(208) Fat soluble vitamin level trends post-elexacaftor/tezacaftor/ivacaftor therapy

Background: An estimated 85% of cystic fibrosis patients are pancreatic insufficient, and are at risk for fat malabsorption and thus fat soluble vitamin deficiency. CFTR modulators have not only improved respiratory function, but also nutritional markers. A small study of pediatric patients receiving lumacaftor/ivacaftor for two years showed a significant increase in Vitamin A (serum retinol) levels, a significant decrease in Vitamin E, and a non-significant change in Vitamin D (25-OH-cholecalciferol) levels. A recent study reported that median Vitamin D levels increased by 5 ng/mL one year after elexacaftor/tezacaftor/ivacaftor therapy. Of more concern, three case reports of hypervitaminosis A resulting in papilledema after initiation of elexacaftor/tezacaftor/ivacaftor have recently been reported. The long-term impact of highly effective modulators on fat soluble vitamin levels is unknown.

Methods: In this study, changes in fat soluble vitamin levels before and after elexacaftor/tezacaftor/ivacaftor initiation was assessed. Adult and pediatric CF patients who were prescribed elexacaftor/tezacaftor/ivacaftor were included. Patients who received a solid organ transplant were excluded. Vitamin A, D, and E levels prior to therapy initiation and all post-therapy levels through February 2022 were collected. Descriptive statistics were used. Comparative statistics will be completed.

Results: A total of 366 patients were included (53% female); 93 patients were pediatric aged at the time of therapy initiation. 219 patients were homozygous F508del, and 150 patients were modulator naïve prior to initiation of elexacaftor/tezacaftor/ivacaftor. As seen in Table 1, there was an increase in Vitamin A over time with no instances of hypervitaminosis A (defined as greater than 120 mcg/dL per the World Health Organization). As an aggregate, Vitamin D levels both increased and decreased over time. In the pediatric cohort, there was a decrease in Vitamin D at all time points. Six adult patients had Vitamin D levels of greater than 80 ng/mL at least once; all but two patients had a repeat level in the study time frame, with two remaining greater than 80 and the other two decreased significantly to 27.9 and 32.2 ng/mL. Vitamin E levels remained relatively unchanged through 24 months post-therapy. However, at greater than 24 months post-initiation, Vitamin E levels increased, although the number of patients with levels drawn at that time was low.

Conclusions: Highly effective modulator therapy may increase the absorption of some fat soluble vitamin levels. From a safety perspective, the vast majority of levels remained below toxic thresholds. Additional investigation and guidance is needed to determine if fat soluble vitamin supplementation strategies need to be modified post initiation of a highly effective modulator.

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