Impact of Elexacaftor/Tezacaftor/Ivacaftor on Fecal Elastase-1 in Children With Cystic Fibrosis.

Abstract

Background: Prior studies have documented improvement in pancreatic status after ivacaftor and lumacaftor/ivacaftor in a small number of patients with cystic fibrosis (CF). There is paucity of data with similar improvement after initiation of elexacaftor/tezacaftor/ivacaftor (ETI).

Methods: In this cross-sectional study, we retrospectively reviewed the change in fecal elastase-1 (FE-1) at least 6 months after initiation of ETI in children less than 12 years of age. Children who demonstrated a change in FE-1 of ≥ 100 µg/g from the baseline after ETI therapy (post-ETI FE-1 minus pre-ETI FE-1) were termed as responders and those with a change in FE-1 < 100 µg/g post-ETI (or no change in FE-1) were termed as nonresponders.

Results: Thirty-five children had post-ETI FE-1 value at least 6 months after its initiation and were included for final review. The mean change (±SD) in FE-1 post-ETI from the baseline in the entire cohort was 47.2 ± 89.5. Seven children had a change in FE-1 of ≥ 100 µg/g or more post-ETI (responders). Two of these seven patients had a change in FE-1 of ≥ 200 µg/g post-ETI. Twenty-three had no change or change < 100 µg/g post-ETI (nonresponders). Another five children who did not have a baseline FE-1 and had post-ETI FE-1 < 10 µg/g were also added to the nonresponders cohort increasing the total number to 28. The pre- and post-ETI body mass index was significantly higher in the responder group compared to the nonresponders.

Conclusion: In our cohort of 35 children, 7 (20%) were noted to have a positive change in FE-1 from the baseline value of ≥ 100 µg/g post-ETI. Further prospective multicenter studies will help identify predictive factors associated with improvement in FE-1 after initiation of CFTR-directed modulator therapies.