Study: Underweight CF patients see biggest weight gains with Trikafta

Overweight patients, those with less impaired CFTR function gained less weight

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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People with cystic fibrosis (CF) who were underweight before treatment gained the most weight after six months on Trikafta (elexacaftor/tezacaftor/ivacaftor), according to a new study.

Underweight participants, as assessed with the body mass index (BMI), also saw the biggest gains in treatment-related lung function. Patients who were overweight when starting the therapy and those carrying a residual function mutation with less impaired CFTR function gained less weight.

“We found that baseline BMI is the main determinant of [variability] in treatment response, with greater improvements observed in the population with lower BMI at [Trikafta] initiation,” wrote researchers in “Heterogeneity of weight gain after initiation of Elexacaftor/Tezacaftor/Ivacaftor in people with cystic fibrosis,” which was published in Respiratory Research.

Trikafta is a CFTR modulator therapy that treats the underlying cause of CF by correcting the defects in the CFTR protein’s production and function. Along with boosting lung function, it’s improved nutritional status, as indicated by an increase in BMI, a common measure of body fat content.

Still, “the response to [Trikafta] varied significantly and factors potentially related to BMI response have not yet been studied,” wrote the researchers in Italy, who enrolled 92 CF patients (60 males), ages 25-57, in the study to investigate the source of BMI variability with Trikafta. They collected data on factors that influence BMI response before treatment (baseline) and one and six months after starting.

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Variations in changes of body weight for CF patients with Trikafta

Among the participants, 64 (69.6%) were pancreatic insufficient and 59 (64.1%) had chronic respiratory infections caused by Pseudomonas aeruginosa. Lung function was severely impaired in 25 (27.8%), 10 (10.9%) were considered underweight (BMI less than 18.5 kg per square meters, kg/m2), and 10 were overweight (BMI of 25.0 kg/m2 or more).

During treatment, the participants’ average body weight increased by 1.6 kg (3.5 pounds) after one month and 3.1 kg (6.8 pounds) after six months. The average BMI increased by 0.57 kg/m2 at one month and 1.07 kg/m2 at six months.

Changes in body weight varied significantly with treatment, however. After six months, body weight ranged from a decrease of 4 kg (8.8 pounds) to an increase of 13.2 kg (29.1 pounds). BMI values also varied widely. Moreover, 13 (14.1%) patients showed no body weight increases.

Better treatment responses, in both weight and BMI, were associated with a lower BMI before treatment. After six months, underweight patients gained an average of 4.6 kg (10.1 pounds), while those of normal weight gained 3.2 kg (7 pounds). Overweight participants gained 0.7 kg (1.5 pounds).

Similar trends were seen with BMI values. About 14% of the variability was explained by baseline BMI.

Less weight gain was also seen with a CFTR residual function mutation (1.7 vs. 3.2 kg) where the CFTR protein is not as impaired. In these patients, the onset of CF is delayed and progresses slower than the more common forms. Here, a residual function mutation represented about 9% of the variability.

Most underweight patients (80%) moved into the normal weight category after six months, while a few normal-weight patients (15.3%) became overweight.

BMI changes moderately correlated with improved lung function as measured by a mean 14.5% increase in the percent forced expiratory volume (ppFEV1), a standard measure of how much air can be expelled. Lung function was better across all BMI categories, with underweight patients having the best gain of 24.5% ppFEV1.

“Baseline BMI is the major determinant of heterogeneity in weight gain in patients with CF treated with [Trikafta], with patients affected by underweight receiving the greatest benefit from this treatment,” the researchers said, noting excess weight in patients on Trikafta should be monitored.