Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two F508del Alleles.
Am J Respir Crit Care Med
; 205(5): 540-549, 2022 03 01.
Article
in En
| MEDLINE
| ID: mdl-34936849
ABSTRACT
Rationale The CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to improve clinical outcomes and sweat chloride concentration 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 sweat chloride concentration, nasal potential difference, and intestinal current measurement before and 8-16 weeks after initiation of ELX/TEZ/IVA. Measurements and MainResults:
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, nasal potential difference and intestinal current measurement showed that ELX/TEZ/IVA improved CFTR function in nasal epithelia to a level of 46.5% (interquartile range [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 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. Clinical trial registered with www.clinicaltrials.gov (NCT04732910).Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cystic Fibrosis Transmembrane Conductance Regulator
/
Cystic Fibrosis
Type of study:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Am J Respir Crit Care Med
Journal subject:
TERAPIA INTENSIVA
Year:
2022
Document type:
Article
Affiliation country:
Alemania