Orkambi over 2 years helps clear trapped air in children ages 6-11
Treatment didn’t prevent abnormal widening of the airways, stop lung damage
Taking Orkambi (lumacaftor/ivacaftor) for more than two years helped clear trapped air from the lungs of children with cystic fibrosis (CF), ages 6-11, but didn’t prevent an abnormal widening of the airways, a real-world study finds.
The findings indicate the medication may not completely stop lung damage from progressing and underscore the “importance of collecting [real-world] imaging data and the ongoing development and testing of more effective CFTR modulators,” the researchers wrote in “The clinical impact of Lumacaftor-Ivacaftor on structural lung disease and lung function in children aged 6–11 with cystic fibrosis in a real-world setting,” which was published in Respiratory Research.
A feature of CF is abnormally thick mucus that builds up in organs. In the lungs, the mucus clogs the airways and makes it difficult to breathe and clear out infections. The airways can become damaged and widen, a condition known as bronchiectasis.
The disease is caused by mutations in the gene that codes for CFTR, a protein that acts like a gate or channel on the cell surface, helping to regulate the flow of chloride ions and water in and out, and control mucus thickness.
The most common mutation, F508del, results in an improperly folded protein being produced, which is broken down by the cell’s quality control mechanisms before it reaches the cell surface.
Orkambi in a real-world setting
Orkambi combines lumacaftor, which helps the faulty protein fold correctly and reach the cell surface, and ivacaftor, which holds the channel open. This helps ease the symptoms of CF.
Marketed by Vertex Pharmaceuticals and available as oral tablets or granules, it can be used in patients ages 1 and older who have the F508del mutation in both copies of the CFTR gene.
A team led by researchers in Ireland focused on children ages 6-11 and how well they responded to Orkambi in a real-world clinical setting for more than two years.
The study included 71 children (36 girls, 25 boys) with a mean age of 8.7 years. Most (96.3%) were adhering to treatment, based on the number of prescriptions picked up from the pharmacy.
Of the 71 children, 31 (43.7%) had CT scans at three time points — at the beginning of the study (baseline), after one year, and after two years.
The researchers used software called PRAGMA-CF to calculate a percent disease score that reflects areas of the lung with evidence of damage along with a percent of trapped air and a percent score of the areas affected by bronchiectasis.
There was no significant change in mean percent disease from baseline to two years with Orkambi (2.78 vs. 2.25).
Mean percent trapped air decreased significantly over two years from 13.88 to 7.09, indicating the medication helped clear air from the lungs. Mean percent bronchiectasis significantly increased from 0.82 to 1.24, however, suggesting it worsened despite treatment.
In clinical testing, Orkambi resulted in a decrease in the lung clearance index, indicating improved lung ventilation. In this study, there was no significant change, however, “likely due to the small number of measurements,” the researchers wrote.
A feature of bronchiectasis is the abnormal ratio between the dimensions of the air passages and the diameter of the blood vessels that supply the lungs.
In healthy lungs, this ratio remains unchanged. However, in bronchiectasis, it tends to increase progressively while moving deeper into the airway “tree,” from larger to smaller air passages.
When measured based on the inner diameter of the air passages, the ratio increased significantly over four generations of “branches” over two years, indicating changes to structure.
While there were no changes in ppFEV1, a measure of the maximum amount of air breathed out in one second, the number of yearly hospitalizations due to exacerbations decreased from an average of 1.18 to 0.87. That difference was not statistically significant.
Significant improvements were seen in weight, height, and body mass index (BMI), a measure of body fat. These were “similar to those reported in clinical trials and real world studies,” the researchers wrote.
Trikafta (elexacaftor/tezacaftor/ivacaftor), a more recent CFTR modulator also marketed by Vertex, is preferred for patients with the F508del mutation. The findings here remain relevant because Orkambi “is still in use in younger children and may remain in use in jurisdictions where approval or funding is not in place for other modulators,” the researchers wrote.
The lack of a control group that precluded establishing the precise effect of Orkambi on structural lung disease was mentioned as a limitation of the study.
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