Impact of highly effective modulator therapy on gastrointestinal symptoms and features in people with cystic fibrosis

Martina Cecchetti; Luca Scarallo; Paolo Lionetti; Chee Y Ooi; Vito Terlizzi

doi:10.1016/j.prrv.2024.07.004

Impact of highly effective modulator therapy on gastrointestinal symptoms and features in people with cystic fibrosis

Paediatr Respir Rev. 2024 Sep 20:S1526-0542(24)00076-9. doi: 10.1016/j.prrv.2024.07.004. Online ahead of print.

Authors

Martina Cecchetti¹, Luca Scarallo², Paolo Lionetti², Chee Y Ooi³, Vito Terlizzi⁴

Affiliations

¹ Department of Health Sciences, University of Florence, Florence, Italy; Meyer Children Hospital IRCCS, Florence, Italy.
² Gastroenterology and Nutrition Unit, Meyer Children's Hospital IRCCS, Florence, Italy; Department of NEUROFARBA, University of Florence, Florence, Italy.
³ School of Clinical Medicine, Discipline of Paediatrics & Child Health, UNSW Medicine & Health, University of New South Wales, Sydney, Australia; Department of Gastroenterology, Sydney Children's Hospital Randwick, NSW, Australia.
⁴ Meyer Children's Hospital, IRCCS, Department of Paediatric Medicine, Cystic Fibrosis Regional Reference Center, Meyer Children's Hospital, Florence, Italy. Electronic address: vito.terlizzi@meyer.it.

PMID: 39341749
DOI: 10.1016/j.prrv.2024.07.004

Abstract

Highly effective modulator therapy (HEMT), particularly the triple combination elexacaftor-tezacaftor-ivacaftor (ETI), significantly improved clinical outcomes and quality of life in people with Cystic Fibrosis (pwCF). This review analyzes current knowledge on the impact of HEMTs on gastrointestinal (GI) symptoms and features in pwCF. A descriptive review of English literature until February 29, 2024, was conducted using medical databases. Observational studies and clinical trials addressing GI reflux disease (GERD), lower GI symptoms and pancreatic disease were considered. Studies report positive effects of HEMTs on pH levels and bicarbonate secretion as well as improvement on intestinal inflammation. HEMTs also demonstrated positive effects on GERD and lower GI symptoms or conditions CF related such as dysbiosis. Taking ETI during pregnancy could also allow resolution of meconium ileus in fetuses with CF. The best benefits were observed in pancreatic function, potentially delaying CF-related diabetes and recovering pancreatic function in some children on ETI. Larger trials, particularly in pediatric populations, need to confirm these findings and explore long-term effects.

Keywords: Children; ETI; Elexacaftor; GERD; Ivacaftor; Lumacaftor; Meconium ileus; Pancreatitis; SIBO; Tezacaftor.

Publication types

Review