Trikafta led to greater drop in lung exacerbations in men than women

Trikafta may not be able to remove CF disparities between sexes, study suggests

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Men with cystic fibrosis (CF) saw greater reductions in lung symptom exacerbations after starting treatment with Trikafta (elexacaftor/tezacaftor/ivacaftor) than their female counterparts, according to a recent study.

Changes in nutritional status, lung infections, and lung function were similar between the sexes.

The findings overall suggest that high-efficacy therapies like Trikafta may not be able to completely eliminate the known disparities in disease progression between men and women with CF.

More research is needed to understand sex differences in CF progression and treatment responses, researchers note.

“By understanding the different effects that [Trikafta] has on females versus males, we will be able to make more informed clinical decisions about how best to maintain health and aggressiveness of treatment in people with CF to ensure the most optimal outcomes,” researchers wrote.

The study, “Sex differences in outcomes of people with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor,” was published in the Journal of Cystic Fibrosis.

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Patients able to reduce supportive therapies after starting Trikafta

Research indicates women with CF experience more severe outcomes

While CF is equally prevalent among male and female patients, a body of evidence indicates that women experience more severe disease outcomes.

Particularly, studies have shown that women have more pulmonary exacerbations — acute worsening of lung symptoms — an earlier need for lung transplant, more antibiotic-resistant lung infections with Pseudomonas aeruginosa, and a shorter life expectancy relative to men.

Still, much of these data were collected prior to the widespread use of highly effective CFTR modulator therapies. The emergence of the triple combo therapy Trikafta in recent years has “dramatically changed the landscape,” according to the researchers.

With patients now living longer and healthier lives on these treatments, “the question remains as to whether females with CF will continue to fare worse than males,” they wrote.

To learn more, the researchers examined medical records from CF patients prescribed Trikafta and followed at the University of Texas Southwestern Medical Center from January 2014 to September 2022.

These 251 participants — 110 women and 141 men — were followed for about 5.5 years before and about 2.5 years after starting Trikafta.

By understanding the different effects that [Trikafta] has on females versus males, we will be able to make more informed clinical decisions about how best to maintain health and aggressiveness of treatment in people with CF to ensure the most optimal outcomes.

Women were older, leaner than men when they started Trikafta treatment

Female patients were significantly older than male patients when they started on Trikafta, and had a lower mean body mass index (BMI), a measure of body fat.

Other factors, including lung function at the last visit before starting Trikafta, frequency of P. aeruginosa infectionsand pulmonary exacerbations were similar between groups.

With Trikafta, the frequency of pulmonary exacerbations was significantly higher in women than in men, but other clinical factors were similar.

In final statistical analyses, changes in lung function, rates of P. aeruginosa infections, and BMI after starting treatment did not significantly differ between sexes.

However, the change in pulmonary exacerbations did differ, with men seeing a greater drop in their occurrence than did women.

Specifically, while men experienced a 43% reduction in exacerbations after starting Trikafta, women experienced a 25% reduction.

In the subset of patients who had no previous history of CFTR modulator use before using Trikafta, women tended to see less change in pulmonary exacerbations and lung function with treatment than men, but these findings failed to reach statistical significance.

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Trikafta may potentially amplify sex disparity in CF in some populations

Altogether, “these data suggest that [Trikafta] will not narrow the sex disparity in CF and potentially amplify it in some populations,” the researchers wrote.

The reasons underlying sex differences in CF haven’t been entirely worked out, and will require additional study, they noted.

Research suggests that certain sex hormones, like estrogen, might influence inflammation as well as the CFTR protein that’s defective in CF to modulate disease.

Likewise, the reasons why responses to Trikafta might be different between sexes also remains to be determined.

Given the evidence that CFTR modulators like Trikafta may not close sex disparities in CF, “we must continue to understand the mechanism behind the sex disparity to seek other therapies that may target this sex specific difference,” the researchers wrote.