CF treatment Trikafta boosts lung function for patients over 40
Study assesses effects in patients older than those in clinical trials
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Trikafta safely improved lung function and reduced exacerbations in people with cystic fibrosis (CF) who started treatment after age 40, a study found.
Some participants no longer had Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus (MRSA), bacteria that are major contributors to CF lung disease.
“Overall, our study is unique in its way that we focus on “aged” [CF population] showing still benefit from [Trikafta] but to a lower degree compared to younger patients in previous studies,” the researchers wrote.
The study, “Assessment of efficacy and tolerability of elexacaftor-tezacaftor-ivacaftor in an observational cohort study of “aged” people with cystic fibrosis,” was published in Therapeutic Advances in Respiratory Disease.
CF is caused by mutations in the CFTR gene that result in the loss or dysfunction of the same-named protein. This leads to the production of thick, sticky mucus that accumulates in the lungs, digestive system, and other organs, driving CF symptoms.
Trial participants tend to be younger
Trikafta is a combination of three CFTR modulators — elexacaftor, tezacaftor, and ivacaftor — medications that can improve the function of the CFTR protein in patients carrying certain disease-causing mutations. Clinical trials and real-world evidence have shown that the treatment leads to significant improvements in lung function, decreased risk of worsening lung symptoms, and weight gain.
However, participants in the trials that supported regulatory approvals had a mean age in the mid- to late 20s, suggesting that data from older patients are limited.
To learn more, researchers assessed CF patients who started taking Trikafta after age 40 at the University of Alabama’s Adult CF Clinic. Forty-two patients, with a mean age of 47.9 at treatment initiation, took part. Most (88%) had at least one copy of the F508del mutation.
Body mass index (BMI), a measure of body fat based on weight and height, and lung function were assessed before, and at three and nine to 15 months after, Trikafta therapy was started. Researchers assessed lung function using the percent predicted forced expiratory volume in 1 second (ppFEV1), which compares how much air one can forcefully exhale with what’s expected for individuals of similar age, sex, ethnicity, and height.
Before treatment, patients had a mean ppFEV1 of 58.4%, which increased by 0.24% per month and nearly 3% per year on Trikafta. Participants with CF-related diabetes started with poorer lung function and experienced greater improvements with treatment, but the differences were not statistically significant.
The number of CF exacerbations, defined as either antibiotic initiation or hospitalization, decreased significantly after starting treatment, from 1.5 in the year before starting Trikafta to 0.5 after 9-15 months on the therapy.
Most of the 35 patients with available data tested positive for P. aeruginosa, MRSA, or multiple bacterial species (usually P. aeruginosa and MRSA) before treatment. Trikafta led to a decrease in the number of people testing positive for both species, despite more patients testing positive for either P. aeruginosa or MRSA.
“Our results are encouraging, since chronic coinfections, especially with MRSA and [P. aeruginosa], are correlated with significantly more rapid lung decline and higher frequency of [intravenous] antibiotic use,” the researchers wrote.
Ten patients were underweight at baseline; three met the CF Foundation‘s weight guidelines after Trikafta. Nineteen were overweight or obese, “which will lead to counseling in a clinic appointment about weight loss and maintaining a healthy weight,” the scientists wrote. Results showed a significant, but slight, monthly increase in BMI with Trikafta.
Trikafta was well tolerated, with no patient discontinuing therapy.
“We can conclude that [Trikafta] was safe for the [patients] we studied at an advanced age and with generally lower lung function, and they still received the benefits like other previously studied cohorts,” the team concluded. “It will be important to continue extending those studies to other centers for more patients and even older ages to draw comprehensive conclusions about the risk and benefit of highly effective modulator therapies in general in an aging CF population.”
