Journalartikel

Jahr der Veröffentlichung: 2022

Seiten: 540-549

Zeitschrift: American Journal of Respiratory and Critical Care Medicine

Bandnummer: 205

Heftnummer: 5

ISSN: 1073-449X

eISSN: 1535-4970

DOI Link: https://doi.org/10.1164/rccm.202110-2249OC

Verlag: American Thoracic Society

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 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.

Harvard-Zitierstil: Graeber, S., Vitzthum, C., Pallenberg, S., Naehrlich, L., Stahl, M., Rohrbach, A., et al. (2022) Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two F508del Alleles, American Journal of Respiratory and Critical Care Medicine, 205(5), pp. 540-549. https://doi.org/10.1164/rccm.202110-2249OC

APA-Zitierstil: Graeber, S., Vitzthum, C., Pallenberg, S., Naehrlich, L., Stahl, M., Rohrbach, A., Drescher, M., Minso, R., Ringshausen, F., Rueckes-Nilges, C., Klajda, J., Berges, J., Yu, Y., Scheuermann, H., Hirtz, S., Sommerburg, O., Dittrich, A., Tuemmler, B., & Mall, M. (2022). Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two F508del Alleles. American Journal of Respiratory and Critical Care Medicine. 205(5), 540-549. https://doi.org/10.1164/rccm.202110-2249OC