo RespimatÒ was analyzed in four phase III trials in children (aged 6–11 years) and adolescents (aged 12–17 years) with symptomatic moderate (VivaTinA-asthmaÒ and PensieTinAasthmaÒ) and mild (CanoTinA-asthmaÒ and RubaTinA-asthmaÒ) asthma
In pediatric patients with asthma, measurements of forced expiratory volume in 1 s (FEV1) may be normal or may not correlate with symptom severity
Using pooled data from four phase III trials in patients with asthma aged 6–17 years, we investigated change from baseline in trough FEF25–75% and FEV1 following treatment with either tiotropium (5 lg or 2.5 lg) or placebo RespimatÒ

Summary

Change from baseline in trough

FEF25–75% and trough FEV1 following treatment with either tiotropium (5 lg or 2.5 lg) or placebo RespimatÒ was analyzed in four phase III trials in children (aged 6–11 years) and adolescents (aged 12–17 years) with symptomatic moderate (VivaTinA-asthmaÒ and PensieTinAasthmaÒ) and mild (CanoTinA-asthmaÒ and RubaTinA-asthmaÒ) asthma. Tiotropium RespimatÒ (Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany) has been shown to improve different measures of lung function in clinical studies with both children and adolescents, including FEF25–75% [6,7,8,9] This is a post hoc analysis of four placebo-controlled trials in children and adolescents with symptomatic asthma who remained uncontrolled despite maintenance therapy (inhaled corticosteroids ± long-acting b2-agonist ± leukotriene receptor antagonist, Table 1). Across the trials in 6 to 11and 12 to 17-year-old patients with moderate/severe asthma, tiotropium Respimat consistently improved trough FEV1 (Fig. 1a) and trough FEF25–75% (Fig. 1b) versus placebo; in the PensieTinA-asthma study in adolescents with severe asthma, the observed improvements were not statistically significant, possibly due to a pronounced placebo response, which left little room for differentiation between the treatment groups [6]. Even though assessment of FEF25–75% is not currently recommended in asthma guidelines,

Allergic rhinitis

Symptomatic moderate asthma