Trikafta Treatment Clears Aspergillus Fungus in CF: Pilot Study
Fewer sputum samples were positive for fungus after treatment compared to before
Trikafta, a triple therapy combining elexacaftor, tezacaftor, and ivacaftor, cleared Aspergillus fungus in the lungs and prevented severe infections in children and adults with cystic fibrosis (CF), a pilot study found.
“These preliminary results are very encouraging and support the hypothesis that initiation of [Trikafta] therapy rapidly improves Aspergillus lung clearance in patients with CF,” the researchers wrote, noting larger studies of longer duration are needed to reinforce these “promising results.”
The study, “Advent of elexacaftor/tezacaftor/ivacaftor for cystic fibrosis treatment: What consequences on Aspergillus-related disease? Preliminary insights,” was published as a letter to the editor in the Journal of Cystic Fibrosis.
CF is caused by defects in the CFTR protein that regulates the transport of water and salt through cells. These defects lead to thick, sticky mucus building up in organs such as the lungs and predispose patients to severe bacterial and fungal infections, often causing hospitalizations.
CFTR modulators, one of the treatments available for CF, are designed to improve defective CFTR proteins’ function. There are two main types — correctors, which assist CFTR proteins’ folding and cellular transport, and potentiators, which enhance the possibility of holding the opening of the CFTR channel at the cell surface. Trikfata contains both types of therapies.
Clinical trials have shown Trikafta improves lung function, lowers lung exacerbations, and helps reduce the number of hospital visits due to bacterial infections, among other benefits. Little is known about its impact on fungal infections, however.
Scientists analyzed sputum samples collected from 58 CF patients — 15 children and 43 adults. The samples were collected from two years before to one year after starting Trikafta. They were cultured to check for Aspergillus infections and levels of immunoglobulin E (IgE, a type of antibody) and Aspergillus fumigatus-specific IgE in blood samples were measured.
Fewer sputum samples were positive for Aspergillus after Trikafta treatment compared to those collected before treatment in all patients.
“This may be due in part to CFTR restoration, which is associated with enhanced mucociliary clearance, but also to CFTR modulators which dampen Aspergillus-induced reactive oxygen species,” the scientists wrote. Mucociliary clearance is a defense mechanism that results in mucus and harmful substances being clear from the airways. Reactive oxygen species cause oxidative damage when they outweigh the body’s antioxidant defenses.
Total IgE antibodies were also significantly reduced after Trikafta treatment, but there was no change in Aspergillus-specific IgE levels.
The scientists suggest interpreting the antibody results with caution. Since patients visit hospitals infrequently when taking effective treatments such as Trikafta, routine blood tests are more spaced out and may not accurately reflect total or Aspergillus-specific IgE levels.
Overall, “we can expect that yesterday paradigms on the fungal impact in CF is about to change in a near future. As a consequence, the follow-up of CF patients and treatment habits could be profoundly transformed and lead to antifungal therapy abstention,” the scientists wrote.