WS20.2 Intra-patient variability of sweat chloride concentrations in patients with cystic fibrosis (CF)

Abstract

Introduction Sweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although we agree on a cut-of value to diagnose CF, we have only limited information on the natural variability of sweat chloride over time. Still, this information is useful for power calculations in clinical trials. Therefore, we analyzed sweat test results obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial. Methods In subjects with G551D at least 12 years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48 weeks. We explored 1062 pilocarpine sweat test values obtained in 78 patients. Results Mean overall sweat chloride value (all patients, all tests) was 100.1 mmol/L (95% CI 96.4–103.7). Using a random coefficient model, the within-subject standard deviation(SD) for sweat chloride was 8.5 mmol/L (95% CI 8.1–8.9) and between-subject SD was 9.8 mmol/L (95% CI 8.1–11.9). Standard deviations were similar with results from the left and from the right arm. Taking the mean measure of both arms rather than the result of one arm decreased within-subject SD by only 0.3 mmol/L. Conclusion Although the sweat test is considered a robust measure, sweat chloride measurements in patients with CF had an inherent biological variability that is higher than commonly considered. Further analyses of placebo arm data are crucial to learn more about the natural variability of outcome parameters.