In young children with cystic fibrosis (CF), starting the approved oral treatment Orkambi (ivacaftar/lumacaftar) was associated with favorable changes in nutrition and growth over the first six months of treatment, a small field study has found.
Orkambi, first approved in the United States in 2015 and now indicated for patients as young as 1 year old, was developed to treat CF caused by the F508del mutation. CFTR The gene is the most common disease-causing mutation. Orkambi’s active ingredients, lumacaftor and ivacaftor, called CFTR modulators, are designed to correct defects in the production and function of the CFTR protein caused by the F508del mutation.
Although the treatment has been shown to prevent the buildup of thick, sticky mucus that characterizes CF, little is known about its impact on nutrition and growth, especially in younger patients.
“These data contribute to our understanding of CTFR regulators and their impact on metabolic processes and digestion,” the scientists write.
This new discovery:The effect of lumacaftar/ivacaftar on nutrition and growth in modulator-naive children over 24 weeksPublished in Cystic Fibrosis Journal.
Collecting data on the impact of Orkambi on underlying mechanisms of growth
To date, the use of this treatment has shown some benefit in CF children ages 2 to 5 who have two copies of F508del. A Phase 3 open-label extension study (NCT03125395) found that treatment of this patient population for more than two years with Orkambi improved outcomes, including sweat chloride, pancreatic function, and growth.
However, there is limited real-world data on outcomes related to the underlying mechanisms of nutrition and growth changes in children with CF starting Orkambi.
Normal weight, height, [body mass index] “Health care is crucial early in life, especially during periods of rapid growth,” according to a research team led by scientists at Children’s Hospital of Philadelphia in Pennsylvania.
Therefore, to investigate the effects of Orkambi in more detail, the researchers conducted an observational study (NCT03795363The Orkambi Trial, part of a multicenter study of children from CF centers in the United States and Canada, included 11 children ages 2 to 5.9 years who had not previously received Orkambi.
The research team collected data before treatment and then 12 and 24 weeks after starting Orkambi, including anthropometric measurements, diet, energy expenditure, pancreatic status, and nutritional and inflammatory biomarkers.
Of the 28 children initially enrolled, 18 completed the 12-week follow-up and 21 participated in the 24-week follow-up.
Children ages 2-5 experience age-appropriate weight gain when treated
The results showed that so-called weight-for-age scores increased significantly at both the 12th and 24th weeks.
Weight gain for age “remained within the range typical for growing children, suggesting no transition to overnutrition,” the researchers wrote.
Head circumference-for-age scores also increased significantly by 12 weeks, but not by 24 weeks. Another test measuring body fat showed significant improvement only at 24 weeks.
Laboratory tests showed a decrease in blood carbon dioxide levels and signs of improved lung function at 24 weeks, as well as an increase in creatinine, a waste product of protein digestion. Serum total bile acids, particularly chenodeoxycholic acid and cholic acid, which aid digestion, also increased at 24 weeks. Fecal calprotectin, an indicator of intestinal inflammation, decreased at 12 and 24 weeks.
In summary, [the data] Improved nutrition and growth in young children [Orkambi] Treatment begins after 24 weeks.
In terms of fatty acids, two essential omega-3 fatty acids called alpha-linolenic acid and docosahexaenoic acid decreased significantly between weeks 12 and 24, while mead acid, an omega-9 fatty acid, increased significantly.
“In the present study, although some of these fatty acid changes were statistically significant, all fatty acids remained within the reference range,” the scientists wrote, “hence, these CFTR regulators may be [polyunsaturated fatty acids] And specifically: [essential fatty acids] Condition during the intervention period
Participants had normal mean resting energy expenditure measured in kcal/day before treatment, which did not change significantly after treatment initiation, nor did they change significantly in energy intake (kcal) and percent of estimated energy requirement, which is an estimate of total energy requirement based on age, sex, weight, height, physical activity, and food intake.
Parents reported that adherence to Orkambi ranged from 85% to 100% at mean weeks 4, 16, and 20. CF-specific vitamins ranged from 43% to 100%, and pancreatic enzymes ranged from 71% to 100%.
“In summary, [the data] Improved nutrition and growth in young children [Orkambi] The scientists concluded that “treatment would be terminated after 24 weeks.”
The research was supported in part by an Investigator Initiated Program Award from Vertex Pharmaceuticals, which markets Orkambi, and an award from the Cystic Fibrosis Foundation.
