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

• Verfasst von: Gräber, Simon Y. [VerfasserIn]
• Verfasst von: Vitzthum, Constanze [VerfasserIn]
• Verfasst von: Pallenberg, Sophia T. [VerfasserIn]
• Verfasst von: Naehrlich, Lutz [VerfasserIn]
• Verfasst von: Stahl, Mirjam [VerfasserIn]
• Verfasst von: Rohrbach, Alexander [VerfasserIn]
• Verfasst von: Drescher, Marika [VerfasserIn]
• Verfasst von: Minso, Rebecca [VerfasserIn]
• Verfasst von: Ringshausen, Felix C. [VerfasserIn]
• Verfasst von: Rueckes-Nilges, Claudia [VerfasserIn]
• Verfasst von: Klajda, Jan [VerfasserIn]
• Verfasst von: Berges, Julian [VerfasserIn]
• Verfasst von: Yu, Yin [VerfasserIn]
• Verfasst von: Scheuermann, Heike [VerfasserIn]
• Verfasst von: Hirtz, Stephanie [VerfasserIn]
• Verfasst von: Sommerburg, Olaf [VerfasserIn]
• Verfasst von: Dittrich, Anna-Maria [VerfasserIn]
• Verfasst von: Tümmler, Burkhard [VerfasserIn]
• Verfasst von: Mall, Marcus A. [VerfasserIn]
• Titel: Effects of Elexacaftor/Tezacaftor/Ivacaftor therapy on CFTR function in patients with cystic fibrosis and one or two F508del alleles
• Verf.angabe: 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
• E-Jahr: 2022
• Jahr: March 1 2022
• Umfang: 10 S.
• Fussnoten: Gesehen am 07.06.2022
• Titel Quelle: Enthalten in: American journal of respiratory and critical care medicine
• Ort Quelle: New York, NY : American Thoracic Society, 1959
• Jahr Quelle: 2022
• Band/Heft Quelle: 205(2022), 5, Seite 540-549
• ISSN Quelle: 1535-4970
• DOI: doi:10.1164/rccm.202110-2249OC
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CFTR biomarker
• Sach-SW: cystic fibrosis
• Sach-SW: elexacaftor/tezacaftor/ivacaftor
• Sach-SW: intestinal current measurement
• Sach-SW: nasal potential difference
• K10plus-PPN: 180609908X

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. - - Clinical trial registered with www.clinicaltrials.gov (NCT04732910).