Impact of Elexacaftor-Tezacaftor-Ivacaftor on gastrointestinal symptoms, intestinal ultrasound and pancreatic stiffness in cystic fibrosis

BACKGROUND AND AIMS: – Elexacaftor-Tezacaftor-Ivacaftor (ETI) is a highly effective therapy for over 70% of people with cystic fibrosis (pwCF), improving lung disease, quality of life, and survival. This prospective study aimed to explore ETI's effects on the gastrointestinal (GI) manifestations of CF.METHODS: – In this prospective cross-sectional study, performed in a single tertiary referral center for CF, clinical and laboratory data, intestinal ultrasound (IUS) findings, and pancreatic stiffness (2D-SWE) were assessed at baseline (T0) and during ETI treatment at 6 and 12 months (T6, T12). Abdominal pain, alterations in stool frequency, form, and consistency (diarrhea, constipation) were monitored.RESULTS: – The participants were 86 pwCF (57% male, mean age 21.6 years), and 22 healthy controls enrolled for pancreatic stiffness comparison. IUS abnormalities (e.g., bowel wall thickening, inspissated intestinal contents, lymph node hypertrophy) and abdominal pain (63% at T0 to 2% at T12) significantly decreased (p<0.05). Constipation dropped from 7% at T0 to 0% at T12, recurrent diarrhea from 77% to 9% (p<0.0001). Pancreatic stiffness normalized after one-year treatment (T0: 4.21 vs. T12: 5.7 kPa, p<0.05). BMI increased (T0: 21.0 vs. T12: 22.4 kg/m2, p<0.001), and glycemic control improved, with reduced fasting glucose (T0: 97.8 vs. T12: 86 mg/dL, p<0.001) and hemoglobin A1c (38 vs 36 mmol/mol, p<0.001). HDL cholesterol increased, while LDL and triglycerides remained stable.CONCLUSIONS: – ETI normalized IUS parameters and significantly improved pancreatic stiffness, GI symptoms glycemic control, and cholesterol metabolism in pwCF.