Nintedanib in children and adolescents with fibrosing interstitial lung diseases
Robin R. Deterding, Lisa R. Young, Emily M. DeBoer, David Warburton, Steve Cunningham, Nicolaus Schwerk, Kevin R. Flaherty, Kevin K. Brown, Mihaela Dumistracel, Elvira Erhardt, Julia Bertulis, Martina Gahlemann, Susanne Stowasser, Matthias Griese
Abstract
Background Childhood interstitial lung disease (ILD) comprises a spectrum of rare ILDs affecting infants, children and adolescents. Nintedanib is a licensed treatment for pulmonary fibrosis in adults. The primary objectives of the InPedILD trial were to determine the dose-exposure and safety of nintedanib in children and adolescents with fibrosing ILD. Methods Patients aged 6–17 years with fibrosing ILD on high-resolution computed tomography and clinically significant disease were randomised 2:1 to receive nintedanib or placebo for 24 weeks and then open-label nintedanib. Dosing was based on weight-dependent allometric scaling. Co-primary end-points were the area under the plasma concentration–time curve at steady state (AUC τ,ss ) at weeks 2 and 26 and the proportion of patients with treatment-emergent adverse events at week 24. Results 26 patients received nintedanib and 13 patients received placebo. The geometric mean (geometric coefficient of variation) AUC τ,ss for nintedanib was 175 µg·h·L −1 (85.1%) in patients aged 6–11 years and 167 µg·h·L −1 (83.6%) in patients aged 12–17 years. In the double-blind period, adverse events were reported in 84.6% of patients in each treatment group. Two patients discontinued nintedanib due to adverse events. Diarrhoea was reported in 38.5% and 15.4% of the nintedanib and placebo groups, respectively. Adjusted mean± se changes in percentage predicted forced vital capacity at week 24 were 0.3±1.3% in the nintedanib group and −0.9±1.8% in the placebo group. Conclusions In children and adolescents with fibrosing ILD, a weight-based dosing regimen resulted in exposure to nintedanib similar to adults and an acceptable safety profile. These data provide a scientific basis for the use of nintedanib in this patient population.