Effect of lumacaftor/ivacaftor on ct scores: Exploratory imaging substudy

Abstract

Introduction/Aim: To evaluate lumacaftor (LUM) and ivacaftor (IVA) combination therapy on lung morphology with CT scanning in patients aged 6-11 years with cystic fibrosis (CF) homozygous for the F508del- CFTR mutation. Methods: Baseline CT scans were obtained in 19 patients (12 LUM/ IVA, 7 placebo) from the phase 3 trial (NCT02514473), and 24-week CT scans were completed in 7 active treatment and 3 placebo patients. CT scans were obtained at total lung capacity and at residual volume (RV). CT scans were scored by 2 independent readers blinded to all patient and time point information using the Brody score, which evaluates extent and severity of multiple aspects of CF lung disease, including bronchiectasis and air trapping. Scores are presented as mean ± SD; no statistical testing was performed for this preliminary study. Results: Mean total CT score (sum of the subcomponent scores) decreased from 20.6 to 12.5 (mean change ± SD, 8.1±13.6) in the LUM/IVA group and increased from 32.8 to 41.4 (8.6±14.6) in the placebo group. Mean bronchiectasis score decreased from 3.2 to 2.5 (0.7±1.3) in the LUM/IVA group and increased from 6.4 to 8.1 (1.7±2.1) in the placebo group. Additionally, there was a suggestion that several ectatic bronchi decreased in size in patients on active treatment. Mean air trapping score decreased from 7.8 to 5.9 (1.9±6.8) in the active group and increased from 9.8 to 14.5 (4.7±11.7) in the placebo group. Conclusion: This is the first report to describe CT lung findings after CFTR corrector/potentiator therapy in patients 6-11 years of age homozygous for F508del. In this 24-week exploratory analysis, bronchiectasis and air trapping scores improved in patients treated with LUM/IVA and worsened in the placebo group. These data suggest that LUM/IVA may reduce CF disease-related changes in lung morphology and support the need for further study.L6220918172018-05-16 <br />