Weight gain on Kaftrio driven by fat, low-density muscle: Study

Researchers note need to monitor body composition, diet

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Treatment with Kaftrio (elexacaftor/tezacaftor/ivacaftor) led to gains in body mass among cystic fibrosis (CF) patients that were largely driven by increases in various types of fat and low-density muscles, a study found.

High-density muscle, which is stronger than its lower-density counterparts, didn’t change with the treatment, sold as Trikafta in the U.S. A higher amount of low-density muscle was linked to worse lung function, although patients generally experienced lung function gains regardless.

The study, “Impact of CFTR Modulator Therapy on Body Composition as Assessed by Thoracic Computed Tomography: A Follow-Up Study,” was published in Nutrition.

As fat gain and obesity are growing concerns among the treated CF population, the researchers said the findings highlight the “essential” need to continuously monitor body composition. “Future multicenter studies will be indispensable to assess the implementation of hygienic-dietary interventions aimed at enhancing the nutritional quality of the diet,” they wrote.

CF patients commonly experience pancreatic insufficiency, meaning the pancreas does not release enough of the enzymes needed for digestion, which contributes to malnutrition and an inability to gain weight.

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Obesity in CF patients rising

Evidence suggests that CFTR modulator therapies like Kaftrio can improve patients’ nutritional status. Studies show that these treatments lead to increases in body mass index (BMI), a measure that looks at person’s weight relative to height.

But gaining too much weight could raise the risk of cardiovascular disease and other health problems. Research shows increased rates of rates of obesity in CF patients, which also requires careful monitoring.

Just looking at a person’s weight is not enough to accurately assess the effects of a treatment on body composition, according to researchers. Measures that more closely monitor specific changes in fat and muscle offer a more holistic picture, they say.

Researchers in Spain set out to use CT imaging to evaluate body composition changes among among 26 adults being treated with Kaftrio at their clinic in Madrid.

This technique, which can look at different types of fat and muscle, is gaining traction for body composition assessments, but hadn’t been used to look at the effects of CFTR modulators, according to the study’s authors. CT imaging is also believed to have a number of advantages over standard approaches, such as bioimpedance, in terms of sensitivity and the types of muscle mass it can evaluate.

Study participants, who had a median age of 28.8, were all being treated for pancreatic insufficiency. More than a third (38.5%) had previously used other CFTR modulators.

All participants underwent CT scans before starting Kaftrio, as a baseline, and again at a minimum of six months after initiating treatment. They also underwent bioimpedance analyses. Baseline data from CT scans generally correlated well with comparable measures using bioimpedance, a noninvasive way of measuring body composition and body fluid volumes.

Those whose body composition had a greater area of very low-density muscle, which the authors called VLMDA, at baseline tended to be older and have worse lung function, while normal-density muscle was associated with better lung function.

Patients had an increase in total BMI and lung function with Kaftrio, as observed in previous studies.

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Muscle quality as well as quantity

CT scans showed that changes in overall body mass were largely driven by increases in various types of fat tissue, while overall muscle mass was not significantly changed. Among muscle subtypes, only the VLMDA compartment was significantly increased with treatment.

Moreover, a greater VLDMA at baseline was found to be a significant risk factor for having reduced lung function after six months of Trikafta treatment, as were prior CFTR modulator use and more subcutaneous (under-the-skin) fat.

While patients with more very low-density muscle had lower lung function at baseline and after being on treatment, patients generally experienced lung function improvements regardless of VLDMA changes.

“These findings remark the significance of muscle quality, in addition to quantity, in CF patients,” the researchers wrote. “Multidisciplinary treatment is pivotal in managing CF, and strategic approaches that include dietary counseling and exercise prescription are essential for improving body composition and nutritional status to prevent long-term complications,” they wrote.

The scientists said the small number of participants and the fact that most patients included were not undernourished before therapy and had normal weight indicate that “the results obtained may not be generalizable to CF populations with malnutrition.”