Nintedanib in children and adolescents with fibrosing interstitial lung diseases

Abstract

BackgroundChildhood 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.MethodsPatients 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 (AUCτ,ss) at weeks 2 and 26 and the proportion of patients with treatment-emergent adverse events at week 24.Results26 patients received nintedanib and 13 patients received placebo. The geometric mean (geometric coefficient of variation) AUCτ,ssfor nintedanib was 175 µg·h·L−1(85.1%) in patients aged 6–11 years and 160 µg·h·L−1(82.7%) 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±sechanges 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.ConclusionsIn 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.