Kaftrio observed to improve lung, sinus structures on CT scans

Reductions in CF symptoms, gains in lung function also seen with treatment

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Structural improvements in the airways and sinuses of adults with cystic fibrosis (CF) were seen on CT scans after a year on Kaftrio, and occurred alongside reductions in CF symptoms and gains in measures of lung function, according to an Italian study.

“Imaging findings on CT during follow-up closely correlate with improved clinical scores and functional data,” wrote the researchers, who suggested the use of CT “as an objective measure of disease improvement.”

The study, “Radiological and clinical evaluation of triple combination modulating therapy effectiveness in adult patients with cystic fibrosis,” was published in Meta-Radiology.

“Future larger prospective studies that can objectively confirm this suggestion are warranted,” the researchers said.

CF is caused by genetic mutations that change the way the CFTR protein works or how much of it is made. Kaftrio, branded as Trikafta in the U.S., contains three CFTR modulators — elexacaftor, tezacaftor, and ivacaftor — which help the faulty protein fold correctly and work more effectively.

Kaftrio is approved in the European Union in combination with Kalydeco (ivacaftor) for patients carrying at least one copy of F508del, the most common CF-causing mutation, It was shown in clinical trials to result in better lung function, nutritional status, and quality of life.

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Kaftrio’s effects in CF

MRI studies have found that Kaftrio also improves structural abnormalities in the airways, thinning the thickened airways and clearing the mucus plugs that block airflow.

While “CT is highly sensitive in the detection of structural lung damage,” few studies have used it to measure treatment improvements in the airways and sinuses, the air-filled spaces in the bones of the face.

The study included 44 adults (24 women, 20 men), mean age 30.4, with a diagnosis of CF. They underwent chest CT scans before and one year after starting Kaftrio.

The Brody II score (BIIS) was used to record mucus plugging, airway wall thickening, bronchiectasis (widened airways), damage to the parenchyma (the lung’s functional tissue), and trapped air, or hyperinflation. Each was scored on a scale from 0 to 100, with a higher score indicating worse disease.

Mean total BIIS decreased significantly from before to one year after starting Kaftrio (21.4 vs. 15.4 points), indicating structural improvements in the airways. Significant decreases were observed in mucus plugging (28.1 vs. 12.3 points), airway wall thickening (34.7 vs. 18.5 points), and damage to the parenchyma (2.5 vs. 2.2 points).

The severity of sinus disease was evaluated using the Lund-Mackay and the Sheikh-Lind CT severity scoring systems, where a higher score indicates worse disease. Both showed significant improvements after a year on Kaftrio.

Mean scores about halved over a year in the 22-item Sinonasal Outcome Test (SNOT-22), a patient-reported outcome measure for chronic rhinosinusitis, a long-lasting inflammation of the nose and sinuses, indicating fewer symptoms (29.5 vs. 14.7 points).

Measures of lung function also improved, with a significant increase in the mean percent predicted forced expiratory volume in one second, or FEV1 (84.9% vs. 71.8%), and mean percent predicted forced vital capacity, or FVC (95.4% vs. 83.3%). Both FEV1 and FVC are measures of the amount of air a person is able to exhale.

Changes in total BIIS correlated with changes in FEV1, that is, the greater the drop in total BIIS, the greater the increase in FEV1. The same was observed between changes in total BIIS and FVC, but the correlation wasn’t as strong.

The findings suggest that changes in CT imaging results align with clinical and functional outcomes, indicating CT may serve as an objective measure for monitoring patients being treated with Kaftrio.

“To our knowledge, this is the study with the largest CF patient population with lung disease that was assessed using CT scores, clinical and functional parameters before and one year after [Kaftrio] therapy,” wrote the researchers, who noted that a reduction in lung disease after a year with a CFTR modulator “does not prove with absolute certainty that the treatment works, as potentially confounding factors that could have contributed to a decrease in lung disease in this patient cohort were not actively investigated.”