Trikafta May Improve Vitamin D Absorption in CF Patients
One year of Trikafta treatment increases the blood levels of vitamin D in people with cystic fibrosis (CF) who are on vitamin D supplements.
These early findings from a small study suggest that the therapy may improve vitamin D supplement absorption, and that vitamin D levels should be frequently monitored to determine whether supplement dosing may be reduced.
More studies are needed to assess the clinical impact of improved vitamin D absorption in this patient population, the researchers noted.
Results of the study, “Impact of elexacaftor/tezacaftor/ivacaftor on vitamin D absorption in cystic fibrosis patients,” were published in the journal Pediatric Pulmonology.
Besides lung function impairment, CF also commonly causes exocrine pancreatic insufficiency, in which the pancreas is unable to release digestive enzymes to break down food in the intestines.
As such, CF patients “are at risk for fat-soluble vitamin deficiencies,” the researchers wrote, adding that most of those with pancreatic insufficiency “take a CF-specific multivitamin containing extra vitamin A, D, E, and K,” that, when insufficient, can be complemented with additional individual supplements.
Vitamin D deficiency is common in CF patients and can lead to osteoporosis, in which bones become fragile and are more likely to break. This deficiency usually is managed with vitamin D supplements, such as cholecalciferol, or vitamin D3.
Vertex Pharmaceuticals’ Trikafta is a combination of three oral medications (elexacaftor, tezacaftor, and ivacaftor) that work to increase the functionality of the CFTR protein, which is impaired in people with CF. This CFTR modulator therapy is approved for CF patients with specific disease-causing mutations in CFTR, the gene that provides instructions for making the CFTR protein.
Notably, previous studies suggested that ivacaftor has the potential to restore pancreatic enzyme secretion, and thereby nutrient absorption.
Now, a team of researchers at University of Iowa Hospitals and Clinics evaluated whether Trikafta improved vitamin D absorption by retrospectively analyzing the data from 76 CF patients (50 males and 26 females) followed at the University of Iowa’s Cystic Fibrosis Center from Oct. 21, 2018 until Feb. 28, 2021.
Analyzed data included blood levels of 25-hydroxyvitamin D — the major form of vitamin D in the blood — before Trikafta and after one year of treatment, pancreatic insufficiency status, current multivitamin and/or cholecalciferol supplementation, and history of other CFTR modulators.
Patients’ mean age was 25.8 years, most of them carried F508del mutations (59.2%) — the most common CF-causing mutation — in both CFTR gene copies, and were pancreatic insufficient (94.7%). More than two-thirds (68.4%) had been treated previously with other CFTR modulators, most often Orkambi (lumacaftor/ivacaftor) and Symdeko (tezacaftor/ivacaftor).
They received a mean of 1,570 micrograms of cholecalciferol per week before Trikafta, and throughout the study, 19 (25%) patients experienced changes in their maintenance cholecalciferol dose due to “variations in adherence, formulation, or access to vitamins,” the researchers wrote.
Results showed that before Trikafta, patients’ median vitamin D levels were 27.5 nanograms per milliliter (ng/mL) — below the minimum normal of 30 ng/mL. After starting on Trikafta treatment, these levels were increased significantly by a median of 5 ng/mL.
Notably, a less-pronounced vitamin D increase of 2 ng/mL was observed among the 19 patients with changes in maintenance cholecalciferol dose during the study, while patients who did not have a dosage change saw their levels rise by a median of 5 ng/mL.
These findings indicate that Trikafta treatment increases vitamin D levels in the blood, which may be due to “changes in pancreatic absorption or vitamin D processing and utilization within the body,” the team wrote.
As such, vitamin D levels should be monitored more frequently in CF patients initiating Trikafta “to determine if supplement dose modification is warranted,” the scientists wrote, adding that increases in vitamin D levels may “warrant reductions in total weekly doses of cholecalciferol and/or multivitamin products.”
Of note, higher-than-normal levels of vitamin D can lead to abnormally high blood calcium levels, which can cause nausea and vomiting, weakness, and frequent urination.
In addition, since vitamin D has been hypothesized to improve not only bone health, but also lung function in people with CF, further studies are needed to assess the impact of these level changes in terms of clinical outcomes.
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