Trikafta benefits seen regardless of prior CFTR modulator use for CF
Real world study shows approved medication eased symptoms over 1 year
One-year treatment with Trikafta — a widely used, approved medication for people with cystic fibrosis (CF) — significantly eases symptoms and improves outcomes, regardless of whether or not patients were previously treated with other CFTR modulators, a new real-world study reports.
Among other benefits, Trikafta — a combination of elexacaftor, tezacaftor, and ivacaftor — improved lung function, helped reduce chronic sinus problems, and lessened the need for other therapeutic interventions, according to the study’s findings.
“Our study suggests that [the] real-world impact of [Trikafta] on clinical parameters and structural changes in sinus disease [is] not impacted by previous exposure to CFTR modulators,” the team of U.S. researchers wrote.
Titled “Real -World impact of previous exposure to CFTR modulators on clinical parameters and chronic sinus disease in people with cystic fibrosis on elexacaftor-tezacaftor-ivacaftor,” the study was published in the journal Respiratory Medicine.
Mutations in the CFTR gene, which result in no or faulty CFTR protein, are the cause of CF. A channel protein, CFTR helps control how charged molecules move across the cell membrane.
Without functional CFTR, the body produces abnormally thick, sticky mucus, which can build up in organs. This leads to symptoms that can include respiratory and digestive problems.
CFTR modulators are a category of medications that aim to improve the function of the CFTR protein in eligible people with CF.
Testing ‘perception’ that CFTR modulator use hampers Trikafta gains
In the U.S., eligible patients are those ages 2 and older who carry one F508del mutation or a non-F508del mutation in the CFTR gene that’s responsive based on clinical and/or lab test data
“There is a perception that those previously exposed to CFTR modulators … may have gained some benefits from [such treatment] and thus their improvement in clinical outcomes may be less prominent compared to those who are naïve to [or have never been treated with] CFTR modulators,” the researchers wrote.
To better understand whether previous treatment with other CFTR modulators affects the benefit of Trikafta medication, a team of scientists assessed 115 people treated at Nationwide Children’s Hospital in Ohio. Slightly more than 40%, or 49 patients, had not previously taken CFTR modulators. The other nearly 60%, or 66 patients, had previously used other therapies, including Orkambi (lumacaftor/ivacaftor), Symdeko (tezacaftor/ivacaftor), and Kalydeco (ivacaftor).
There were some differences between the groups at the beginning of Trikafta treatment, the researchers noted. Those who had previously taken Symdeko were significantly older than those without prior use of a modulator therapy (median age 27 vs. 20). Also, participants previously treated with other CFTR modulators were significantly more likely to have two copies of the F508del mutation.
Body mass index (BMI), a measure of body fat that takes into account weight and height, was significantly lower in the group without previous exposure, suggesting poorer nutritional status, the scientists noted. However, “the difference was no longer significant at [three]-month follow up and both groups had similar improvement in BMI after one year of study,” the team wrote.
Improvements seen in sinus CT scans for subset of CF patients
Alongside increases in BMI, both groups saw a significant improvement after a year of treatment in percent predicted forced expiratory volume in one second, or ppFEV1, a measure of lung function. Hospital admissions decreased significantly in the two groups, as did the need for antibiotic treatment and chest therapy. The number of pulmonary flare-ups among patients also dropped.
No patient required sinus surgery or into-the-vein, or intravenous, antibiotic therapy for acute rhinosinusitis — inflammation of the nasal cavity and paranasal sinuses — during the study.
[Trikafta] therapy was associated with improved clinical outcomes and improvement in sinus CT scans in [people with] CF and changes were independent of [the use of] previous CFTR modulator therapies.
A subset of 21 participants had CT scans at the start and end of treatment to assess sinus disease. On two scoring systems, the results indicated improvement after Trikafta.
At the end of the study, “there was no significant difference in any of the clinical parameters between those naïve vs. previously exposed to other CFTR modulators,” the researchers wrote.
That led the researchers to conclude that Trikafta “therapy was associated with improved clinical outcomes and improvement in sinus CT scans in [people with] CF and changes were independent of [the use of] previous CFTR modulator therapies.”
The study’s limitations included the relatively small sample size and that patients were treated at a single center. Further, there was no control group, and there was a lack of subjective metrics such as changes in quality of life, the researchers noted.
The finding that prior CFTR modulator exposure doesn’t impact Trikafta’s effects could have implications for other therapies as well, according to the team.
“This may also suggest that any future CFTR modulators may also be independent of exposure to previous CFTR molecules,” the researchers wrote.
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