CF treatment Orkambi shows 2-year benefits in real-world study
Starting CFTR modulator early may yield long-term benefits for children
Starting treatment with the CFTR modulator Orkambi (lumacaftor/ivacaftor) early in life may provide long-term benefits for children with cystic fibrosis (CF), yet lung function improvements may be temporary, according to a real-world study from Hungary.
The study, “Body composition changes and clinical outcomes in pediatric cystic fibrosis during 24 months of lumacaftor ivacaftor therapy based on real-world data,” was published in Scientific Reports.
Vertex Pharmaceuticals’ Orkambi is approved for adults and children as young as 1 who carry F508del, the most common CF-causing mutation, in both copies of their CFTR gene. This mutation results in a faulty CFTR protein that’s rapidly broken down, causing CF lung symptoms and other issues.
Clinical testing showed that Orkambi can improve lung function and reduce chloride levels in sweat, which are abnormally high in CF. It can also improve height, weight, and body fat content in real-life settings. However, less is known about its long-term effects.
The study looked at 49 children with CF with a median age of 9.3, all carrying two copies of F508del, who were followed over two years. They were divided into three age groups (2–5, 6–11, and 12 or older). Four patients, all 12 or older, had developed CF-related diabetes.
CF treatment benefits
Lung function, measured by the percent predicted forced expiratory volume in one second — the amount of air that can be exhaled in one second as a percentage of what’s considered normal for their age, sex, height, and ethnicity — improved temporarily at one year but dropped from a median of 102% at the start to 87% after two years. This decline was greater in children with better lung function at the beginning.
Median chloride levels in sweat dropped significantly, from 75 to 57 millimoles per liter, though this was not associated with lung-function change. There was no link between chloride levels measured at the start and those measured after two years.
Orkambi treatment also improved nutritional status, with patients showing increases in body mass index (BMI), a measure of body fat based on height and weight. However, by the end of the study, more than half of the participants still had measurements lower than the normal average.
CF causes digestive symptoms, in part due to changes in the pancreas, an organ that produces enzymes needed to break down food. The levels of one such enzyme, fecal elastase, a marker of how well the pancreas is working, improved particularly in the 2-to-5-year age group.
The findings suggest that starting Orkambi early in life provides benefits. While lung function increased but then decreased, improvements in sweat chloride, nutritional status, and pancreatic health suggest Orkambi provides long-term benefits for children with CF.
“These findings underscore the potential benefits of early initiation of CFTR modulator therapy in pediatric CF patients, particularly in improving nutritional status and pancreatic function,” the researchers wrote.
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