The Impact of Elexacaftor/Tezacaftor/Ivacaftor on Fat‐Soluble Vitamin Status and Supplementation in a Pediatric Cystic Fibrosis Cohort

BACKGROUND: Children with Cystic Fibrosis (CF) are at risk of fat-soluble vitamin deficiencies, studies have shown Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy to substantially improve nutritional status. This study aimed to investigate the effect of ETI on fat-soluble vitamin levels A, D, and E, for children aged 6-16 years with CF. METHOD: We performed a retrospective pre-post study of children with CF. Data collected included demographics, clinical characteristics, serum Vitamin A, D and E and vitamin supplementation dosages. Seven timepoints were decided for statistical analysis: T1-T3-pre-ETI and T4-T7-at 6 month intervals post-ETI. The significance of changes in vitamin levels and supplementation was assessed using a linear mixed-effects model. A p-value < 0.05 was used to indicate significance. RESULTS: Fifty-six children met the inclusion criteria, with 262, 257, and 252 complete observations for Vitamins A, D, and E, respectively. Median Vitamin D levels increased following ETI initiation (p < 0.001). There was no significant increase in median Vitamin A levels however post-ETI there was a significant association between supplementation dose and serum Vitamin A levels (p = 0.008). There were no significant changes in median Vitamin E. Over the timepoints there was an increase in the proportion of patients receiving no vitamin supplementation. CONCLUSIONS: This study found following ETI initiation vitamin D levels increased, and the requirement for fat-soluble vitamin supplementation appeared to decrease. Whilst ETI was not associated with increased Vitamin A and E, the burden of supplementation decreased, and Vitamin A supplementation maybe more effective.