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