Trikafta seen to improve airways structures in CF in real world study
Treatment for 6 months found to reduce mucus plugging in lungs
Trikafta treatment for six months in people with cystic fibrosis (CF) was found in a real-world study to reduce the thickness of the airway walls and lead to less excessive mucus plugging in the lungs.
Overall, as observed by MRI, the approved CF therapy improved structural abnormalities in the lungs, alongside gains in lung function and nutritional status.
According to researchers, these findings also show that noninvasive MRI scans are a safe and sensitive method to monitor changes in the structure of the airways in response to treatment over time.
“Importantly, MRI can assess disease progression and short-term response to therapies suggesting that this imaging technique could represent an outcome for clinical trials and for testing novel therapeutics,” the team wrote.
The MRI study, “Structural changes in lung morphology detected by MRI after modulating therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with cystic fibrosis,” was published in the journal Respiratory Medicine.
Investigating Trikafta’s effect on mucus plugging, airway wall thickening
In cystic fibrosis, inherited defects in the production or function of the CFTR protein lead to the buildup of thick and sticky mucus, particularly in the lungs, causing tissue damage. Changes to the structure of airway passages in CF lungs — such as the abnormal thickening of the airway walls, known as bronchiectasis — can be seen by MRI.
Trikafta is a triple combination CFTR modulator therapy, containing elexacaftor, tezacaftor, and ivacaftor, that’s designed to fix defects in both CFTR production and function. Approved for individuals carrying at least one copy of the most common CF-causing gene mutation — called F508del — clinical trials have demonstrated that Trikafta can significantly improve lung function, nutritional status, and quality of life for patients.
To learn more about Trikafta’s effects in the real world, researchers in Italy now examined the medical records of 19 adolescents and adults with CF. The 12 males and seven females, ages 12 and older, had undergone six months of treatment. The goal of the analysis was to understand Trikafta’s impact on both lung function and structure.
A composite chest MRI score was calculated that included various abnormal features seen in CF lungs. This included bronchial (airway) wall thickening, mucus plugging, abscesses or pus, and consolidations — the buildup of fluid or debris in the airways.
Before starting Trikafta, 10 of the patients had been treated with Orkambi (ivacaftor/lumacaftor) and one with Symdeko (ivacaftor/tezacaftor; Symkevi in the European Union). These are two other types of CFTR modulators.
After six months of Trikafta, the overall median MRI scores significantly dropped from 13 to 4, primarily due to reduced bronchial wall thickening and fewer lung consolidations.
Consistently, median scores for bronchiectasis/wall thickening changed from 8 to 3, while consolidation scores dropped from 1 to 0. Mucus plugging scores decreased from 3 to 0.
Alongside these structural benefits, lung function significantly improved. This included gains in FEV1, the amount of air forcibly expelled for one second, and FVC, the total amount of air expelled after one breath. Still, FEV1 measures did not correlate with MRI scores before or after treatment.
Trikafta also significantly improved body mass index (BMI), a measure of weight relative to height — more so in males than females. The patients’ sweat chloride levels, which are elevated in CF and indicate CFTR dysfunction, were significantly reduced with six months of treatment, as were pulmonary exacerbations, a sudden worsening of lung symptoms.
Quality of life, as assessed with the CF questionnaire revised (CFQ-R), showed no treatment-related changes.
MRI identifies longitudinal changes in lung structural damage after therapy, representing a safe and sensitive imaging modality for monitoring CF patients over time.
According to the researchers, because more than half of the study participants had already been treated with other CFTR modulators, their CFQ-R scores were higher before Trikafta compared with treatment-naive patients.
“The earlier initiation of modulators had already contributed to certain improvements,” they wrote.
Subgroup analysis revealed that patients with one F508del mutation had a greater drop in sweat chloride levels and a more marked improvement in quality of life than patients with two F508del defects.
“Our study well confirms … [that Trikafta] results in marked improvements in pulmonary abnormalities, particularly in bronchial wall and mucus plugging, along with benefits on pulmonary function and nutritional status,” the team concluded, noting also the usefulness of MRI scans in this patient population.
“MRI identifies longitudinal changes in lung structural damage after therapy, representing a safe and sensitive imaging modality for monitoring CF patients over time,” they added.