Association of CFTR activity in sweat test, NPD, and ICM with ivacaftor and lumacaftor serum levels in Phe508del homozygous patients with cystic fibrosis

Combination therapy with the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) corrector lumacaftor and the CFTR potentiator ivacaftor has demonstrated significant impact on clinical parameters in Phe508del homozygous people with CF. Whether these changes under treatment are correlated to serum levels of both drugs had yet to be investigated. We therefore analyzed data from our previous study (OrkambiFacts, ClinicalTrials.gov Identifier: NCT02807415). In summary, we did not find statistically significant correlations between serum drug levels and changes in clinical parameters and biomarkers of CFTR function such as FEV1, BMI, sweat chloride, nasal potential difference (NPD) and intestinal current measurement (ICM). Absolute blood levels of lumacaftor or ivacaftor do not seem to be informative biomarkers to predict clinical improvement or the attenuation of the basic defect.