Real-world pancreatic function recovery and fluctuation in young children with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor.

Background: Clinical trials showed improved faecal elastase (FE-1) levels in younger children with cystic fibrosis (cwCF) on elexacaftor/tezacaftor/ivacaftor (ETI). Lower sweat chloride has been linked to better clinical outcomes in people with CF. Our previous work showed increased vitamin A levels in cwCF aged 5-15 years. We aimed to evaluate changes in FE-1 and vitamin levels and explore associations between sweat chloride and FE-1, in 2-6-year-olds starting ETI in a real-world setting.

Methods: In a large UK paediatric specialist CF centre, cwCF newly eligible for ETI when UK licensing age decreased to 2 years were included. Baseline vitamin A, D, E and FE-1 levels were collected retrospectively. Post ETI, FE-1, vitamin and sweat chloride levels were collected prospectively.

Results: 51/68 eligible patients were included. Median age on starting ETI was 4.1 (range 2.0-6.5) years. 12/43 (28 %) of pancreatic insufficient (PI) patients became pancreatic sufficient (PS) 6 months after ETI (p = 0.0005); 3 reverted to PI by 12 months, and 1 other patient became PS by 12 months. Enzymes were reduced or stopped for most children who became PS. Change in FE-1 negatively correlated with post ETI sweat chloride level (Spearman's ρ -0.49, p = 0.007). There was a significant increase in median vitamin D levels (p = 0.007) but no significant changes in vitamins A or E; particularly, high vitamin A levels were not seen.

Conclusions: Reversal of PI appears possible in preschool cwCF, but may not be sustained. Enzyme adjustments should be made cautiously, and monitoring of symptoms and FE-1 continued.