Ultrashort echo time MRI can evaluate treatment effect of Lumacaftor/Ivacaftor

Abstract

Introduction/Aim: To evaluate feasibility of ultrashort echo time (UTE) MRI in a subset of patients aged 6-11 years with cystic fibrosis (CF) who were homozygous for the F508del mutation treated with lumacaftor (LUM) and ivacaftor (IVA) combination therapy in a phase 3 trial (NCT02514473). Methods: UTE MRI scans were obtained at study baseline (n=10); a second scan was completed at week 24 in 9 patients (4 LUM/IVA, 5 placebo) at 3 institutions using MRI hardware from 2 vendors. One vendor platform was 3D radial UTE1; the other was 3D “stack of stars” UTE.2 Scans were obtained during 5 minutes of tidal breathing without use of IV contrast. MRI scans were scored by 2 independent readers using the Brody score after supervised training on UTE MRI scans. Readers were blinded to time point and treatment arm. Scores are presented as mean ± SD; no statistical testing was performed. Results: Despite the lower image quality of MRI compared with CT, potential treatment effects were seen on UTE MRI. Mean total Brody score with treatment decreased from 41.1 to 32.5, a change from baseline (± SD; %) of 8.4±11.2 but increased from 31.3 to 34.6, a change from baseline of 3.3±8.2 with placebo. Mucus plugging subscore decreased by 5.0±5.1, from 8.5 to 3.5 with treatment but increased by 1.4±4.4 from 4.2 to 5.6 with placebo. There were no noticeable changes in other subscores (bronchiectasis, peribronchial thickening, parenchymal opacities, or hyperinflation). Conclusion: In this analysis from an exploratory substudy in patients with CF aged 6-11 years homozygous for F508del, UTE MRI was a feasible approach for detecting the effect of LUM/IVA, despite the small sample size, short duration of treatment, and limitations in image quality. As optimization of UTE MRI technology improves image quality, monitoring disease course in patients with CF may also improve.L6220913992018-05-16 <br />