WS12.03Changes in faecal pancreatic elastase in children with cystic fibrosis after 6 months of elexacaftor/tezacaftor/ivacaftor: results from the BEGIN study

Abstract

Objectives

Many children with CF (CwCF) have Exocrine Pancreatic Insufficiency (EPI) at birth, causing malnutrition and impaired growth. While EPI is often considered irreversible, studies of CwCF treated with ivacaftor demonstrated significantly increased faecal elastase (FE), indicating improvement in EPI. In contrast, FE did not change in adults with the severe F508del mutation treated with elexacaftor/tezacaftor/ivacaftor (ETI) in the PROMISE study. It remains unknown if those differences were due to the milder mutations or younger age of participants in ivacaftor versus ETI studies. We measured FE during BEGIN, a multi-center, prospective observational study of CwCF and ETI.

Methods

Paired faecal samples (n=150) were collected before and 6mo after initiating ETI from CwCF 2-5y (n=75) participating in BEGIN (28 F508del heteroz., 47 homoz.; mean age 4.1y at baseline). FE was measured with a FE-1 ELISA approved for clinical use, categorizing participants by manufacturer's recommendations (severe PI, FE<100 µg/g; mild-moderate PI, 100-200; normal, >200). Paired t-tests compared mean FE pre- and post-ETI; p-values less than 5% were considered significant.

Results

Mean FE increased significantly from baseline to 6 months (from 95 to 125 µg/mL, p=0.002). 8 CwCF (11%) had increases in FE sufficient to change clinical category, including 2 who improved from “severe insufficiency” to “mild to moderate”, 2 from “severe” to “normal”, and 4 from “mild to moderate” to “normal”. By comparison, 3 CwCF (4%) had decreased FE to a worsening clinical category. There was no impact of baseline age on FE change (p=0.27); in contrast, CwCF homozygous for F508del had smaller mean improvements (1.7-fold increase in FE) compared to heterozygotes (4.4-fold increase) (p=0.03).

Conclusions

FE significantly improved for 11% CwCF after 6 mo of ETI therapy, and clinical EPI status normalized for 8% of CwCF. Our findings suggest PI may be partially reversible for some young CwCF with ETI.