Blood fats rise with Trikafta, but no direct link to weight gain seen
Study into body mass index, fat and vitamin level changes with treatment
No significant link was seen between an increase in body mass index (BMI), a measure of body fat based on weight and height, and higher blood fats and vitamin levels in people with cystic fibrosis (CF) being treated with Trikafta (elexacaftor/tezacaftor/ivacaftor), a study in adult and pediatric patients reported.
While concerns of excessive weight or obesity among patients using an effective CFTR modulator therapy like Trikafta are growing, “there was not a significant association between the degree of weight gain and change in nutritional markers, as we had hypothesized,” its researchers wrote. They urged further study into modulator use and the risks of obesity.
The study, “Impact of elexacaftor/tezacaftor/ivacaftor on lipid and fat-soluble vitamin levels and association with body mass index,” was published in Pediatric Pulmonology by scientists at Case Western Reserve University School of Medicine in Ohio.
Trikafta is a triple-combination modulator therapy for cystic fibrosis
Trikafta (known as Kaftrio in Europe), sold by Vertex Pharmaceuticals, works to improve lung function in children and adults who have at least one copy of F508del or another CF-causing mutation that’s responsive to the treatment.
Besides disease symptoms affecting the lungs, CF historically has caused poor growth and difficulty putting on weight. Trikafta is known to improve patients’ nutritional status and to help with weight gain, particularly among those who are underweight before its use.
To better understand Trikafta’s effects on certain fats and fat-soluble vitamins, the researchers reviewed blood tests from 110 adults (average age, 30) and 26 adolescents (average age, 15) before and a median of about six months (181 days) after beginning treatment. All carried at least one copy of F508del and were being followed at a Cleveland CF center.
As expected, Trikafta significantly improved their lung function, as measured by an increase in the percent predicted forced expiratory volume in one second — the amount of air that can be quickly and forcefully exhaled — from a median 66.1% to 77.3%.
Likewise, median BMI rose significantly in adults (from 21.9 to 23.5 kilograms per square meter) and adolescents (from 48% to 63%, expressed as a percentile that takes into account age and sex).
Increases seen with treatment in blood cholesterol and vitamin A and D levels
Total cholesterol, a fat-like molecule that’s found in all cells, increased from a median 126 to 154 milligrams per deciliter (mg/dL). Low-density lipoprotein, also known as bad cholesterol, rose from 63 to 78 mg/dL, while high-density lipoprotein or good cholesterol increased from 43 to 49 mg/dL with treatment.
Higher median levels were recorded for vitamin D (34.5 vs. 38 nanograms per milliliter) and vitamin A (40.1 vs. 47.9 micrograms per deciliter), whereas those of vitamin E did not change significantly (9.2 vs. 9.6 micrograms per milliliter).
“These results add to the existing literature suggesting highly effective CFTR modulator therapy is associated with changes in lipid [fat] and fat-soluble vitamin levels,” the researchers wrote.
Despite an increase in fats and vitamins in the bloodstream, no significant link was evident between changes in BMI and changes in blood fats or vitamin levels in these adult and adolescent patients.
“The degree of change in BMI did not correlate significantly with the change in lipid or vitamin levels in adults, nor did the degree of change in BMI correlate significantly with the change in vitamin levels in the pediatric population with CF,” the researchers reported, adding that the duration of Trikafta’s use also did not significantly associate with changes in these levels.
“Although higher BMI has historically been associated with improved survival in [people with] CF, the possibility of adverse consequences from obesity in CF is a growing concern,” they added. “Further prospective research is needed to understand the impact of highly effective modulator therapy on risks associated with obesity, including cardiovascular risk.”