Dietary intake remains unchanged while nutritional status improves in children and adults with cystic fibrosis on Elexacaftor/Tezacaftor/Ivacaftor

Abstract

Background: Cystic fibrosis (CF) is a genetic disorder involving multi-organ dysfunction, with nutritional status playing a crucial role in disease progression. Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulator therapy, particularly the combination Elexacaftor/Tezacaftor/Ivacaftor (ETI), has shown numerous clinical benefits, including significant improvements in nutritional status. However, the factors driving this nutritional improvement, especially the potential role of increased dietary intake, remain underexplored. This study aimed to assess changes in nutritional status and dietary intake in patients with CF (pwCF) treated with ETI.

Methods: 62 pwCF (36 children, 26 adults) were analyzed in a prospective, realworld, multicenter study (https://clinicaltrials.gov/study/NCT06072365). Dietary intakes were assessed via 3-day food diaries collected at baseline (M0) and one year after ETI treatment initiation (M12).

Results: Over the first year of ETI treatment, Body Mass Index (BMI) significantly increased with a median BMI Z-score gain of 0.2 (IQR: 0.7) for children and median BMI gain of 1.0 kg/m² (IQR: 1.8) for adults. Notably, these gains occurred without a significant increase in median daily caloric intake (2216 kcal (IQR: 750) at M0 vs. 2266 (IQR: 733) kcal at M12). Pancreatic enzyme requirements and calprotectin decreased significantly with ETI (p < 0.001 and p < 0.01, respectively), indicating improved pancreatic function and intestinal inflammation in some patients. Seven patients became overweight after one year of ETI.

Conclusion: ETI therapy enhances nutritional status in pwCF, independently of increased caloric intake. Further research is essential to refine dietary recommendations under ETI treatment, aiming to prevent overweight and obesity while optimizing health outcomes.

Keywords: Adults; CFTR modulator; Children; Cystic fibrosis; Dietary intake; Nutrition.