Cover Image

Effects of Elexacaftor/Tezacaftor/Ivacaftor therapy on CFTR function in patients with cystic fibrosis and one or two F508del alleles

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 ef...

Full description

Saved in:
Bibliographic Details
Main Authors: Gräber, Simon Y. (Author) , Vitzthum, Constanze (Author) , Pallenberg, Sophia T. (Author) , Naehrlich, Lutz (Author) , Stahl, Mirjam (Author) , Rohrbach, Alexander (Author) , Drescher, Marika (Author) , Minso, Rebecca (Author) , Ringshausen, Felix C. (Author) , Rueckes-Nilges, Claudia (Author) , Klajda, Jan (Author) , Berges, Julian (Author) , Yu, Yin (Author) , Scheuermann, Heike (Author) , Hirtz, Stephanie (Author) , Sommerburg, Olaf (Author) , Dittrich, Anna-Maria (Author) , Tümmler, Burkhard (Author) , Mall, Marcus A. (Author)
Format: Article (Journal)
Language:English
Published: March 1 2022
In: American journal of respiratory and critical care medicine
Year: 2022, Volume: 205, Issue: 5, Pages: 540-549
ISSN:1535-4970
DOI:10.1164/rccm.202110-2249OC
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1164/rccm.202110-2249OC
Verlag, lizenzpflichtig, Volltext: https://www.atsjournals.org/doi/10.1164/rccm.202110-2249OC
Get full text
Author Notes:Simon Y. Graeber, Constanze Vitzthum, Sophia T. Pallenberg, Lutz Naehrlich, Mirjam Stahl, Alexander Rohrbach, Marika Drescher, Rebecca Minso, Felix C. Ringshausen, Claudia Rueckes-Nilges, Jan Klajda, Julian Berges, Yin Yu, Heike Scheuermann, Stephanie Hirtz, Olaf Sommerburg, Anna-Maria Dittrich, Burkhard Tümmler, Marcus A. Mall
Description
Summary: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 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, 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).
Item Description:Gesehen am 07.06.2022
Physical Description:Online Resource
ISSN:1535-4970
DOI:10.1164/rccm.202110-2249OC

Similar Items