Body mass, linear growth, and body composition before and after the introduction of elexacaftor/tezacaftor/ivacaftor among children and adults with cystic fibrosis

BACKGROUND & AIMS: Weight gain after elexacaftor/tezacaftor/ivacaftor (ETI) initiation among people with cystic fibrosis (CF) has been widely reported. How these weight changes compare with pre-existing trends, how they compare with linear growth, if they persist over time, and how they affect body composition have yet to be investigated. We assessed changes in body mass, linear growth, and body composition after ETI initiation.

METHODS: Anthropometric data from people with CF in the Danish CF Registry were collected from 5 years pre-ETI initiation to 2 years post. Linear mixed-effects models with linear splines were used to assess changes in body mass index (BMI) in adults, and in BMI-for-age z-score (BMZ) and height-for-age z-score (HAZ) in children. Fat and fat-free mass from dual-energy X-ray absorptiometry (DXA) were compared using paired t-tests in adults.

RESULTS: We included 392 people with CF. Among 154 children, BMZ was stable 5 years pre-ETI. Mean (95%CI) BMZ increased from -0.22 (-0.37, -0.07) at ETI initiation to 0.24 (0.05, 0.43) 2 years later. BMZ increased at a continuously higher rate post-ETI initiation compared to pre-ETI. HAZ increased by 0.05 (0.01, 0.09) per year pre-ETI, then remained stable post-ETI initiation, with no change from ETI initiation (0.12 (-0.03, 0.26)) to 2 years post-ETI. Among 238 adults, BMI increased by 0.05 (0.004, 0.10) kg/m2 per year pre-ETI. BMI increased from 22.55 (22.08, 23.02) kg/m2 at ETI initiation to 23.75 (23.25, 24.25) kg/m2 after 2 years, but the annual rate of change returned to pre-ETI trends after 9 months. In a subset of 115 adults with available DXA data, mean fat mass index increased by 0.68 kg/m2 (0.01, 1.35) 1 year post-ETI initiation, with no significant gain of fat-free mass index.

CONCLUSIONS: Children with CF continued to increase their BMZ 2 years post-ETI initiation, while HAZ remined stable. The rate of change in BMI returned to pre-ETI trends among adults with CF. Adult BMI gains were primarily driven by an increase of fat mass.