Introduction of Ivacaftor/Lumacaftor in Children With Cystic Fibrosis Homozygous for F508del in the Netherlands: A Nationwide Real-Life Study

Introduction: Lumacaftor/ivacaftor (lum/iva) was introduced in the Netherlands in 2017. We investigated 1-year efficacy of lum/iva on lung function and small airway and structural lung disease evaluated by multiple breath nitrogen washout and CT scan. Additionally, we investigated effects of lum/iva on exacerbations, anthropometry, sweat chloride and safety in children with CF in the Netherlands. Methods: Children with CF aged 6−18 years and homozygous for F508del treated in one of the seven Dutch CF centers for at least 12 months were eligible. Data were extracted from the Dutch CF Registry and electronic patient records. Primary outcome was change in percent predicted FEV₁ (ppFEV₁) after 12 months. Results: Nationwide, 247 children with CF were eligible for lum/iva. Eight patients discontinued lum/iva due to side effects. In total, 223/247 children (90.3%) were evaluated. Mean (range) age at baseline was 11.0 (6.0−17.1) years. There was no change in FEV₁ after 12 months of lum/iva. In a subgroup, markers of small airway function and structural lung disease, such as LCI (n = 28), mean change (SD) −10.0% (15.8), and bronchus-artery (BA) analysis on CT scan (n = 81), showed significant improvement (p < 0.01). Moreover, BMI (n = 192), exacerbations (n = 219) and sweat chloride measurements (n = 105) improved. Conclusion: Lum/iva was generally well tolerated in a real-life, nationwide pediatric cohort. The efficacy of lum/iva was comparable to phase 3 studies in children. LCI and BA analysis as markers of small airway and structural lung disease showed significant improvement which indicates the importance of these parameters to evaluate treatment effects of CF modulators in children.