Trikafta improves sinus issues in CF patients after lung transplant: Study
Drug interactions should be considered when starting therapy in this population
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Trikafta (elexacaftor/tezacaftor/ivacaftor) is generally effective at easing sinus issues in people with cystic fibrosis (CF) who have already undergone a lung transplant, but more research is needed to evaluate whether it can improve nutritional status or lung function in transplant recipients, according to a new analysis.
Researchers also highlighted the importance of carefully considering drug interactions when starting Trikafta in transplant recipients, noting that patients often need adjustments of the medications used to manage the transplant.
The study, “Safety and extrapulmonary effects of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis following lung transplantation: A systematic review and meta-analysis,” was published in Paediatric Respiratory Reviews.
Trikafta increases functionality of defective CFTR protein
CF is a genetic disease marked by mutations in the gene that encodes CFTR, a protein that’s essential for regulating the movement of certain salt molecules and water in and out of the cell.
This movement is essential for mucus production, so a lack of functional CFTR leads to the production of thick, sticky mucus that builds up and causes damage to the lungs and other organs. In some cases, CF-related lung disease may become so severe that patients require a lung transplant.
Trikafta, sold in Europe as Kaftrio, is a combination of three CFTR modulators, which are molecules that can increase the functionality of the defective CFTR protein in people with CF caused by certain mutations. The oral therapy is widely approved to treat CF patients with eligible mutations, based primarily on data showing that it can increase lung function in CF patients who have not had a transplant.
People with CF who have undergone a lung transplant are rarely given Trikafta, as the therapy is not expected to affect lung health in transplanted recipients. Still, lung problems are only one facet of how CF affects the body.
Trikafta may potentially help address other disease symptoms, ranging from sinus issues to digestive problems, in transplant patients. But studies examining how Trikafta treatment can affect these issues in CF patients are scarce.
Dose adjustments in transplant recipients were often minimal
In this study, an international team of scientists reviewed the published medical literature for reports on Trikafta use in transplant recipients. The scientists identified eight studies reporting outcomes from 195 patients. The most commonly documented reasons for initiating Trikafta were sinus disease and digestive complaints.
The researchers noted that transplant recipients starting Trikafta often had to undergo adjustments in doses for other therapies that they were using to manage the health of the transplanted lungs. Although more than half of patients had some dose adjustments, these were “often minimal,” the researchers noted.
The scientists underscored the importance of carefully considering potential drug interactions when a transplant recipient is starting any new medication.
Safety issues reported among the transplant recipients were in line with the known profile of Trikafta in the broader population of people with CF. The most common side effects were digestive complaints such as nausea and diarrhea, mood changes, and skin rash.
Across all the studies, rhinosinusitis was one of the major indications for the start of [Trikafta] treatment, with the majority showing an improvement.
Results showed that Trikafta was effective in easing rhinosinusitis, or inflammation of the nose and sinuses caused by stagnant mucus.
“Across all the studies, rhinosinusitis was one of the major indications for the start of [Trikafta] treatment, with the majority showing an improvement,” the researchers wrote.
Patients also tended to gain weight after Trikafta, though the average change wasn’t statistically significant in an analysis that pooled all available data. The researchers also highlighted substantial variation in outcomes across studies, so they said further research is needed to evaluate these effects on weight more conclusively.
A pooled analysis also indicated that Trikafta led to a small but statistically significant improvement in lung function among the transplant recipients. Still, the researchers cautioned that this analysis was limited to a small number of patients and that, again, there was variability across studies.
“Further studies with longer [follow-up] and closed monitor after [Trikafta] start are needed to demonstrate any significant effect of [Trikafta] in lung function,” they said.
Broadly, these data suggest that Trikafta may offer benefits for CF patients who have undergone a lung transplant, but further research is needed to fully assess its safety and efficacy in this population.
Vertex Pharmaceuticals sells Trikafta. The company was not involved with this study, which was funded in part by the Italian Ministry of Health.
