Cystic fibrosis therapies changing landscape of nutrition, cardiometabolic health

The use of triple therapy and other highly effective modulator therapies will likely change the landscape of nutrition and that of cardiometabolic parameters in patients with cystic fibrosis, a speaker said.

At the North American Cystic Fibrosis Conference, Marina Litvin, MD, associate professor of medicine at the Washington University School of Medicine, St. Louis, discussed the “changing parameters” in nutritional status of patients with cystic fibrosis and the emergence of overnutrition and obesity, as well as the effects of highly effective modulator therapy on cardiovascular parameters.

Data from the Cystic Fibrosis Foundation Patient Registry Annual Data Report 2019 highlighted an increase in BMI and weight among children and adults with cystic fibrosis from 1999 to 2019. According to Litvin, “this is likely due to our effective multidisciplinary approach, better nutrition [and] earlier diagnosis, but it is also reflecting what is happening in the population as a whole ... especially in areas of Western diets where overall the overweight and obesity incidence is increasing as well.” Litvin said this is important because among patients with a BMI of 25 kg/m² or greater, there is a significant increase in the risk for adverse outcomes, with mortality increasing 30% every 5 BMI units above normal, and mortality due to chronic kidney disease and type 2 diabetes increasing 60% and 120%, respectively.

Highly effective modulator therapy with elexacaftor/tezacaftor/ivacaftor (Trikafta, Vertex Pharmaceuticals) was approved by the FDA for treatment of cystic fibrosis in October 2019. The triple therapy improves the processing and trafficking of the CFTR protein and was shown in clinical trials that, in addition to improving lung function, there was a decrease in sweat chloride and an increase in weight, Litvin said, which was also seen with other medications that target CFTR such as ivacaftor (Kalydeco, Vertex Pharmaceuticals) and lumacaftor.

This medication should be taken in conjunction with high fat foods, which may cause an increase in caloric intake. In addition, this therapy may cause decreases in energy expenditure and can improve a patient’s sense of taste, smell, absorption and appetite, which can all result in higher caloric intake and overall weight gain, according to Litvin.

Litvin and colleagues conducted a single-center, retrospective, observational analysis of the effect of elexacaftor/tezacaftor/ivacaftor on body weight and cardiometabolic parameters in 134 adults with cystic fibrosis from the Washington University Adult Cystic Fibrosis Center. They assessed body weight, BMI, lipid profiles and blood pressure in outpatients 1 year before they initiated elexacaftor/tezacaftor/ivacaftor and again at a median of 12.2 months after treatment. Researchers observed significant weight increases, with fewer patients who were underweight or normal weight and significantly more patients who were overweight or obese 1 year after elexacaftor/tezacaftor/ivacaftor initiation, Litvin said. The researchers also observed a decrease in the number of patients with normal BP prior to treatment compared with on treatment. This may be due to the effect of elexacaftor/tezacaftor/ivacaftor on sodium chloride secretion, therefore, causing more water retention, which can increase BP and weight, Litvin said.

Also, while on elexacaftor/tezacaftor/ivacaftor, patients without cystic fibrosis-related diabetes had significant improvement in their blood glucose levels, but patients with cystic fibrosis-related diabetes showed no change in blood glucose, but did have increases in cholesterol.

The potential mechanisms for changes in glycemic and lipid parameters include increased caloric intake, improved absorption, improved exocrine pancreatic function, enhanced insulin secretion, increased weight and decreased inflammation, Litvin said.

“In addition to increase in overnutrition, and likely increase in incidence of hyperlipidemia and hypertension, our patients are living longer, and that fact within itself may place them at higher risk for cardiometabolic conditions, as well as coronary artery disease and stroke,” Litvin said.

Litvin offered the following recommendations for clinicians caring for patients with cystic fibrosis who are on highly effective modulator therapy:

• Assess weight, BMI and BP at each visit.
• Provide individualized counseling for each patient on caloric goals, fitness goals and nutritional status to aim for normal BMI.
• If a patient has abnormal BP, have the patient monitor BP at home in case this becomes a pattern wherein medical therapy may be considered.
• Continue annual oral glucose tolerance testing.
• Screen patients for hyperlipidemia development once a year.

"Patients would benefit from nutritional support services to identify and treat patients whose weight is not in a reasonable range,” Litvin said.

Future research is needed to establish how these factors contribute to increased risk for cardiovascular and cerebrovascular disease as well as mortality, Litvin said.