EPS5.03 Elexacaftor/Tezacaftor/Ivacaftor for 76 weeks is associated with a reduced orocaecal transit time: the GIFT-CF3 extension study

Background and objectives: The effect of elexacaftor/tezacaftor/ivacaftor (ETI) on the gut in cystic fibrosis (CF) is currently unknown. The GIFT-CF3 study (NCT04618185), a prospective cohort study, has used MRI to compare gastrointestinal (GI) function before, 12 weeks and 24 weeks after starting ETI. The primary outcome is orocaecal transit time (OCTT), or the time for food to pass from mouth to caecum. We previously found that OCTT at 24 weeks post ETI (median 360 minutes) did not change significantly vs baseline. In the GIFT-CF3 extension study, we invited participants for repeat MRI scans to evaluate whether the use of ETI lead to a reduction in OCTT after 76 weeks of ETI. Methods: The 21 participants who had completed the GIFT-CF3 study were invited for a repeat MRI scan 76 weeks after starting ETI using the same GIFT-CF3 MRI protocol. The study population were aged between 12–41 years and 13 were F508del homozygous and 8 heterozygous. MRI data collected at 76 weeks included OCTT, small bowel water content, total colonic volume and intestinal motility. Results: In total 11 of the 21 participants returned for repeat MRI scan at 76 weeks. The 11 were aged 13–43 years, 7 were F508del homozygous, 4 heterozygous. For the 11 participants, 8 had a reduction in their OCTT at 76 weeks, 1 had an increase and 2 remained static. The median OCTT after 76 weeks of ETI had reduced when paired to their baseline (ETI76weeks 240 minutes [IQR 180–300] vs baseline >360 minutes [IQR 240->360], Wilcoxon signed rank test p = 0.028). Conclusion: Within the cohort of 11 participants who completed scans at 76 weeks, we observed a reduction in OCTT after the use of ETI for a minimum of 76 weeks (>360 minutes reduced to 240 minutes). An attrition rate of nearly 50% was likely due to the time demands of the study protocol on participants. However, to our knowledge this is the first study to observe a reduction in OCTT while patients were on a modulator therapy.