Multi-center Study of Hyperpolarized Xenon MRI in Children with Cystic Fibrosis Following Initiation of CFTR Modulator Therapy (HyPOINT).

RATIONALE

Elexacaftor/tezacaftor/ivacaftor (ETI) has significantly improved lung function in people with cystic fibrosis (CF), prompting the need for outcome measures that can detect mild disease. In this new era of CFTR modulator therapy, more sensitive endpoints are required to evaluate the progression of early lung disease and to determine the efficacy of new CF therapies. Prior to the availability of highly effective therapies 129Xenon magnetic resonance imaging (Xe MRI) was shown to be more sensitive to regional ventilation changes compared to spirometry.

OBJECTIVES

To evaluate the longitudinal changes in pulmonary function and Xe-MRI outcomes after treatment with ETI in children and young people with CF.

METHODS

Lung function was assessed longitudinally at baseline 1, 6, and 12 months following ETI treatment initiation in children and young people with CF between the ages of 6 and 18 years at four study sites. Ventilation defect percentage (VDP), reader-defect percentage (RDP), Lung Clearance Index (LCI) and Forced Expiratory Volume in 1 second (FEV1) were reported.

MEASUREMENTS AND MAIN RESULTS

A total of 28 participants were enrolled; 25 completed at least baseline and one-month measurements. All four measures (RDP, VDP, LCI and FEV1) improved at one month after ETI initiation with a mean (standard deviation) absolute change of -1.2 (1.7) in LCI, 6.9 (12.3) in FEV1, -4.3 (4.8) in VDP and --7.8 (9.6) in RDP, respectively. Xe MRI outcomes (RDP and VDP) showed the largest relative treatment effects with mean relative improvements of 43% and 72%, respectively. One third of participants (8/25) had improvements in VDP and RDP but did not show improvements in FEV1.

CONCLUSIONS

Xe MRI captures sustained ventilation improvements following ETI initiation. Xe MRI metrics may provide a suitable endpoint for future interventional trials-particularly for people with CF with mild lung disease.