(232) Increases in Weight-for-Age is Associated with Vegetable Intake in Young Children with Cystic Fibrosis Treated with Lumacaftor/Ivacaftor for 24 Weeks

Background: Modulator therapy has improved nutritional status in individuals with cystic fibrosis (CF), which is associated with favorable outcomes. Due to the increased metabolic demands of CF, nutritional recommendations include energy intake of 110-200% daily estimated needs for healthy individuals. With changes in energy balance after initiation of modulator therapy, these recommendations may no longer be appropriate for some people with CF, and lead to excessive weight gain. Overweight and obesity are being reported and nutrition concerns now include diet quality. Dietary quality in relation to growth among young children starting lumacaftor/ivacaftor therapy has not been examined over a 24-week time period and may provide new data for future nutrition guidance for individuals with CF.

Methods: The purpose of this observational study was to determine the effect of lumacaftor/ivacaftor treatment on growth and diet in children who were medication naïve. Subjects aged 2-5 years with D508/D508 mutations were recruited from the USA and Canada. Length/height, weight and BMI were measured in triplicate and averaged. Z-scores were calculated using the CDC reference data. Dietary data were captured using 3-day weighted food records following study visits. The Healthy Eating Index (HEI) was generated using the USDA scoring system for each recorded day and averaged. Outcomes were assessed before treatment (baseline), 12 weeks and 24 weeks after beginning medication. Mixed longitudinal models were used for analysis over time.

Results: Participants (2.9±1.4 years, mean±SD, 50% female) who completed food records at least their baseline visit plus one other visit (n=14) had significant increases in weight-for-age z-score (WAZ) at 12 weeks (+0.0.6±1.7, p=0.02) and 24 weeks (+0.21±1.8, p=0.001) following therapy. There was no significant change in height-for-age z-score (HAZ), BMI-for-age z-score (BMIZ) or head circumference-for-age z-score (HCZ) at 12 or 24 weeks. Although not statistically significant, percent estimated energy requirement (%EER) decreased at 12 weeks (-7±90%, p=0.54) and 24 weeks (-27±90%, p=0.08). HEI total score did not change over the 24 weeks, however, the total vegetable and greens and beans HEI subgroups both significantly decreased at 24 weeks compared to baseline (-0.73±2.2, p=0.02 and -0.68±2.1, p=0.02, respectively). Pooled visit correlation between total vegetables and WAZ showed a positive association (r=0.35, p=0.04).

Conclusions: WAZ significantly increased over 24 weeks of lumacaftor/ivacaftor therapy and was positively correlated with total vegetable intake. This suggests participants with greater WAZ scores consumed more vegetables. However, over the course of the study total vegetable intake and greens and beans intake decreased and WAZ increased. %EER decreased over the course of the study, but was not statistically significant, likely due to variability in energy intake within this small study sample with some COVID-19 interruptions. In summary children aged 2-5 years with D508/D508 mutations had increased WAZ with no significant changes in HAZ, BMIZ or HCZ and consumed fewer total vegetables and greens and beans following 24 weeks of lumacaftor/ivacaftor therapy.

Acknowledgements: Supported by Vertex Pharmaceutics Incorporated and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR001878.

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