#NACFC2022 – Trikafta Use Tied to CF Body Weight, Cholesterol Gains

Approved CF therapy also linked to increases in 'bad' cholesterol

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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An illustration shows images of lungs flanking an announcement of the North American Cystic Fibrosis Conference.

Treatment with Trikafta leads to an increase in body weight and cholesterol levels among people with cystic fibrosis (CF), according to a new study into the impacts of the approved CF triple therapy.

The study found gains in body mass index — BMI, a measure of body weight — and both “good” and “bad” cholesterol for CF patients on Trikafta (elexacaftor/tezacaftor/ivacaftor).

Krithika Sundaram, a medical student at Northeast Ohio Medical University, shared the findings at the 2022 North American Cystic Fibrosis Conference, held Nov. 3–5 in Philadelphia. The talk was titled “Impact of cystic fibrosis transmembrane conductance regulator(CFTR) modulator therapy on nutritional status, hepatic steatosis, and dyslipidemia.”

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Investigating therapy’s impact on nutrition status

Cystic fibrosis is caused by mutations that impair the functionality of the CFTR protein, which helps to control the movement of water and salt molecules in and out of a cell. CFTR modulators are a class of therapies that can improve the functionality of this protein in people with specific CF-causing mutations.

While CF is commonly characterized by lung problems, the disease also usually affects other parts of the body. For example, many people with CF have digestion problems that limit their ability to get nutrients from the food they eat.

CFTR modulator treatments, whose benefits in lung function are well-known from clinical trials, have been shown to increase both body weight and body mass index — a ratio of weight to height — in CF patients. In fact, median BMI values for CF patients have been steadily increasing in the last two decades. Also, an increase in cholesterol has been reported in patients with CF-related diabetes.

Now, researchers sought to assess the impact of CFTR modulators on levels of fat molecules and also on hepatic steatosis — fatty liver disease, previously shown to be associated with higher BMI in people with CF.

To that end, 30 adults with CF underwent an abdominal MRI under no modulator treatment, under the highly effective Trikafta therapy, or under the combination treatments Orkambi (ivacaftor/lumacaftor) or Symdeko (tezacaftor/ivacaftor).

Eight patients had data available from before or after starting on Trikafta. Median BMI increased significantly with Trikafta, from 22.7 to 24.7 kilograms per square meter (kg/m2).

Median levels of low-density lipoprotein cholesterol (LDL-C), sometimes called “bad” cholesterol, increased from 73 to 90 mg/dL after a year on Trikafta. Median levels of so-called “good” cholesterol, high-density lipoprotein cholesterol (HDL-C), also increased significantly, from 48 to 52 mg/dL.

Significant improvements in lung function were also noted.

Levels of fat molecules called triglycerides in the blood and measures of fat in the liver did not change significantly following Trikafta treatment.

“Treatment with the highly effective CFTR modulator [Trikafta] was associated with an increase in [lung function], BMI, HDL-C, and LDL-C,” Sundaram said.

Eight patients had data comparing no modulator with any modulator therapy. Median BMI increased significantly from 21.8 to 24.7 kg/m2. Levels of cholesterol molecules and triglycerides did not change significantly in these patients. No significant changes were seen in lung function or hepatic steatosis measures.

In conclusion, Sundaram noted that it is “important to monitor cardiometabolic risk factors in CF patients on modulator treatment.”

Such monitoring can help to assess the potential impact of Trikafta and other therapies, the researchers noted.

The team stressed that this analysis is limited by the small number of patients involved and by the fact that not all participants were getting regular fat molecules assessments.

Note: The Cystic Fibrosis News Today team is providing in-depth coverage of the 2022 North American Cystic Fibrosis Conference (NACFC) Nov. 3-5. Go here to see the latest stories from the conference.

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