A systematic review of the impact of Elexacaftor/Tezacaftor/Ivacaftor on body composition in people with cystic fibrosis.

Elexacaftor/Tezacaftor/Ivacaftor (ETI) has led to improved lung function, life expectancy, and body mass index for people with Cystic Fibrosis (CF). The aim of this systematic review was to evaluate the impact that ETI has had on body composition in people with CF. A systematic review was performed using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials. Quality assessment using the Joanna Briggs Institute critical appraisal tools were performed. Results were summarised narratively. Five observational cohort studies involving a total of 185 participants were reviewed. Three studies showed an increase in fat mass (7.0-8.6 kg, 13.2-14.3 kg, and 13.4-15.5 kg). Two studies reported an increase in fat-free mass (49.4-50.1 kg, 52.5-55 kg), while one reported a decrease (50.5-48.9 kg). Two studies found an increase in fat mass index (4.1-6.3 kgm/ and 4.7-5.4 kg/m) and fat-free mass index (17.4-17.7 kg/m and 18.1-18.8 kg/m). Two studies observed an increase in percentage body fat mass (12.1-15.4% and 23.1-27.6%). Four studies were classified as low quality, while one was considered medium quality. This review suggest that commencing ETI results in changes in body composition. Firm conclusions about the type and distribution of change in body composition cannot be made due to limited studies, high heterogeneity, and methodical weaknesses. It highlights the necessity for higher quality and longer-term studies to explore the impact that ETI is having on body composition.