Nintedanib in children and adolescents with fibrosing interstitial lung diseases.
Eur Respir J
; 61(2)2023 02.
Article
em En
| MEDLINE
| ID: mdl-36041751
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 6-17â years with fibrosing ILD on high-resolution computed tomography and clinically significant disease were randomised 21 to receive nintedanib or placebo for 24â 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.RESULTS:
26 patients received nintedanib and 13 patients received placebo. The geometric mean (geometric coefficient of variation) AUCτ,ss for nintedanib was 175â µg·h·L-1 (85.1%) in patients aged 6-11â years and 160â µg·h·L-1 (82.7%) in patients aged 12-17â 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Pulmonares Intersticiais
/
Fibrose Pulmonar Idiopática
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
/
Adult
/
Child
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article