RATIONALE
The CFTR modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to improve clinical outcomes and sweat chloride concentration (SCC) in patients with cystic fibrosis (CF) and one or two F508del alleles. However, the effect of ELX/TEZ/IVA on CFTR function in the airways and intestine has not been studied.
OBJECTIVES
To assess the effect of ELX/TEZ/IVA on CFTR function in airway and intestinal epithelia in patients with CF and one or two F508del alleles aged 12 years and older.
METHODS
This prospective observational multicenter study assessed clinical outcomes including FEV1 %predicted and body mass index, and the CFTR biomarkers SCC, nasal potential difference (NPD) and intestinal current measurement (ICM) before and 8-16 weeks after initiation of ELX/TEZ/IVA.
MEASUREMENTS AND MAIN RESULTS
A total of 107 patients with CF including 55 patients with one F508del and a minimal function mutation and 52 F508del homozygous patients were enrolled in this study. In patients with one F508del allele, NPD and ICM showed that ELX/TEZ/IVA improved CFTR function in nasal epithelia to a level of 46.5% (IQR, 27.5-72.4; P<0.001) and in intestinal epithelia to 41.8% of normal (IQR, 25.1-57.6; P<0.001). In F508del homozygous patients, ELX/TEZ/IVA exceeded improvement of CFTR function observed with TEZ/IVA and increased CFTR-mediated Cl- secretion to a level of 47.4% of normal (IQR, 19.3-69.2; P<0.001) in nasal and to 45.9% (IQR, 19.7-66.6; P<0.001) in intestinal epithelia.
CONCLUSIONS
Treatment with ELX/TEZ/IVA results in effective improvement of CFTR function in airway and intestinal epithelia in patients with CF and one or two F508del alleles.