Levels of vitamins D, A increase with Kaftrio, study finds
Researchers say findings may warrant review of supplement recommendations
Children and adolescents with cystic fibrosis (CF) treated with Kaftrio, marketed as Trikafta in the U.S., experienced increases in the fat-soluble vitamins D and A for up to one year, according to a study from Spain.
Treatment reduced the proportion of participants with vitamin D and vitamin A deficiency, the study found. But the vitamin A increase seen at six months in participants treated with Orkambi (ivacaftor/lumacaftor) or Symkevi (tezacaftor/ivacaftor) was not maintained at one year.
“Further studies are needed to confirm these findings,” and if future studies show similar results, “a review of current vitamin supplementation recommendations for patients treated with [Kaftrio], particularly regarding potential toxicities,” may be necessary, the researchers wrote.
The study, “Effect of cystic fibrosis modulator therapies on serum levels of fat-soluble vitamins,” was published in the Journal of Pediatric Gastroenterology and Nutrition.
CF is caused by mutations in the CFTR gene that result in missing or dysfunctional CFTR protein. This leads to the accumulation of thick and sticky mucus in several organs, including the lungs, pancreas, and the digestive tract.
Vitamin deficiencies in CF
People with CF may experience deficiencies in fat-soluble vitamins. Exocrine pancreatic insufficiency (EPI), a common CF symptom, is characterized by the insufficient release of pancreatic enzymes needed to break down nutrients.
Treatment with CFTR modulators has been shown to improve patients’ nutritional status through different mechanisms, one of them being better fat absorption. “Therefore, it would be expected that fat-soluble vitamin levels would improve with [CFTR modulators],” the scientists wrote.
To know more, they analyzed children and adolescents from 14 CF Spanish centers who were candidates to start CFTR modulator treatment at the study’s start. A total of 224 participants, ranging in age from 11.4 to 16.3 and carrying at least one copy of the F508del mutation (the most common cause of CF), were included in the study.
Overall, 173 patients were treated with Kaftrio (elexacaftor/tezacaftor/ivacaftor) while 51 received one of two dual therapies: Orkambi or Symkevi, sold as Symdeko in the U.S.
Participants on dual therapies were significantly younger (mean age 10.8 vs. 14), and less commonly had Pseudomonas aeruginosa infections in thee airways (9.8% vs. 22.5%) than those treated with Kaftrio.
Results showed a significant increase in blood levels of vitamin D and vitamin A after six months and 12 months of treatment. The group treated with Kaftrio experienced significant increases in both vitamins’ levels within the first six months, which were maintained after one year.
However, with dual therapies, only vitamin A levels increased within the first six months, and the effect was not maintained at 12 months.
In the Kaftrio group, the proportion of patients with insufficient vitamin D levels (lower than 30 nanograms/mL) decreased from baseline to six months (64% vs. 45%) and 12 months (61% vs. 48%). A similar trend was seen in the proportion of those with vitamin D deficiency (lower than 20 nanograms/mL) from baseline to six months (23% vs. 10%) and from baseline to 12 months (28% vs. 15%).
“Patients treated with [Kaftrio] showed early improvement in vitamin D levels, which was sustained over time,” the researchers wrote. “If these results are confirmed, the recommendations for vitamin D supplementation may need to be revised.”
A similar effect was seen when looking at vitamin A deficiency in the group on Kaftrio, as the proportion of children and adolescents with vitamin A deficiency (lower than 30 mcg/dL) decreased significantly at six months (6% vs. 21%). Kaftrio treatment also increased the proportion of patients reaching an increase of vitamin A to toxic levels after six months (3% vs. 11%).
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