Kaftrio improves lung function in cystic fibrosis children in real world

Study shows therapy, sold as Trikafta in North America, was well tolerated

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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In a real-world study involving children with cystic fibrosis (CF) in Italy, Kaftrio — an approved CF therapy sold as Trikafta in North America — was shown to lead to significant improvements in lung function for more than 30 youngsters.

The study’s researchers say their findings offer data “beyond the controlled setting of clinical trials,” and that the work, moreover, “provides evidence regarding the effectiveness of [Kaftrio] treatment in improving early signs of lung damage” in CF children.

“Our data indicate that [Kaftrio] therapy is well tolerated by children with CF and is effective in improving signs of lung function abnormalities from early childhood,” the researchers wrote.

Titled “Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor treatment in children aged 6-11 years with cystic fibrosis in a real-world setting,” the study was published in the journal Pediatric Pulmonology.

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Real-world data ‘scanty’ on Kaftrio impact in cystic fibrosis children

CF is caused by mutations in the CFTR gene, resulting in missing or dysfunctional CFTR — a protein that regulates the movement of chloride in and out of cells. This results in the accumulation of thick and sticky mucus in organs such as the lungs, pancreas, and liver, causing most disease symptoms.

Treatment with Kaftrio (elexacaftor/tezacaftor/ivacaftor), a CFTR modulator therapy that helps increase the protein’s functionality, has been found to significantly improve lung function and to reduce the frequency of exacerbations, or periods of sudden symptom worsening, in patients. The therapy also has been shown to improve quality of life and nutritional status for people with CF.

However, although cystic fibrosis children are of particular interest as treatment may prevent lung disease progression, “real‐world data on the effectiveness and safety of [Kaftrio] therapy in the pediatric population … are scanty,” the researchers noted.

To that end, a team of scientists from Italy analyzed the safety and efficacy of Kaftrio in 34 children with cystic fibrosis treated at a CF center in Milan. The patients had a median age of 8.3 years and nearly two-thirds (64.7%) were boys. The majority (67.6%) had an F508del mutation combined with a minimal function variant, or a mutation in which the resulting CFTR protein works minimally.

Before Kaftrio therapy, all patients had pancreatic insufficiency, which occurs when the pancreas does not release enough of certain enzymes needed for digestion. Most exhibited normal lung function, as assessed by their percent predicted forced expiratory volume in one second (ppFEV1). About 85% had abnormal lung clearance index values — results of a test of lung function that measures how long it takes for a tracer gas to be cleared from the lungs.

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Lung exacerbations were reduced by 40% after 6 months

After 24 weeks or about six months of treatment with Kaftrio, sweat chloride  typically high in CF patients  was reduced by an average of 63 milliequivalents per liter (mEq/L), with 70.6% of patients reaching sweat chloride levels below the threshold that indicates CF (60 mEq/L).

Treatment significantly improved lung function, as it significantly increased the patients’ ppFEV1 (average of 8.8 points after 24 weeks) and decreased lung clearance index (2.3 units after 12 weeks).

A total of 57 lung exacerbations in 26 children (0.28 per patient-month) were observed after six months, compared with 97 (0.48 per patient-month) seen before Kaftrio was started. This corresponded to a 41% reduction.

Respiratory exacerbations were defined as those requiring oral or intravenous (into-the-vein) antibiotic therapy, characterized by at least two of the following signs: fever, cough, increased sputum (phlegm), loss of appetite, symptoms of upper respiratory tract infection, and missing school due to illness. These symptoms had to be associated with decreased lung function, an increase in respiratory rate, or increased levels of neutrophils, a type of immune cell.

A slight increase of 0.15 in body mass index  a measure of body fat based on weight and height — was seen after 24 weeks.

The study is based on real‐world data generated during routine clinical practice, confirming in children with CF the results observed in randomized clinical trials.

Regarding treatment safety, the most common adverse events were lung exacerbations (76.5%), self-limiting skin rash (17.6%), and ear infection (8.8%). Two children had severe events requiring hospitalization for antibiotic therapy.

Limitations of the study, according to team members, included the relatively small number of patients and the short-term follow-up period.

“The study is based on real‐world data generated during routine clinical practice, confirming in children with CF the results observed in randomized clinical trials,” the researchers wrote.

Overall, according to the team, there was “a significant improvement in lung function … and an approximately 40% reduced rate of pulmonary exacerbations.”