Effects of Lumacaftor-Ivacaftor Therapy on Cystic Fibrosis Transmembrane Conductance Regulator Function in Phe508del Homozygous Patients with Cystic Fibrosis

The combination of the CFTR (cystic fibrosis transmembrane conductance regulator) corrector lumacaftor with the potentiator ivacaftor has been approved for the treatment of patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. The phase 3 trials examined clinical outcomes but did...

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Published in:American journal of respiratory and critical care medicine 2018-06, Vol.197 (11), p.1433-1442
Main Authors: Graeber, Simon Y, Dopfer, Christian, Naehrlich, Lutz, Gyulumyan, Lena, Scheuermann, Heike, Hirtz, Stephanie, Wege, Sabine, Mairbäurl, Heimo, Dorda, Marie, Hyde, Rebecca, Bagheri-Hanson, Azadeh, Rueckes-Nilges, Claudia, Fischer, Sebastian, Mall, Marcus A, Tümmler, Burkhard
Format: Article
Language:English
Subjects:
Biomarkers
Body mass index
Chloride
Clinical outcomes
Cystic fibrosis
FDA approval
Lung diseases
Mutation
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Summary:The combination of the CFTR (cystic fibrosis transmembrane conductance regulator) corrector lumacaftor with the potentiator ivacaftor has been approved for the treatment of patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. The phase 3 trials examined clinical outcomes but did not evaluate CFTR function in patients. To examine the effect of lumacaftor-ivacaftor on biomarkers of CFTR function in Phe508del homozygous patients with cystic fibrosis aged 12 years and older. This prospective observational study assessed clinical outcomes including FEV % predicted and body mass index, and CFTR biomarkers including sweat chloride concentration, nasal potential difference, and intestinal current measurement before and 8-16 weeks after initiation of lumacaftor-ivacaftor. A total of 53 patients were enrolled in the study, and 52 patients had baseline and follow-up measurements. After initiation of lumacaftor-ivacaftor sweat chloride concentrations were reduced by 17.8 mmol/L (interquartile range [IQR], -25.9 to -6.1; P 
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.201710-1983OC