Role of elexacaftor-tezacaftor-ivacaftor therapy on fecal elastase-1 and fat-soluble vitamins in children with cystic fibrosis.

Clinical studies have shown that Elexacaftor-Tezacaftor-Ivacaftor (ETI) improves lung disease and body weight in individuals with cystic fibrosis (CF); however, gastrointestinal system effects remain unclear. The purpose of this study was to evaluate exocrine pancreatic function using fecal elastase-1 (FE-1) levels in CF patients receiving ETI therapy and to assess changes in fat-soluble vitamin levels specifically within the pancreatic-insufficient (PI) subgroup. We retrospectively evaluated FE-1 levels before and during ETI treatment in the entire study group. Additionally, sweat chloride levels and growth parameters were assessed before and after follow-up ETI therapy in the entire study group. Also, vitamin A, D, E, PT, and INR levels were evaluated in PI patients before and after follow-up ETI treatment. The study included 20 pediatric CF patients with baseline FE-1 values. PI was present in 18 patients. The median age at the start of ETI therapy was 9.5 years (IQR 7.7-13.5; range 3-21 years). The median time between the baseline FE-1 test and the last FE-1 test was 12.0 months (IQR 12.0-19.5). The median FE-1 value before ETI therapy was 20.6 mcg/g (IQR 20.6-31.9), and after follow-up, 20.6 mcg/g (IQR 20.6-32.5) in 18 PI patients. Both PS patients maintained FE-1 levels ≥ 200 mcg/g before and after follow-up on ETI therapy. A significant increase in vitamin A levels was observed in PI patients, with a mean rise of 122.8 µg/L (p = 0.016). No significant change was observed in vitamin E levels (mean change 0.63 ± 4.14 µg/L; p = 0.304).

Conclusion

In our study, no significant improvement in FE-1 levels was observed in pediatric CF patients receiving ETI therapy, whereas a substantial increase in vitamin A levels was found in patients with PI. These findings suggest that the effect of ETI therapy on pancreatic function may be limited and that its impact on exocrine pancreatic function should be further investigated. What is Known: • Exocrine pancreatic insufficiency is common in cystic fibrosis and is typically assessed using fecal elastase-1 (FE-1). • CFTR modulator therapies, especially ETI, improve respiratory and nutritional outcomes by targeting CFTR function, but their impact on pancreatic exocrine function in pediatric patients remains unclear. C What is New: • In this real-life pediatric cohort, no significant increase in FE-1 levels was observed during ETI treatment. • Despite improvements in CFTR function and nutritional status, these changes were not accompanied by recovery of pancreatic exocrine function.