https://smjournals.com/nephrology-kidne-diseases/fulltext/smjnkd-v2-1015.pdf
Patients were randomized to two different study groups: A and B. The total study duration was 52 weeks long. Each study group was randomized in a 2:1 ratio to receive either 30 mcg ER calcifediol or placebo for 12 weeks. Additional 14 weeks of treatment followed with study subjects receiving either 30 mcg or 60 mcg of ER calcifediol or placebo. Participants remained at 30 mcg unless their iPTH remained >70 pg/mL, total 25(OH)D3<65 ng/mL, and serum calcium <9.8 mg/ dL. In the latter case, the dose was increased to 60 mcg nightly. At the end of the 26-week treatment period, subjects entered an open-label extension study in which the placebo group was started on 30 mcg of ER calcifediol and subjects who met the above cut offs for iPTH and serum calcium concentrations could increase to 60 mcg at week 38.
At the end of 26 weeks, 80% of Study A had achieved serum 25(OH)D3 concentrations of at least 30 ng/mL, while only 3% of the placebo group had achieved the target serum concentrations. About 83% of Study B had achieved the target 25(OH)D3 serum concentrations compared to only 7% in the placebo group. The changes were statistically significant (p<0.001). Subjects that went on to the extension study (week 26-52) achieved goal 25(OH)D3 concentrations of >30 ng/mL within four weeks of initiation. At the end of 26 weeks, more subjects (72%) treated with ER calcifediol achieved reductions in iPTH compared to 27% in the placebo group. Overall, the drug was well-tolerated and an equal number of patients in both the treatment group and placebo group experienced at least one TEAE. The most common side effects that the treatment group experienced more frequently than placebo subjects were anemia (4.9 vs 3.5 %), nasopharyngitis (4.9 vs 2.8%), increased serum creatinine (4.9 vs. 1.4%), and dyspnea (4.2 vs 2.8 %), respectively.
The ER calcifediol study was the only study with a relatively large number of patients with more than 100 patients in one study arm. The results from the ER calcifediol study may be more applicable to clinical practice as the results from this study are more realistic of what could be seen in the clinical setting. Cost is also a limitation as one calcifediol capsule has a AWP unit price of $37.12. Cholecalciferol is over the counter and costs less than $10 per bottle. Clinicians should take patients’ socioeconomic levels into consideration when prescribing calcifediol over cholecalciferol. Overall, calcifediol is a relatively safe drug as the adverse effect profile is similar compared to placebo although the statistical significance of these comparisons was not reported. Although the serum creatinine did increase, there were no other reported adverse effects on renal function [7].
Conclusion Calcifediol is a prohormone of calcitriol approved for treatment of SHPT. It is an effective agent to replete vitamin D stores more rapidly compared to cholecalciferol. Areas for further research include comparative trials with calcimemetics like cinacalcet and the newly FDA approved etelcalcetide. Other outcomes that could be studied include the effect on mortality, cardiovascular disease and bone fractures. Randomized and controlled studies are needed to compare its effect and cost when compared with other vitamin D analogues.
Patients were randomized to two different study groups: A and B. The total study duration was 52 weeks long. Each study group was randomized in a 2:1 ratio to receive either 30 mcg ER calcifediol or placebo for 12 weeks. Additional 14 weeks of treatment followed with study subjects receiving either 30 mcg or 60 mcg of ER calcifediol or placebo. Participants remained at 30 mcg unless their iPTH remained >70 pg/mL, total 25(OH)D3<65 ng/mL, and serum calcium <9.8 mg/ dL. In the latter case, the dose was increased to 60 mcg nightly. At the end of the 26-week treatment period, subjects entered an open-label extension study in which the placebo group was started on 30 mcg of ER calcifediol and subjects who met the above cut offs for iPTH and serum calcium concentrations could increase to 60 mcg at week 38.
At the end of 26 weeks, 80% of Study A had achieved serum 25(OH)D3 concentrations of at least 30 ng/mL, while only 3% of the placebo group had achieved the target serum concentrations. About 83% of Study B had achieved the target 25(OH)D3 serum concentrations compared to only 7% in the placebo group. The changes were statistically significant (p<0.001). Subjects that went on to the extension study (week 26-52) achieved goal 25(OH)D3 concentrations of >30 ng/mL within four weeks of initiation. At the end of 26 weeks, more subjects (72%) treated with ER calcifediol achieved reductions in iPTH compared to 27% in the placebo group. Overall, the drug was well-tolerated and an equal number of patients in both the treatment group and placebo group experienced at least one TEAE. The most common side effects that the treatment group experienced more frequently than placebo subjects were anemia (4.9 vs 3.5 %), nasopharyngitis (4.9 vs 2.8%), increased serum creatinine (4.9 vs. 1.4%), and dyspnea (4.2 vs 2.8 %), respectively.
The ER calcifediol study was the only study with a relatively large number of patients with more than 100 patients in one study arm. The results from the ER calcifediol study may be more applicable to clinical practice as the results from this study are more realistic of what could be seen in the clinical setting. Cost is also a limitation as one calcifediol capsule has a AWP unit price of $37.12. Cholecalciferol is over the counter and costs less than $10 per bottle. Clinicians should take patients’ socioeconomic levels into consideration when prescribing calcifediol over cholecalciferol. Overall, calcifediol is a relatively safe drug as the adverse effect profile is similar compared to placebo although the statistical significance of these comparisons was not reported. Although the serum creatinine did increase, there were no other reported adverse effects on renal function [7].
Conclusion Calcifediol is a prohormone of calcitriol approved for treatment of SHPT. It is an effective agent to replete vitamin D stores more rapidly compared to cholecalciferol. Areas for further research include comparative trials with calcimemetics like cinacalcet and the newly FDA approved etelcalcetide. Other outcomes that could be studied include the effect on mortality, cardiovascular disease and bone fractures. Randomized and controlled studies are needed to compare its effect and cost when compared with other vitamin D analogues.