(198) Weight and Body Composition in School-Age Children with CF and Extended Modulator Therapy

Background: Body mass index (BMI) greater than the 50^th percentile has long been the nutritional target for children with cystic fibrosis (CF). Increasing numbers of children have become overweight or obese. [1] While previous studies have correlated higher BMI with higher lung function, newer research highlights that lung function and health is advantaged by lean body mass. [2] A high percent body fat and low skeletal muscle mass is common among individuals with CF across all BMI levels, and suggests that BMI is a suboptimal marker of nutritional status. [3] To date, the effect of modulators on body composition in children with CF has not been comprehensively documented. Based on previous studies, largely in adolescents and adults, we hypothesize that children with CF on modulator therapy will experience a sustained increase in fat mass. The effect of extended modulator therapy on skeletal muscle mass remains unknown.

Methods: This abstract uses baseline data from a study with a longitudinal, observational design to assess the BMI and body composition of children ages 6-11 years old with CF who were poised to initiate elexacaftor/tezacaftor/ivacaftor (Trikafta) therapy and who 1) had (n=27) or 2) had not (n=10) been treated with modulator therapy. Modulator treatment and BMI data were extracted from the medical record and body composition was assessed via bioelectrical impedance analysis (BIA) using InBody 770 equipment.

Results: Significant differences were noted at baseline assessment between those who were on modulator prior to enrollment versus those naïve to modulator therapy. Children in the previous modulator treatment group had been on therapy for an average of 3.7 years, with a range of 1.9 to 4.5 years. Those naïve to modulator were younger on average at study enrollment (8.4 years vs 9.7 years, p=0.05). Children previously on modulators were noted to have higher BMI (mean BMI percentile 73% vs 54%, p=0.07), fat mass index (5.03 vs 3.15, p=0.01), and percent body fat (25.5% vs 16.9%, p=0.007) as compared to those naïve to modulators. Lean body mass index (13.88 vs 13.73, p=0.45) and skeletal muscle mass index (7.11 vs 6.91, p=0.31) were comparable.

Conclusions: Our study baseline data offered a novel opportunity to identify modulator effects over several years on body weight and composition for children with CF. Data suggest that extended modulator therapy is associated with a persisting increase of body weight and fat mass, but not skeletal muscle mass, of prepubescent children. These data suggest a need for nutritional and physical activity interventions to optimize overall improvement with modulator therapy. The further effect of elexacaftor/tezacaftor/ivacaftor therapy on weight, body composition and muscle strength is being evaluated.

Acknowledgements: This work was supported by Vertex Pharmaceuticals [CTA0001313, 2022].

References: 1. Kutney KA, Sandouk Z, Desimone M, Moheet A. Obesity in cystic fibrosis. Journal of clinical & translational endocrinology. 2021;26:100276.

2. Calella P, Valerio G, Brodlie M, Donini LM, Siervo M. Cystic fibrosis, body composition, and health outcomes: a systematic review. Nutrition. 2018;55-56:131-9.

3. King SJ, Nyulasi IB, Strauss BJ, Kotsimbos T, Bailey M, Wilson JW. Fat-free mass depletion in cystic fibrosis: associated with lung disease severity but poorly detected by body mass index. Nutrition. 2010;26(7-8):753-9.