Levels of vitamin A increase a year into Kaftrio treatment: Study

Pancreatic insufficiency, inflammation contribute to poor absorption

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Levels of fat-soluble vitamins D and E and of the micronutrients zinc and selenium are generally within the normal range in people with cystic fibrosis (CF), even during treatment with Kaftrio.

That’s according to a recent study that also found significantly increased vitamin A levels one year into treatment, compared with before therapy.

“This study adds to the evidence that improvements of some fat-soluble vitamin levels can be found after [Kaftrio],” the researchers wrote in “Changes in vitamins and trace elements after initiation of highly effective CFTR modulator therapy in children and adults with cystic fibrosis – a real-life insight,” which was published in Molecular and Cellular Pediatrics. “Individualized follow-up and supplementation are recommended,” they said.

CF is caused by mutations in the CFTR gene that lead to an abnormally thick and sticky mucus being produced that accumulates in the lungs, pancreas, digestive tract, and other organs.

In CF, both pancreatic insufficiency and intestinal inflammation have been reported to reduce the absorption of fat, fat-soluble vitamins (vitamins A, D, E, and K), and micronutrients, that is, vitamins and minerals needed by the body in very small amounts, such as zinc or selenium. Fat-soluble vitamins can dissolve in fats and oils.

Treatment with CFTR modulators improves the uptake of fat-soluble vitamins and micronutrients, but the effects of changes in fat-soluble vitamins and micronutrient levels after Kaftrio is started aren’t fully known, leading researchers at the Ulm University Medical Center, Germany to analyze their levels in children and adults with CF. Kaftrio, a highly effective CFTR modulator meant to increase CFTR function, is a triple combination therapy of elexacaftor, tezacaftor, and ivacaftor that’s sold as Trikafta in the U.S.

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Changes with Kaftrio treatment

All the participants had at least one copy of the F508del mutation, the most common CF-causing mutation. A total of 58 patients (14 children, 44 adults) who started Kaftrio at the researchers’ center between August 2021 and March 2022 were included. The patients’ age ranged between 7-59 (median, 28), and they were followed at least a year.

One year after starting Kaftrio, patients’ FEV-1, that is, the forced expiratory volume in one second, a measure of lung function, increased significantly from a mean of 2.3 L (64% of FEV1 predicted) before treatment to 2.69 L (75.6% of FEV1 predicted). Children and adults didn’t differ in their scores.

Sweat chloride levels, which are abnormally high in CF, were also significantly decreased between three and nine months after starting treatment. Levels at one year also were lower than before, though the difference wasn’t statistically significant.

Also, after a year, aspartate aminotransferase remained unchanged, But alanine aminotransferase, another liver damage marker, were significantly increased four weeks into Kaftrio, but decreased thereafter. Bilirubin, a product of the breakdown of red blood cells that also indicate liver problems remained elevated throughout the follow-up. One patient was diagnosed with Gilbert’s syndrome, a liver condition, due to persistently high bilirubin and two others were suspected of having Gilbert’s syndrome.

“Interestingly, total bilirubin was permanently elevated after [Kaftrio], but most patients still showed bilirubin values within the reference range,” the scientists wrote. “Increases of transaminases and bilirubin are well-known side effects of [Kaftrio] therapy and only temporary in nature in most cases.”

According to the researchers, “close monitoring of liver function tests is warranted, with some changes occurring rapidly and others more in the long term.”

Levels of fat-soluble vitamins and of the trace elements zinc and selenium were generally normal. Only vitamin A was significantly elevated a year after Kaftrio. The therapy was well tolerated. Four patients needed to interrupt treatment temporarily due to elevated levels of liver damage markers, but tolerated it well afterwards.

“It seems sensible to appreciate vitamin levels regularly after initiation of [Kaftrio]. Vitamin supplementation needs to be continued, but individual compositions of vitamins and trace elements might be reasonable for personalized CF therapy,” wrote the researchers, who said advised follow-up “after four weeks, three, six, nine and 12 months of the start of [treatment] and at least yearly afterwards” to help identify the few patients who do “require a change in supplementation.”