RATIONALE
We recently demonstrated that triple combination CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in airway and intestinal epithelia to 40 to 50% of normal in patients with cystic fibrosis (CF) with one or two F508del 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.
OBJECTIVES
To examine the effect of ELX/TEZ/IVA on LCI and lung MRI scores in patients with CF and one or two F508del alleles aged 12 years and older.
METHODS
This prospective, observational, multicenter, post-approval study assessed LCI and lung MRI scores before and 8-16 weeks after initiation of ELX/TEZ/IVA.
MEASUREMENTS AND MAIN RESULTS
A total of 91 patients with CF including 45 heterozygous for F508del and a minimal function mutation (MF) and 46 homozygous for F508del were enrolled in this study. Treatment with ELX/TEZ/IVA improved LCI in F508del/MF (-2.4;IQR, -3.7 - -1.1;P<0.001) and F508del homozygous (-1.4;IQR, -2.4 - -0.4;P<0.001) patients. Further, ELX/TEZ/IVA improved the MRI global score in F508del/MF (-6.0;IQR, -11.0 - -1.3;P<0.001) and F508del homozygous (-6.5;IQR, -11.0 - -1.3;P<0.001) patients.
CONCLUSIONS
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 F508del alleles in a real-world, post-approval setting.