Long-term effects of lumacaftor/ivacaftor on lung abnormalities detected by magnetic resonance imaging in children with cystic fibrosis

Background In a previous trial, magnetic resonance imaging (MRI) showed stabilisation of structural and functional lung abnormalities in children with cystic fibrosis (CF) after up to 96 weeks of Lumacaftor/Ivacaftor (LUM/IVA) therapy. However, real-world evidence on long-term effects in preschool and school-age children is limited. Methods Forty-nine children with CF homozygous for F508del (mean age 5.0 ± 3.5years, range 1-12years) underwent chest MRI before (MRI1) and annually up to four years on LUM/IVA (MRI2-5, mean 3.5 ± 1.1 examinations; mean follow-up 2.6 ± 1.1years). Treatment effects were evaluated using the chest MRI score, lung clearance index (LCI) and percent predicted forced expiratory volume in one second (ppFEV1). Results MRI global and morphology scores significantly decreased from MRI1 to MRI2 (15.9 ± 6.8 vs. 13.7 ± 6.5, p < 0.05; and 11.6 ± 4.8 vs. 10.6 ± 4.8, p < 0.05, respectively), while MRI perfusion score showed a non-significant decrease (4.7 ± 2.7 vs. 3.7 ± 2.6, p = 0.200). From MRI2 through MRI5, MRI global and perfusion scores remained stable ( p = 0.308–0.999), whereas MRI morphology score increased at MRI4 and MRI5 to the level of MRI1 ( p = 0.990 and p = 0.999 vs. MRI1). LCI was stable between MRI1 and MRI2 (9.0 ± 2.4 vs. 8.2 ± 2.2, p = 0.253) and was lower from MRI3 onward compared to MRI1 ( p < 0.05), while ppFEV1 was stable ( p = 0.355–0.999). Improvements in MRI global score between MRI1 and MRI2 correlated with improvements in LCI ( r = 0.42, p < 0.05). Conclusions Longitudinal chest MRI demonstrates initial improvement and second-year stabilization of morphological and functional lung abnormalities in preschool and school-age children with CF homozygous for F508del under LUM/IVA therapy, with increasing morphological abnormalities toward pre-treatment levels during the third year of therapy.