School-age children with cystic fibrosis benefit from Trikafta
Reduced lung structure abnormalities, improved function observed
One year of Trikafta treatment improved lung function, reduced abnormalities in lung structure, and halted disease progression among school-age children, ages 6-11, with cystic fibrosis (CF), according to a real-world analysis.
“The majority of the children even achieved normal lung function with the triple combination therapy. That’s a highly positive result!,” Marcus Mall, MD, director of the department of pediatric respiratory medicine, immunology and critical care medicine at Charité-Universitätsmedizin Berlin, in Germany, said in a university press release.
The study, “Impact of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Children with Cystic Fibrosis and One or Two F508del Alleles,” was published in the European Respiratory Journal.
People with CF experience an abnormal buildup of thick, sticky mucus in the lungs, clogging the airways. This leads to shortness of breath, chronic bacterial infections, inflammation, and lung tissue changes, all of which compromise lung function. Symptomatic treatment involves inhaling mucus-thinning medications every day and antibiotics in cases of infection.
Trikafta, by Vertex Pharmaceuticals, is a combination of three CF medications, elexacaftor, tezacaftor, and ivacaftor, approved for CF patients as young as age 2. The therapy is disease-modifying, meaning it’s designed to improve the production and function of the CFTR channel protein, the underlying cause of CF.
“Triple combination therapy makes it possible to boost the functioning of the CFTR channel to as much as 50 percent of normal levels,” said Mirjam Stahl, MD, the study’s corresponding author and head of the division of cystic fibrosis at the department of pediatric respiratory medicine, immunology, and critical care medicine at Charité. “We know from a previous observational study of adults that the triple combination therapy is associated with considerable improvement in lung function and quality of life. It’s a true game changer for the majority of patients,” Stahl said.
Effect of Trikafta on school-age children
Here, a research team led by Stahl and Mall sought to assess the real-world effectiveness of Trikafta in elementary school children.
“Real-world data on the effect of [Trikafta] on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported,” the researchers said.
A total of 107 children with CF, aged 6-11, were analyzed. Among them, 67 carried two copies of F508del (F/F), the most common CF-causing mutation, and 40 had an F508del mutation and a minimal function mutation (F/MF), that is, a mutation wherein the resulting CFTR protein works minimally.
MRI scans looked for abnormalities in lung tissue structure and lung function was assessed by the lung clearance index (LCI), a test that measures how long it takes a tracer gas to be cleared from the lungs. LCI was assessed for up to 12 months and lung MRIs were conducted before and three months after starting Trikafta.
According to the researchers, MRI scans made it possible to visualize changes in the lungs such as the widening and thickening of the airways, and persistent mucus deposits.
Treatment with Trikafta significantly improved the LCI in both F/F and F/MF children with CF from three months onwards, data showed. It also significantly improved the MRI global scores in F/F and F/MF patients.
“Our results support early initiation of [Trikafta] to reduce or even prevent lung disease progression in school-age children with CF,” the researchers said.
“Having this therapy become available for children is a real blessing for our young patients,” said Stahl, whose team is conducting a similar real-world study of children ages 2-5. “We were able to show that triple combination therapy leads to a significant improvement in the lung disease.”
“We hope starting triple combination therapy in early childhood will be able to prevent the emergence of severe symptoms and the formation of structural changes in the lungs,” Stahl said.
The researchers also want to know if Trikafta can reduce the need for symptom-based therapy.
“Needing fewer inhalations would be a huge time saver for patients in day-to-day life and significantly improve their quality of life,” Stahl said.
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