Kaftrio helps CF adults build fat stores, boost muscle mass: Study

Findings may have implications for nutritional management

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with Kaftrio (elexacaftor/tezacaftor/ivacaftor) helps increase fat stores in adults with cystic fibrosis (CF), especially those who are underweight, a study found.

Researchers also found small, though statistically significant, increases in muscle mass in patients who started on Kaftrio.

The results showed that Kaftrio mainly affects fat tissues, “and, to a lesser extent, muscle parameters in [adults with] CF,” the researchers wrote.

The findings “may have implications for the future nutritional management of [people with] CF,” they wrote in the study, “Elexacaftor/tezacaftor/ivacaftor influences body composition in adults with cystic fibrosis: a fully automated CT-based analysis,” published in Scientific Reports.

CF is caused by mutations in the gene that provides instructions to make the CFTR protein. Without a functional protein, abnormally thick and sticky mucus builds up in the body. This mucus can block the normal secretion of enzymes needed for digestion, making it harder for the body to extract nutrients from food. As a result, difficulty gaining weight is a common symptom of CF.

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Kaftrio, sold as Trikafta in the U.S., contains a combination of three CFTR modulators, which are medications that can boost the functionality of the faulty CFTR protein in people with certain disease-causing mutations. There’s accumulating data that adults with CF who start on Kaftrio tend to gain weight — but are these patients adding fat stores, putting on muscle mass, or both?

To answer that question, a team of scientists in Germany used CT scans of the chest to measure the fat and muscle content in 66 adults with CF before and after starting on Kaftrio.

“We used fully automated CT-based BCA [body composition analysis] to investigate the impact of CFTR modulator therapy on thoracic bone, muscle and adipose [fat] tissues,” the scientists wrote. Chest CT scans, commonly done in CF clinical practice to look at the lungs, can be used to assess body composition as well, they noted.

In line with data from other studies, the study found the patients tended to gain weight after starting on Kaftrio. Prior to treatment, nearly one in three was classified as underweight based on body mass index (BMI, a ratio of weight to height). But after Kaftrio, fewer than one in ten was classified as underweight. Likewise, the number of patients whose BMI classified them as overweight increased from 8% before Kaftrio to 14% with the therapy.

Results from CT scans showed that Kaftrio led to an increase in fat stores. The average total adipose ratio increased by 46%. The increase in body fat stores was especially pronounced in patients who were underweight before starting treatment, the researchers said.

“The highest gains in adipose tissue ratios were observed in individuals [who were] underweight at [Kaftrio] initiation, while [people with] CF with normal-/overweight experienced modest increases of adipose tissue ratios,” they wrote.

There also was a small (less than 2%) increase in muscle ratio after starting Kaftrio. Though this increase was numerically small, analyses suggested it was statistically significant, meaning the result was unlikely to be random chance.

“The marginal gains in muscle ratio were surprising,” the researchers wrote. They noted that, since the study used CT scans of the chest, it may have achieved its results because Kaftrio can improve lung function for eligible CF patients, which could lead to less strain for muscles in the chest. Since they didn’t have data for other parts of the body, they highlighted a need for further investigation.

Kaftrio is sold by Vertex Pharmaceuticals, which was not involved in the study.