The Impact of Elexacaftor/Tezacaftor/Ivacaftor on Fat-Soluble Vitamin Status and Supplementation in a Paediatric 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 cohort study of children with CF. Data collected included demographics, clinical characteristics, lung function, respiratory colonisation, 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 from 77nmol/L to 85nmol/L (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 demonstrates ETI initiation increases vitamin D levels and lowers the requirement for fat-soluble vitamins supplementation. Whilst ETI did not cause significant increases in vitamin A and E, it appears there was a shift in vitamin A making supplementation more effective on ETI therapy.