# Impact of Elexacaftor-Tezacaftor-Ivacaftor on Gastrointestinal Symptoms, Intestinal Ultrasound, and Pancreatic Stiffness in Cystic Fibrosis

## TL;DR

A new drug combination improves gut health, pancreatic stiffness, and blood sugar control in cystic fibrosis patients.

## Contribution

The study shows that ETI treatment significantly reduces gastrointestinal symptoms and improves pancreatic and metabolic health in cystic fibrosis.

## Key findings

- ETI treatment reduced abdominal pain and IUS abnormalities in cystic fibrosis patients.
- Pancreatic stiffness normalized after one year of ETI therapy.
- ETI improved glycemic control and increased high-density lipoproteins cholesterol.

## Abstract

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. The aim of this prospective study was to explore ETI's effects on the gastrointestinal manifestations of cystic fibrosis.

In this prospective cross-sectional study, performed in a single tertiary referral center for cystic fibrosis, 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.

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 and recurrent diarrhea from 77% to 9% (P < 0.0001). Pancreatic stiffness normalized after 1-year treatment (T0: 4.21 vs T12: 5.7 kPa, P < 0.05). Body mass index 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). High-density lipoproteins cholesterol increased, whereas low density lipoprotein and triglycerides remained stable.

ETI normalized IUS parameters and significantly improved pancreatic stiffness, gastrointestinal symptoms, glycemic control, and cholesterol metabolism in pwCF.