Efficacy and safety of long-term treatment with monthly calcifediol soft capsules in vitamin D deficient patients

Abstract

Background

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions (such as immunomodulation). In this sense, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, its optimal dosing and treatment duration, despite being the direct precursor of calcitriol and the biomarker of vitamin D status.

Objectives

To assess the efficacy and safety of long-term treatment with calcifediol soft capsules compared to cholecalciferol (vitamin D3) in vitamin D deficiency.

Methods

This was a Phase III-IV, double blind, randomised, controlled, multicentre clinical trial. Postmenopausal women with baseline levels of 25(OH)D < 20 ng/ml were randomised 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25 000 IU/month for 12 months.

Results

303 patients were enrolled, and 298 were included in the ITT population. There were no significant differences in terms of demographic variables, and the mean basal 25(OH)D levels were 13.2 ± 3.7 ng/ml. After 4 months of treatment, 25(OH)D levels over 30 ng/ml were reached by 4.3 times more patients in calcifediol group than in cholecalciferol group. The superiority of calcifediol over cholecalciferol in terms of increasing 25(OH)D levels was shown throughout the 12 months. However, the biggest difference was observed after the first month of treatment (mean change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in both calcifediol groups combined and in cholecalciferol group, respectively). After month 4, the increase in 25(OH)D levels remained fairly stable during the next 8 months of treatment. However, those patients in the group of calcifediol + placebo, despite having mean 25(OH)D levels of 28.5 ng/ml at month 4, went back to basal levels after withdrawal of treatment (16.1 ± 6.0 ng/ml at month 8 and 14.4 ± 6.0 ng/ml at month 12). Regarding safety, no patient reached 25(OH)D toxic levels (> 100 ng/ml), with 64.4 ng/ml being the highest concentration reported during the study. No relevant treatment-related safety issues were reported in any of the groups studied.

Conclusion

Calcifediol is efficient, faster and more potent than cholecalciferol in raising 25(OH)D levels. After 4 months of treatment, calcifediol 0.266 mg/month reaches its maximum efficacy within safe 25(OH)D levels, remaining fairly stable when treatment continues. Discontinuation of calcifediol supplementation lowers 25(OH)D levels back to baseline, suggesting that long-term treatment is safe and necessary.