Effect of elexacaftor-tezacaftor-ivacaftor on body weight and metabolic parameters in adults with cystic fibrosis

• Published in: Journal of cystic fibrosis 2022-03, Vol.21 (2), p.265-271
• Main Authors: Petersen, Max C., Begnel, Lauren, Wallendorf, Michael, Litvin, Marina
• Format: Article
• Language: English
• Subjects: Adult; Aminophenols - adverse effects; Benzodioxoles - adverse effects; BMI; Body weight; Body Weight - drug effects; Cardiometabolic Risk Factors; CFRD; Chloride Channel Agonists - adverse effects; Cholesterol; Cystic Fibrosis - drug therapy; Elexacaftor-tezacaftor-ivacaftor; Humans; Indoles - adverse effects; Metabolism; Obesity; Pyrazoles - adverse effects; Pyridines - adverse effects; Pyrrolidines - adverse effects; Quinolones - adverse effects; Retrospective Studies
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2021.11.012

•Elexacaftor-tezacaftor-ivacaftor (ETI) treatment is associated with increased BMI.•ETI treatment is associated with increased blood pressure.•ETI is associated with changes in glycemic and plasma lipid profiles.•The effect of ETI on BMI was not affected by CFTR genotype or CFRD status. Though weight gain has been reported in some clinical trials of CFTR modulators, the effect of elexacaftor-tezacaftor-ivacaftor on body weight, body mass index (BMI), blood pressure, lipids and glycemic control in the real-world setting remains incompletely described. We performed a single-center, retrospective, observational analysis of the effect of elexacaftor-tezacaftor-ivacaftor on body weight and cardiometabolic parameters in 134 adult CF patients of the Washington University Adult Cystic Fibrosis Center. Body weight, BMI, and blood pressure were extracted from outpatient clinic visits for the year preceding and the period following the initiation of elexacaftor-tezacaftor-ivacaftor. Other metabolic parameters were extracted at baseline and at latest available follow-up. A mean of 12.2 months of follow-up data was available for analysis. The mean rate of change in BMI was 1.47 kg/m2/yr (95% CI, 1.08 to 1.87) greater after initiation of elexacaftor-tezacaftor-ivacaftor. Significant increases in blood pressure were observed. In those without CFRD, random blood glucose and hemoglobin A1c were decreased after elexacaftor-tezacaftor-ivacaftor initiation. In those with CFRD, elexacaftor-tezacaftor-ivacaftor increased serum total cholesterol, HDL-cholesterol, and LDL-cholesterol. In this single-center, retrospective, observational study of 134 adults with CF, initiation of elexacaftor-tezacaftor-ivacaftor was associated with increases in BMI at a mean follow up of 12.2 months. Changes in other cardiometabolic risk factors were also observed. Widespread use of elexacaftor-tezacaftor-ivacaftor may be expected to increase the incidence of overnutrition in the CF population.