Highly effective CFTR modulator therapy affects body composition in people with cystic fibrosis

ABSTRACT

Introduction: Elexacaftor-tezacaftor-ivacaftor was approved for cystic fibrosis (CF) patients ≥12 years old in October 2019. Clinical studies have shown impressive weight gain in patients on this triple combination therapy (TCT). There are no body composition goals set for CF patients as these standards have not yet been validated in the CF population and there are no data showing the effects of TCT on body composition. There are limitations of BMI, such as the lack of knowledge of the patient's body fat percentage (BF%) and skeletal muscle mass (SMM). We aim to improve our knowledge of TCT effects on CF patient's body composition over time so we may provide more effective nutritional and physical activity recommendations with a goal towards health weight gain. Method: The clinic offers InBody Bioelectrical Impedance Analysis scans. The care team then evaluates the patient, reviews results and offers dietary and exercise recommendations. Our patients were instructed to continue their previous nutritional recommendations, exercise regimens, and daily activities after starting TCT. Eligible patients received a pre- and post-InBody assessment using the following criteria they must have had InBody test prior to starting TCT and be in the clinic for post-testing within 3 months of starting TCT. We measured weight, BMI, skeletal muscle mass, and body fat percentage (BF%) before starting TCT and at post-testing. Results: The adult center has 143 patients. Of these, 38 completed baseline InBody testing, exercise and nutrition assessment prior to starting TCT. Eighteen out of the 38 patients (47%) completed the study with a post-TCT assessment. Study patients showed significant weight gain with mean weight increasing from 144 to 151 pounds. Mean BMI increased from 23 to 24. There was an improvement in SMM (60.23 to 61.7 lb), with minimal change in BF% (24.6% to 24.8%). After starting TCT, 11/18 (61%) reported increased appetite, prolonged stamina during exercise, and increased appetite after exercise. Conclusion: In this study there was a notable increase in SMM with minimal change in BF%. SMM increases are more desirable due to skeletal tissue's roles in the body as it contributes to mobility, stability, posture, circulation, and digestion. TCT promoted weight gain and improvements in SMM with minimal change in BF%. Given this preliminary data it is unknown if these changes in body composition are directly related to TCT or an effect of the improved energy levels and exercise tolerance, that were seen in the majority of our patients. Larger studies are needed to further evaluate these results. As CF patients live longer it is imperative that healthcare providers prepare them for healthy aging. Part of this is encouraging proper exercise and the intake of a healthy diet. The COVID-19 pandemic impacted our study by decreasing our sample size dramatically, hence it is not statistically significant. Post-assessments were halted due to cancellations of in-clinic visits. Our clinic will continue to measure baseline- and post-assessments, focusing on sustainable clinic flow operations, increasing education, and increasing sample size through collaboration with the pediatric CF center.