Trikafta cuts need long-term for other CF treatments in real world
Analysis: Patients able to to cut back on mucus-clearing therapies, antibiotics
After starting treatment with Trikafta, people with cystic fibrosis (CF) tend to have less need for inhaled mucus-clearing therapies and antibiotics, according to a new analysis of data from a real-world study.
Moreover, the reduced need for other medication while on Trikafta was found to continue over the long term, the data showed.
“This is incredibly meaningful for individuals and families living with CF,” Scott Sagel, MD, PhD, lead author of the study and director of the University of Colorado Cystic Fibrosis Center, said in a university news story detailing the findings of the study, which showed a “sustained decrease in respiratory treatment burden in those on [the triple-combination] therapy.”
“For decades people with CF have spent hours every day managing their disease,” Sagel said. “Our findings show that many have stepped back from some of those time-consuming therapies thanks to [Trikafta].”
The study, “Elexacaftor/tezacaftor/ivacaftor is associated with long-term reduction in use of chronic respiratory therapies in cystic fibrosis,” was published in the Journal of Cystic Fibrosis. The work was funded by the Cystic Fibrosis Foundation and the National Institutes of Health. Vertex Pharmaceuticals, the company that sells Trikafta, was not involved.
CF is caused by mutations in the gene that encodes CFTR, a protein crucial in regulating mucus production. In people with CF, a lack of functional CFTR causes the body to produce thick, sticky mucus that’s prone to accumulating in the lungs and other organs. This drives most disease symptoms and can set the stage for bacterial lung infection.
Management of CF commonly includes mucolytics — inhaled therapies that are used to help clear mucus from the airways — as well as antibiotics to control infections.
“For many families, the daily time commitment required for CF care can be overwhelming,” Sagel said. “Seeing people maintain good health while doing fewer respiratory therapies is incredibly encouraging. A reduction in treatment burden can have a profound impact on quality of life.”
Examining Trikafta use for up to 4.5 years in older patients, 3 in younger ones
Trikafta contains a combination of three CFTR modulators — elexacaftor, tezacaftor, and ivacaftor — a class of medications designed to boost the activity of the mutated protein in people with CF caused by certain mutations. It is widely approved for people with CF who have responsive mutations, including the most common CF-causing mutation known as F508del.
By boosting CFTR protein activity, Trikafta aims to help normalize mucus production. Clinical trials and real-world data have demonstrated that Trikafta treatment can lead to sustained improvements in lung function measures.
Now, a team of scientists in the U.S. and Canada sought to assess how Trikafta treatment impacts patients’ use of mucolytics and antibiotics. To that end, they conducted a post-hoc analysis, which is an examination of data that’s not planned out until after a study is finished and the findings are already available.
“The aim of this post-hoc analysis was to evaluate longer term changes in the use of chronic respiratory therapies following initiation of [Trikafta],” the researchers wrote. The team specifically focused on treatment use in U.S. patients for as long as 4.5 years after starting Trikafta for adolescents 12 and older and adults, and for up to three years in children ages 6-11.
The data came from a real-world study called PROMISE (NCT04038047), which tracked outcomes from hundreds of CF patients after they started on Trikafta. The analysis specifically focused on four types of treatments: two mucolytics, namely Pulmozyme (dornase alfa) and hypertonic saline, and two types of antibiotics, which were inhaled antibiotics and oral azithromycin.
Data from 479 individuals ages 12 and older showed that, prior to Trikafta, most patients (86%) were taking two or more of these supportive therapies. But after 4.5 years on the medication, more than half of all patients were taking one or none of these therapies.
More granular analyses showed reductions in the proportion of patients taking each of the four types of therapies: from 88% to 51% for Pulmozyme, from 76% to 44% for hypertonic saline, from 51% to 19% for inhaled antibiotics, and from 49% to 31% for oral azithromycin.
No declines in lung function nor more respiratory symptoms seen
Consistent results were also seen among the data from the younger patients — 124 children ranging in age from 6 to 11. Specifically, after three years on Trikafta, nearly 60% these children were taking one or zero supportive therapies, with decreases in the rate of patients taking each of the four types of treatment analyzed.
No safety concerns were noted in either age group, with the researchers stating that, overall, there were “no adverse effects of medication discontinuation on health outcomes.”
The reductions in the use of multiple supportive therapies did not lead to lung function decline or more respiratory symptoms, the team noted.
“These data indicate a significant decrease in respiratory treatment burden among [people with] CF on [Trikafta] therapy,” the scientists concluded.
The goal is to help people with CF and their care teams maintain strong long-term health while easing daily treatment demands.
Still, while Trikafta may help reduce the need for other treatments for people with CF in general, the scientists noted that each individual with CF is unique, and patients should collaborate closely with their care providers before making decisions about stopping the use of supportive therapies.
“The opportunity to simplify daily treatment is exciting but decisions to stop or continue therapies should be made through shared decision-making with a clinician who understands each person’s overall health,” Sagel said, adding that “the goal is to help people with CF and their care teams maintain strong long-term health while easing daily treatment demands.”
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