The effects of ivacaftor on CF fatty acid metabolism: An analysis from the GOAL study

Abstract

Background: Ivacaftor has produced significant improvement in certain individuals with cystic fibrosis (CF), though the full metabolic effects of treatment remain unknown. Abnormalities in fatty acid metabolism have previously been shown to be a characteristic of CFTR dysfunction. We hypothesized that as a reflection of this clinical improvement, ivacaftor would improve plasma fatty acid levels and decrease urine prostaglandin E metabolite levels.

Methods: This study analyzed plasma fatty acid levels and urine prostaglandin E metabolites (PGE-M) in 40 subjects with CF participating in the G551D observational (GOAL) study who demonstrated response to the medication by a significant decrease in sweat Cl levels. Paired samples were analyzed before and after 6months of ivacaftor treatment.

Results: Linoleic acid and docosahexaenoic acid levels, which are typically low in individuals with CF, did not significantly increase with ivacaftor treatment. However, arachidonic acid levels did decrease with ivacaftor treatment and there was a significant decrease in the arachidonic acid metabolite PGE-M as measured in the urine [median: before treatment 17.03ng/mg Cr; after treatment 9.06ng/mg Cr; p<0.001]. Furthermore, there were fatty acid age differences observed, including pediatric participants having significantly greater linoleic acid levels at baseline.

Conclusion: Ivacaftor reduces inflammatory PGE without fully correcting the plasma fatty acid abnormalities of CF. Age-related differences in fatty acid levels were observed, that may be a result of other clinical factors, such as diet, clinical care, or drug response.

Keywords: Cystic fibrosis; Fatty acids; Ivacaftor; Prostaglandin E.

Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1. Urine Prostaglandin E Metabolite (PGE-M) Analysis

(A) The change in urine PGE-M for all 40 participants before and after treatment with ivacaftor; p

Figure 2. Urine Prostaglandin E Metabolite (PGE-M) Levels by Age

(A) Baseline urine PGE-M by age. (B) The individual participant change in urine PGE-M after 6 months of ivacaftor treatment in the pediatric population (age