Treatment with CFTR Modulators for Cystic Fibrosis: What a Pediatric Gastroenterologist Needs to Know

Abstract

Highlights: What are the main findings? mCFTRs, particularly ETI therapy, significantly improve gastrointestinal function and nutritional status and reduce intestinal inflammation in pediatric patients with cystic fibrosis. These improvements are accompanied by enhanced levels of fat-soluble vitamins and changes in body composition. By restoring CFTR protein function, modulator therapy may positively influence bone density and structure through both direct effects on bone cells and indirect mechanisms related to improved overall health. Pediatric gastroenterologists must incorporate modulator-driven changes into routine clinical monitoring, with special attention to nutrition, bone density, and hepatobiliary markers. These findings support a shift toward personalized, multidisciplinary care strategies that reflect the expanded systemic benefits and emerging risks of mCFTRs in children. Background: Cystic fibrosis (CF) is a multisystemic disorder caused by CFTR gene mutations, leading to impaired protein function and affecting pulmonary, gastrointestinal, hepatobiliary, skeletal, and nutritional health. The advent of CFTR modulators—especially the triple therapy elexacaftor/tezacaftor/ivacaftor (ETI)—has revolutionized clinical management, offering genotype-specific benefits beyond pulmonary outcomes. Pediatric gastroenterologists must now recognize and address emerging gastrointestinal and nutritional challenges introduced by modulator therapy. Methods: A narrative review was conducted to assess the impact of CFTR modulators on gastrointestinal function, nutritional status, bone health, and hepatobiliary involvement in pediatric patients. A structured literature search was performed using PubMed, EMBASE, and Scopus databases. Filters included articles in English or Spanish. Following full-text review based on relevance and quality, 68 articles were selected for inclusion in this review. Results: CFTR modulators have demonstrated potential improvements in gastrointestinal function, nutrient absorption, weight gain, and bone mineral density. In pediatric populations, ETI therapy has been associated with early increases in lean mass, enhanced vitamin levels, and promising trends in bone microarchitecture. However, variable outcomes regarding liver function and bone mineral density highlight the need for careful monitoring. Conclusions: While CFTR modulators present novel opportunities for systemic improvement in CF, their long-term impact on digestive and skeletal health in children remains under investigation. Pediatric gastroenterologists play a pivotal role in monitoring nutritional and hepatobiliary outcomes, optimizing treatment plans, and guiding personalized care strategies in the era of CFTR modulation.