In CF, body composition may assess weight gain better than BMI

Use of medicines like Kaftrio has raised concerns about obesity in patients

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Body composition assessments, particularly fat mass and fat-free mass, may be more informative than body mass index (BMI) for monitoring weight gain in cystic fibrosis (CF) patients starting Kaftrio (elexacaftor/tezacaftor/ivacaftor), a Welsh real-world study suggests.

The researchers found that while patients’ BMI, a ratio of weight to height, significantly increased after a median of seven months on Kaftrio, body composition measurements revealed sex-specific trends. These included a greater increase in fat-free mass in men and a greater percentage of women showing normal weight, but excess body fat.

With a growing trend of overweight and obesity with prolonged survival among CF patients, routine body composition assessments can help identify those “with elevated [fat mass] or depleted [fat-free mass], enabling individualized care with the focus of optimizing [body composition],” the researchers wrote in “Weight a minute: Exploring the effect on weight and body composition after the initiation of elexacaftor/tezacaftor/ivacaftor in adults with CF,” which was published in the Journal of Cystic Fibrosis.

Along with lung function, CF can affect digestive health, making it difficult for many patients to get enough nutrients from their food. As such, high fat, high calorie diets have been recommended for reaching normal weight. But these recommendations are changing with the availability of medications that are helping digestive function, but also are becoming linked with increased rates of overweight and obesity.

One of these is Vertex Pharmaceuticals’ Kaftrio, a CFTR modulator that helps the faulty CFTR channel protein fold correctly and keep it open longer. Kaftrio is sold as Trikafta in the U.S.

As life expectancy is increasing with Kaftrio and other therapies, concern is growing that patients will develop health issues associated with overweight or obesity.

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Effect of Kaftrio on weight changes in CF

While researchers often look at changes in BMI, this doesn’t offer information on body composition, the amount of fat, muscle, and bone a person has, leading two researchers in Wales to use a method called bioelectrical impedance to measure fat and fat-free mass in adults with CF before and after starting Kaftrio.

The study included 109 patients (76 men, 33 women) who were a mean age of 30.3. Nearly half (48%) carried two copies of the F508del mutation, the most common CF-causing mutation and a target of Kaftrio.

Almost all (90%) had pancreatic insufficiency, a digestive problem that occurs when the thick, sticky mucus associated with CF keeps food-digesting enzymes from entering the small intestine.

Body composition, BMI, lung function, and sweat chloride concentration — a measure often used to diagnose CF — were assessed at a median of five months before starting Kaftrio (range, 1-21 months) and at a median of seven months after treatment (range, 1-22 months).

Kaftrio led to a significant increase in mean forced expiratory volume in one second (FEV1%), a measure of lung function, from 67% to 75%. It also led to a significant decrease in mean sweat chloride concentration, indicating better CFTR protein function.

Patients also showed a significant increase in mean BMI, from 22.8 to 24.3, still within the healthy weight range. The number of men in the overweight and obese categories increased from 20 to 33 (27% to 44%), while women remained relatively stable, increasing from seven to eight (21% to 24%).

Body composition assessments showed patients’ fat mass increased by an average 2.1 kg (about 4.6 pounds), whereas fat-free mass increased by 2.5 kg (about 5.5 pounds). While these changes weren’t statistically significant, there was a significant increase in fat and fat-free mass indices, calculated based on weight and the percentage of either fat or fat-free mass.

The proportion of patients with normal weight obesity — a condition characterized by normal weight, but excess, or more than 30%, body fat — increased from 10% to 20%.

Men gained more fat-free mass than women, by a mean of 2.1 kg, but only the fat-free mass index showed a significant difference between them.

There was a greater increase in the number of women who had normal weight obesity compared with men (13% vs. 4%).

Regularly evaluating body composition may help identify people with too much fat mass, the findings suggest, allowing personalized care to optimize body composition.

“Routine FM and FFM assessment, potentially through the use of [bioelectrical impedance], may prove to be more useful markers of health indices than BMI alone in [people with CF] growing older,” the researchers said.