Metabolic

# NACFC2021 – Trikafta increases risk in CF patients with obesity disorders

Patients with cystic fibrosis (CF) who start Trikafta triple therapy may be at greater risk of problems related to being overweight or obese, such as:

“With the approval of triple therapy … weight gain and obesity are likely to become more noticeable, and therefore associated undesirable syndromes such as metabolic syndrome may appear,” said Gregory Ratti, MD, assistant professor at the University of Texas Southwestern. “We have to recognize these early in order to avoid long-term complications, as the life expectancy of our patients improves. “

Ratti spoke in the presentation at the North American Cystic Fibrosis Conference (NACFC) 2021: “Development of metabolic syndrome in a single center cohort after initiating treatment with elexacaftor-tezacaftor-ivacaftor. “

Trikafta from Vertex Pharmaceuticals is a triple combination therapy with CFTR modulators. It works by improving the functionality of the CFTR protein in people with specific CF-causing mutations.

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The data suggest that treatment with Trikafta may help CF patients gain weight. Since CF is a common cause of malnutrition, it is generally considered beneficial, but weight gain also carries risks.

According to a 2019 report by the CF Foundation, approximately 23.1% of the CF population were overweight and another 8.3% were obese. For comparison: in 1999, 12.8% of CF patients were overweight or obese.

“Obesity is becoming a much more important problem in our CF population,” said Ratti. “That’s why we have need to investigate the complications associated with this disorder. ”

Those complications include high blood pressure, or high blood pressure “which we traditionally have no problem with” in CF, Ratti said. However, the same 2019 report found that 6.4% of adults with CF had high blood pressure – a rate similar to osteoporosis (weak bones) or hemoptysis (coughing up blood), which traditionally receive much more attention in CF clinical practice.

Other obesity-related complications have also long been considered of little relevance to CF. Ratti noted that the questionnaire used in the CF Foundation’s report did not address cardiovascular problems such as hyperlipidemia (high levels of fat in the blood). Nonetheless, new research is drawing attention to the prevalence of these health problems in the CF population.

Metabolic syndrome is a constellation of five metabolic risks for type 2 diabetes and cardiovascular disease: obesity, high blood pressure and abnormal levels of fat, cholesterol and / or sugar in the blood. At least three of these five cardiovascular factors must be present in order to diagnose metabolic syndrome.

“Metabolic syndrome is very common,” Ratti said, noting that over a third of adults in the US are qualified for this diagnosis. It is well known that people with metabolic syndrome are at increased risk for heart, kidney, and liver disease.

At NACFC, Ratti presented data from 100 CF patients who started Trikafta between late 2019 and early 2021 and were available for at least one year of follow-up data.

Of these, 44 had never been treated with a CFTR modulator, while 48 had previously used Symdeko and eight had been treated with Orkambi, both of which are dual combination therapies with CFTR modulators.

Almost all of the patients were white; around half were female and their average age was around 30 years. Almost all of them had pancreatic insufficiency and about a third had CF-related diabetes (CFRD).

Of these 100 patients, five met the criteria for metabolic syndrome before starting treatment with Trikafta. After one year of therapy, this number had increased significantly to 16 patients. Statistical analyzes showed no difference in the risk of developing metabolic syndrome based on whether or not patients had received prior CFTR modulator therapy.

“One year after the start of the [Trikafta], there is a significant increase in the incidence of metabolic syndrome in our patient population, “said Ratti.

At the same time, the number of patients with high blood pressure rose from 11 to 21.

Increases, although not statistically significant, were also found in the patients’ average blood fat levels and in the average waist circumference (for assessing obesity). It is noteworthy that the number of patients with CFRD has not changed.

After one year of therapy, better lung function and weight gain were seen, although the variability in both results was high. Ratti noted significant weight gain in patients taking psychiatric drugs, for which weight gain is a known side effect.

Taken together, these results underscore the need to screen for metabolic syndrome in CF patients with trikafta, Ratti said, adding that his center tries to do such screening “at least once a year”.

Editor’s Note: The Cystic Fibrosis News Today team will be covering the virtual North American Cystic Fibrosis Conference (NACFC) 2021 November 2-5. Check out the latest stories from the conference here.

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