In people with cystic fibrosis (CF), levels of the fat-soluble vitamins D and E and the micronutrients zinc and selenium are usually within normal ranges, even during treatment with Kaftrio.
This is according to a recent study, which also found that vitamin A levels were significantly higher one year after starting treatment compared to before treatment.
“This study shows that levels of some fat-soluble vitamins [Kaftrio]The researchers said:Vitamin and trace element changes following initiation of highly effective CFTR modulating therapy in children and adults with cystic fibrosis – practical insights“teeth, Molecular and Cellular Pediatrics“Individual follow-up and supplementation are recommended,” the researchers said.
CF is CFTR This gene causes abnormally thick, sticky mucus to be produced and accumulate 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 fats, fat-soluble vitamins (vitamins A, D, E, and K), and micronutrients (vitamins and minerals that the body needs in very small amounts, such as zinc and selenium). Fat-soluble vitamins dissolve in fats and oils.
Treatment with CFTR modulators improves the absorption of fat-soluble vitamins and micronutrients, but the impact of changes in fat-soluble vitamin and micronutrient levels after starting Kaftrio is not fully understood, so researchers at the University Medical Center of Ulm in Germany are analyzing their levels in children and adults with CF. Kaftrio, a highly effective CFTR modulator aimed at boosting CFTR function, is a triple combination therapy of elexacaftar, tezacaftar and ivacaftar, sold in the United States as Trikafta.
Changes after Kaftorio treatment
All participants had at least one copy of the F508del mutation, the most common mutation that causes CF. A total of 58 patients (14 children and 44 adults) who started receiving Kaftrio at the researchers’ centers between August 2021 and March 2022 were included. Patients ranged in age from 7 to 59 years (median 28 years) and were followed for at least one year.
One year after starting Kaftorio, patients’ FEV-1 (forced expiratory volume in 1 second, an index of lung function) increased significantly from a pre-treatment mean of 2.3 L (64% of predicted FEV1) to 2.69 L (75.6% of predicted FEV1). There was no difference between scores in children and adults.
Sweat chloride concentrations, which are abnormally high in CF, also decreased significantly between 3 and 9 months after treatment began. Levels were also lower after 1 year than before treatment, but the difference was not statistically significant.
After one year, aspartate aminotransferase levels were unchanged, but alanine aminotransferase, another marker of liver damage, increased significantly during the first four weeks of treatment but then declined. Bilirubin, a product of red blood cell breakdown that indicates liver problems, remained elevated throughout the follow-up period. One patient was diagnosed with Gilbert’s syndrome, a liver disease, because of persistently high bilirubin levels, and the other two were suspected of having Gilbert’s syndrome.
“Interestingly, total bilirubin levels [Kaftrio]”However, most patients still had bilirubin values within the reference range,” the scientists wrote. “Elevations in transaminases and bilirubin were [Kaftrio] In most cases, it is only a temporary fix.”
“Close monitoring of liver function tests is warranted, as some changes occur rapidly and others over the longer term,” the researchers said.
Concentrations of fat-soluble vitamins and the trace elements zinc and selenium were generally normal. After 1 year of Kaftorio, only vitamin A was significantly elevated. The treatment was well tolerated. Four patients had to temporarily discontinue treatment due to elevated concentrations of liver damage markers, but it was well tolerated thereafter.
“Once initiated, it seems reasonable to assess vitamin levels periodically. [Kaftrio]”Vitamin supplementation should be continued, but a tailored combination of vitamins and trace elements may be reasonable for individualized treatment of CF,” the researchers wrote, recommending follow-up visits 4 weeks and 3, 6, 9, and 12 months after treatment initiation. [treatment] They recommended that the supplement be discontinued “at least annually thereafter” to identify the small number of patients “in need of a change in supplement.”
