ABSTRACT
Background: Modulator therapy has improved nutritional status in individuals with cystic fibrosis (CF), which is associated with favorable outcomes. Because of the high metabolic demands of CF, nutritional recommendations include energy intake of 110% to 200% of 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 CFand may lead to excessiveweight gain. Overweight and obesity are being reported, and nutrition concerns now include dietary quality. Dietary quality in relation to growth in young children starting lumacaftor/ivacaftor therapy has not been examined over a 24-week period and may provide new data for future nutrition guidance for individuals with CF. Method(s): The purpose of this observational study was to determine the effect of lumacaftor/ivacaftor treatment on growth and diet in medicationnaive children. Subjects aged 2 to 5 with D508/D508 mutations were recruited from the United States and Canada. Length/height, weight, and body mass index (BMI) were measured in triplicate and averaged. Z-scores were calculated using Centers for Disease Control and Prevention reference data. Dietary data were captured using 3-day weighted food records after study visits. The Healthy Eating Index (HEI) was generated using the U.S. Department of Agriculture scoring system for each recorded day and averaged. Outcomes were assessed before treatment (baseline) and 12 and 24 weeks after beginning medication. Mixed longitudinal models were used for analysis over time. Result(s): Participants (mean age 2.9 +/- 1.4, 50% female) who completed food records for at least their baseline visit plus one other visit (n = 14) had significant increases inweight-for-age z-score (WAZ) 12 (0.6 +/- 1.7, p = 0.02) and 24 (0.21 +/- 1.8, p = 0.001) weeks after therapy. There was no significant change in height-for-age (HAZ), BMI-for-age (BMIZ), or head circumference- for-age (HCZ) z-score at 12 or 24 weeks. Although not statistically significant, percentage estimated energy requirement (%EER) decreased at 12 (-7 +/- 90%, p = 0.54) and 24 (-27 +/- 90%, p = 0.08) weeks. HEI total score did not change over the 24 weeks, although vegetables and greens and beans HEI subgroup scores decreased significantly from baseline to 24 weeks (-0.73 +/- 2.2, p = 0.02;-0.68 +/- 2.1, p = 0.02, respectively). Pooled visit correlation between total vegetables and WAZ indicated a positive association (r = 0.35, p = 0.04). Conclusion(s): WAZ increased significantly over 24 weeks of lumacaftor/ ivacaftor therapy and was positively correlated with total vegetable intake, suggesting that participants with greater WAZ scores consumed more vegetables, although over the course of the study, total vegetable intake and intake of greens and beans decreased, and WAZ increased. %EER decreased over the course of the study, but not statistically significantly so, probably because of variability in energy intake within this small study sample with some COVID-19 interruptions. In summary, WAZ of children aged 2 to 5 with D508/D508 mutations increased, with no significant changes in HAZ, BMIZ, or HCZ, and they consumed fewer total vegetables and greens and beans after 24 weeks of lumacaftor/ivacaftor therapy. Acknowledgements: Supported by Vertex Pharmaceutics Inc. and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR001878.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
ABSTRACT
Background: With the introduction of new cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (elexacaftor/tezacaftor/ ivacaftor), peoplewith CF experiencing severe lung disease can experience significant improvements in clinical symptoms. Method(s): This single-center institutional review board-approved retrospective chart review identified patients with advanced lung disease who met criteria for a compassionate use or expanded access program because of high risk of death or transplant need within 2 years. Clinical data collection for all patients began at baseline, 2 to 4 weeks after therapy initiation, and continued every 3 months for 2 years. Datawere collected on demographic characteristics, clinic progress notes, clinical labs, forced expiratory volume in 1 minute (FEV1),weight, body mass index, respiratory colonization, and hospitalizations after drug initiation. Patients also completed sinus and chest computed tomography (CT) to track clinical changes. Result(s): Eighteen people with CF (aged 15-49, 56% male) from a large midwestern CF center who initiated drug therapy between July and September 2019 in an inpatient hospital or clinic setting were identified. Clinical markers (Table 1) indicated that modulator therapy was well tolerated and not discontinued by any participant;safety lab values did not indicate medical concern or discontinuation. There were 90 admissions for the group in the 2 years before therapy and 17 admissions during the 2 years after, although seven of the posttherapy admissions were for nonrespiratory indications. Monitoring results indicated the safety of modulator therapy because there were no adverse clinical occurrences or laboratory events, and all patients presented with universal stabilization. There have been no deaths and no transplants. Unlike lumacaftor/ivacaftor, therewere no problems with chest tightness or any difficulty with troublesome increases in expectoration burden or choking during initiation of therapy. Most had significant reduction in or loss of spontaneous cough and sputum production. The impact on microbial colonization is unclear, because even in this severe group, inability to produce sputum on command led to considerable missing data in follow-up, leaving colonization status at follow-up unclear. Conclusion(s): This study focused on people with CF who qualified for modulator therapy based on advanced lung disease. Initiation of modulator therapy was deemed safe and resulted in objective positive changes in nutrition;cough;FEV1);and subjective reports of clinical status, level of activity, and reduction in burden of treatment. No evidence was found of difficulty managing the increased expectoration during initial therapy. Limitations were noted in missing data during the COVID-19 pandemic, small sample size, and delayed follow-up for drug monitoring.(Table Presented) Clinical indicators before and after modulator therapy *Completed post-drug initiation (earlier than 12 months), **24 months before and after therapy initiationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved
ABSTRACT
From September 2020 until January 2022, children with CF in the UK aged 6–12 years homozygous for F508del had a choice of CFTR modulators: Lumacaftor/ivacaftor(LUM/IVA) or tezacaftor/ivacaftor (TEZ/IVA)+ ivacaftor (IVA). Although benefit of the individual agents has been demonstrated in clinical trials, there is no direct comparison between treatments.1 Objectives: Review of Forced Expiratory Volume in 1 second (FEV1) and nutritional clinical benefits of switching from LUM/IVA to TEZ/IVA + IVA. Method: A retrospective review of 18 paediatric patients (pts) swapped from LUM/IVA to TEZ/IVA + IVA. Data collected of length of time on each CFTR modulator, body mass index (BMI) centile, FEV1 (% predicted and zscore). FEV1 data analysed using ANOVA test. Results: 12 female;6 male pts (Mean age 9 yrs 6mths (range 8–12 years)). Two pts swapped from LUM/IVA due to tolerability issues. The other families chose to swap. Mean length of time was 13 mths (±1.3) on LUM/IVA and 9mths ± 1.2 on TEZ/IVA + IVA. Spirometry;table 1 (Table Presented) Conclusion: Swapping CFTR modulators for most pts offered no clear improvement in FEV1 or BMI, the surrogate markers of lung and nutritional health. However, pts did not experience the usual decline in FEV1 seen in CF. There are many potential confounding factors that need to be considered, including that data was collected during the COVID pandemic. As new modulators are developed, further research will be required to better understand their mechanism of action in individual pts to guide optimal personalised prescribing. 1 Walker S., et al., A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11years with cystic fibrosis, J CYST FIBROS;June 2019;18(708–713).