BMI increase with Kaftrio may not be linked to energy intake

Gains might be result of different energy requirements, metabolism

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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An increase in body mass index (BMI) in people with cystic fibrosis (CF) under Kaftrio therapy may not be attributable to increased energy intake, according to a new U.K. study.

Instead, gains in BMI, a measure of body fat, might reflect other factors, such as different energy requirements and metabolism, according to the researchers.

The study, “Body mass index and nutritional intake following Elexacaftor/Tezacaftor/Ivacaftor modulator therapy in adults with cystic fibrosis,” was published in the Journal of Cystic Fibrosis.

CF is caused by mutations in the CFTR gene, leading to defects in the production or function of the CFTR protein. This causes the accumulation of unusually thick and sticky mucus, particularly in the lungs and digestive tract, causing tissue damage.

Kaftrio (Trikafta in the U.S.) is a triple combination CFTR modulator — elexacaftor, tezacaftor, and ivacaftor — designed to help defective CFTR proteins work more effectively. It’s been shown to increase patients’ weight — thought to be a reflection of increased appetite and nutritional intake — as well as greater clinical stability. “However, no study has directly investigated this to date,” wrote the researchers,  who assessed 50 adults with CF (53% men) enrolled in the Igloo-CF study, an observational study conducted across four CF care centers in the U.K.

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Changes ini BMI, energy intake with Kaftrio

Of them, 40 were analyzed before and after the Kaftrio therapy was introduced, with a follow-up that lasted a median of 68 weeks (about 1.3 years). The median duration of treatment was 23 weeks.

Another 10 patients weren’t on Kaftrio. Mean follow-up duration in this group was 28 weeks.

No significant differences were observed between the two groups regarding BMI and lung function, assessed by forced expiratory volume in one second — the maximum amount of air a person can exhale in one second — at the start of the study (baseline) or follow-up.

With Kaftrio, the median BMI increased significantly from 23.03 kg per square meter (kg/m2) at baseline to 24.58 kg/m2 at follow-up. In contrast, energy intake significantly decreased from 2,551 to 2,153 kcal/day. As expected, lung function improved significantly at follow-up.

The contribution of macronutrients — proteins, fat, and carbohydrates — to total energy intake didn’t change significantly between baseline and follow-up. “This suggests an overall reduction in intake rather than one macronutrient being greatly altered,” the researchers wrote.

Fiber intake at follow-up was half of what’s recommended for the general population of 30 g/day.

“As life expectancy increases, the lack of dietary fiber may potentially accentuate gut dysbiosis [imbalance of gut microbial community], cardiovascular disease, and colorectal cancer risk,” the researchers added.

Patients on double CFTR modulator therapy before Kaftrio (either Orkambi or Symkevi, Symdeko in the U.S.), which accounted for 15 participants, had a lower median BMI and higher energy intake at baseline than those on no modulator therapy.

At follow-up, both groups increased their BMI and decreased energy intake, but the differences were only significant for those on no modulator at baseline.

The percentage change of either BMI or energy intake didn’t correlate with the number of weeks on Kaftrio. The data also showed that, in patients not on Kaftrio, the median BMI and energy intake didn’t differ between the start and follow-up.

“It could be speculated that the weight gain following [Kaftrio] therapy may not be simply attributable to increased energy intake, but may reflect a host of other factors, such as altered energy requirements and metabolic perturbations,” the scientists said. “Further exploration into the underlying [causes] of weight gain with ETI therapy is needed.”