Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two Alleles.

We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in airway and intestinal epithelia to 40-50% of normal in patients with cystic fibrosis (CF) with one or two alleles. In previous studies, this improvement of CFTR function was shown to improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout and abnormalities in lung morphology and perfusion detected by magnetic resonance imaging (MRI) have not been studied. To examine the effect of ELX/TEZ/IVA on LCI and lung MRI scores in patients with CF and one or two alleles aged ⩾12 years. This prospective, observational, multicenter, postapproval study assessed LCI and lung MRI scores before and 8-16 weeks after initiation of ELX/TEZ/IVA. A total of 91 patients with CF, including 45 heterozygous for and a minimal function mutation (MF) and 46 homozygous for , were enrolled in this study. Treatment with ELX/TEZ/IVA improved LCI in /MF (-2.4; interquartile range [IQR], -3.7 to -1.1;  < 0.001) and homozygous (-1.4; IQR, -2.4 to -0.4;  < 0.001) patients. Furthermore, ELX/TEZ/IVA improved the MRI global score in /MF (-6.0; IQR, -11.0 to -1.3;  < 0.001) and homozygous (-6.5; IQR, -11.0 to -1.3;  < 0.001) patients. Our data demonstrate that improvement of CFTR function by ELX/TEZ/IVA improves lung ventilation and abnormalities in lung morphology, including airway mucus plugging and wall thickening, in adolescent and adult patients with CF and one or two alleles in a real-world, postapproval setting. Clinical trial registered with www.clinicaltrials.gov (NCT04732910).