A-340 CFTR Modulator Therapy Increases Serum/Plasma Concentrations of Vitamin a in People with Cystic Fibrosis

Abstract

Abstract Introduction Pancreatic insufficiency (PI) is common in people with Cystic Fibrosis (PwCF), contributing to malabsorption of fat and fat-soluble vitamins. Thus, PI PwCF are prescribed pancreatic enzyme replacement therapy (PERT) and supplementation with fat-soluble vitamins. The circulating vitamin levels are monitored to guide dietary therapy. Currently, there are multiple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies available that have shown significant improvements in pulmonary function, anthropometric parameters, and life expectancy in PwCF, but the effects on serum/plasma fat-soluble vitamin levels remain unknown. The goal of this study was to determine how modulator therapy affects serum/plasma vitamin A and E levels in individuals with CF. Methods The analysis included 1139 serum/plasma samples from 157 children and adolescents with CF: 74 males, 83 females, between the ages of 2–17 years. Most individuals were homozygous or compound heterozygous for the F508del variant (n = 81 and n = 72, respectively). 141 individuals (90%) were diagnosed with PI (fecal elastase <200 μg/g stool). 76 individuals (48%) received different CFTR modulator therapies for at least 1 month. Vitamin A (retinol and retinyl palmitate) and Vitamin E (α-tocopherol and γ-tocopherol) were measured using a high-performance liquid chromatography assay. Data analyses were performed in Prism software (La Jolla, CA), and statistical significance was defined as P < 0.05. The study was approved by the IRB. Results Overall, vitamin deficiency was rarely observed in PwCF prescribed PERT and vitamin supplements; <3% of them had low concentrations of Vitamin A and/or E. The proportion of individuals with Vitamin A and/or E above the reference range was larger; 10.9% and 30.8% for Vitamin A and E, respectively, most likely reflecting supplementation. There was no correlation of plasma vitamin A or E results with sex, weight-for-age, height-for-age, or BMI-for-age. However, pancreatic status affected vitamin levels in individuals not taking modulators: samples from PI PwCF (n = 367) had significantly lower Vitamin A and E than those from PS PwCF (n = 71). In contrast, we have observed higher concentrations of Vitamin A retinol in individuals on modulators: 0.49 ± 0.13 mg/L on modulators vs 0.43 ± 0.12 mg/L without modulators. Pairwise analysis of samples from 76 individuals before and after modulator therapy confirmed this finding, showing an average 16% increase in serum/plasma retinol concentration (P < 0.0001). No changes in retinol were observed between different measurements in PwCF who were not taking modulators (n = 82). Vitamin E levels were not impacted by modulator therapy. Conclusions Advances in clinical care improved fat-soluble vitamin status in people with CF. However, even when supplemented and on PERT, PI PwCF not on modulators tend to have lower fat-soluble vitamin concentrations than PS PwCF. CFTR modulator therapy increases serum/plasma concentrations of vitamin A. Thus, individuals receiving modulators and vitamin supplementation should be monitored to avoid Vitamin A toxicity. This is especially true for PS PwCF who already have higher baseline vitamin levels.