Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves clinical outcomes in people with cystic fibrosis (pwCF). In adult pwCF, fixed standard ETI dosing is usually used. Data on dose-response relationship are lacking.
In this pilot study we aimed to determine before-dose plasma concentrations of elexacaftor (ELX), tezacafor (TEZ) and ivacaftor (IVA) in adult pwCF, and evaluate whether they correlate with the clinical effect of ETI. Before-dose plasma concentrations were measured in adult pwCF as a part of ETI treatment follow-up at 6 months after starting the ETI treatment, using the in-house method of chromatography-mass spectrometry. BMI and FEV1 were recorded at baseline, 3 months and 6 months after starting the ETI treatment. Spearman test was used for correlation analyses.
This pilot cohort included four female and three male pwCF (n=7). Median age was 33 years (Q1=22; Q3=55). Median concentration of IVA was 0,73 ug/mL (Q1=0,05; Q3=0,89), TEZ was 1,20 ug/mL (Q1=0,24; Q3=2,90), and ELX was 3,40 ug/mL (Q1=0,34; Q3=7,30). IVA, TEZ and ELX concentrations were intercorrelated and were positively correlated with height and weight of pwCF at 6 months after starting the treatment. IVA and ELX concentrations were positively correlated with the pwCF’s weight at baseline, but did not correlate with changes in BMI. TEZ concentration was positively correlated with change in FEV1 (L) at 3 months and with change in FEV1 (% predicted) at 6 months after starting the treatment. This pilot study indicates that plasma IVA, TEZ and ELX concentrations might be dependent on weight and height of pwCF and there may be a dose-response relationship between TEZ and change in FEV1.