Nutritional impact of CFTR modulators in children with cystic fibrosis

Abstract

BackgroundNutritional status is a major prognostic factor for breathing and the survival of patients with cystic fibrosis (CF). Since 2012, the development of CFTR modulators has considerably transformed the outcome of this disease. Indeed, both lung function and body mass index are improved by CFTR modulators, such as Lumacaftor/Ivacaftor. However, few data exist regarding the outcome of nutritional intakes under Lumacaftor/Ivacaftor.MethodsWe conducted a prospective single-center study in children with CF treated with Lumacaftor/Ivacaftor to evaluate their nutritional intake before and after treatmentResultsThirty-four children were included in this study, with a median age of 12.4 years [11.9; 14.7]. There was no significant improvement in weight, height or BMI. Patients' total energy intake was not significantly changed with Lumacaftor/Ivacaftor, while carbohydrate intakes decreased significantly. We found that blood levels of vitamin E and Selenium were significantly increased under Lumacaftor/Ivacaftor, without a significant increase in supplementation. In patients with a BMI Z-score < 0 at treatment initiation, there was a significant improvement in weight and BMI Z-score, while TEI and carbohydrate intakes were significantly lower.ConclusionWe showed that treatment with Lumacaftor/Ivacaftor improved the nutritional status of patients without necessarily being associated with an increase in nutritional intake. Although these data need to be confirmed in larger cohorts, they support the hypothesis that weight gain under modulators is multifactorial, and may be related to a decrease in energy expenditure or an improvement in absorption.

Impact of elexacaftor/tezacaftor/ivacaftor on lipid and fat‐soluble vitamin levels and association with body mass index

“…An increase in BMI in both children and adults has been noted in many studies after the initiation of modulator therapies, with greater weight gain after highly effective modulator therapies such as Iva (for PwCF with gating mutations) and ETI 21,22,28‐36 . Petersen and colleagues found that the mean rate of change in BMI was 1.47 kg/m 2 /yr (95% confidence interval, 1.08–1.87) greater after initiation of ETI.…”

Changes in vitamins and trace elements after initiation of highly effective CFTR modulator therapy in children and adults with cystic fibrosis – a real-life insight

“…Other reasons might include changes in intestinal pH, intestinal absorption of bile salts or changes in intestinal transit time [ 46 ]. Gaschignard et al reported significantly increased Vitamin E levels 10 months after therapy with luma-/ivacaftor and Gelzo et al reported higher vitamin E levels after luma-/ivacaftor therapy as well [ 21 , 30 ]. Sommerburg et al on the contrary reported a moderate but significant decrease in vitamin E and vitamin E/cholesterol one and two years after luma-/ivacaftor [ 22 ].…”

“…Sommerburg et al on the contrary reported a moderate but significant decrease in vitamin E and vitamin E/cholesterol one and two years after luma-/ivacaftor [ 22 ]. Vitamin A and D levels also rose, not-significantly in one study [ 30 ] but another report shows increased vitamin A levels [ 22 ]. Similar results have been published for ETI therapy: Both vitamins A and D levels increased in an adult cohort and vitamin A increased in a pediatric cohort [ 28 , 41 , 42 ].…”

“…There is no clear link between optimal vitamin E levels and health in CF [ 29 ]. Higher levels of Vitamin E have been shown after therapy with luma-/ivacaftor [ 21 , 30 ] and with ETI treatment [ 23 ].…”

“…Selenium is also a trace element with antioxidative, anti-inflammatory and metabolic functions. An increase in selenium levels was noticed after 10 months of treatment with lumacaftor/Ivacaftor [ 30 ]. It is unclear though if an optimal selenium level exists and supplementation of selenium is not associated with better patient outcomes in CF [ 8 ].…”