Impact of age at initiation of elexacaftor/tezacaftor/ivacaftor on pancreatic enzyme function in children with cystic fibrosis

Abstract

Objectives: Following the KIWI and ARRIVAL studies (Davies et al., 2016, 2019), which demonstrated some improvements in pancreatic enzyme levels among participants taking Ivacaftor, the Royal London Hospital (RLH) initiated annual faecal elastase (FE) monitoring for children under 12 years on cystic fibrosis transmembrane conductance regulator (CFTR) modulators at our Cystic Fibrosis (CF) centre. Method(s): FE was measured before starting Elexacaftor/Tezacaftor/Ivacaftor (ETI) and after 12 months of ETI in CF children aged 6-12 years under our care since 2022. Due to the small sample size, statistical analysis was not feasible. Data were categorized into three groups: no change, increase, or decrease in FE. Further analysis examined whether prior CFTR modulator use or age at initiation influenced pancreatic enzyme function. Result(s): Stool samples were collected from 96% of eligible patients, with one follow-up sample pending. The average age of starting ETI was 8.8 years, and 52% were male. FE percentage change from baseline to 12 months on ETI Although a 30% overall increase in FE was observed after 12 months on ETI, most levels remained below the threshold to discontinue pancreatic enzyme replacement therapy (PERT). Larger increases were noted in patients starting a CFTR modulator under 4 years of age. At birth, all were pancreatic insufficient, with 60% (n=3) having FE levels 200 mcg/g and discontinuing PERT. After 12 months on ETI, 80% (n=4) showed further increases, with 60% (n=3) now achieving FE >200 mcg/g and discontinuing PERT. Conclusion(s): Larger data sets are required to assess whether FE changes on CFTR modulators in children under 4 are statistically significant. Annual screening is recommended for this group to monitor pancreatic enzyme function. We await results from our 2-5-year-old cohort starting ETI in January 2024 to confirm these findings and will continue annual FE monitoring for children under 12. Copyright © 2025