Real-World Assessment: Clinical Effectiveness and Safety of Extended-Release Calcifediol

Abstract

<b><i>Introduction:</i></b> The safety and efficacy of extended-release calcifediol (ERC) as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI) has been demonstrated in prospective randomized clinical trials (RCTs). ERC (Rayaldee<sup>®</sup>) was approved by the Food and Drug Administration in 2016 on the basis of these prospective RCTs. The current retrospective study assessed the postlaunch data available with respect to ERC’s efficacy and safety in increasing serum 25-hydroxyvitamin D (25D) and reducing parathyroid hormone (PTH) in the indicated population. <b><i>Materials and Methods:</i></b> Medical records of 174 patients who met study criteria from 15 geographically representative United States nephrology clinics were reviewed for 1 year before and after initiation of ERC treatment. Enrolled subjects had ages ≥18 years, stage 3 or 4 CKD, and a history of SHPT and VDI. Key study variables included patient demographics, medication usage, and laboratory results, including serial 25D and PTH determinations. <b><i>Results:</i></b> The enrolled subjects had a mean age of 69.0 years, gender and racial distributions representative of the indicated population, and were balanced for CKD stage. Most (98%) received 30 mcg of ERC/day during the course of treatment (mean follow-up: 24 weeks). Baseline 25D and PTH levels averaged 20.3 ± 0.7 (standard error) ng/mL and 181 ± 7.4 pg/mL, respectively. ERC treatment raised 25D by 23.7 ± 1.6 ng/mL (<i>p</i> < 0.001) and decreased PTH by 34.1 ± 6.6 pg/mL (<i>p</i> < 0.001) with nominal changes of 0.1 mg/dL (<i>p</i> > 0.05) in serum calcium (Ca) and phosphorus (P) levels. <b><i>Discussion/Conclusion:</i></b> Analysis of postlaunch data confirmed ERC’s effectiveness in increasing serum 25D and reducing PTH levels without statistically significant or notable impact on serum Ca and P levels. A significant percentage of these subjects achieved 25D levels ≥30 mg/mL and PTH levels which decreased by at least 30% from baseline. Dose titration to 60 mcgs was rarely prescribed. Closer patient monitoring and appropriate dose titration may have led to a higher percentage of subjects achieving an increase in 25D levels to at least 50 ng/mL and a reduction in PTH levels of at least 30%.

Vitamin D and Secondary Hyperparathyroidism in Chronic Kidney Disease: A Critical Appraisal of the Past, Present, and the Future

“…The gradual elevation of 25-hydroxyvitamin D with ERC to levels as high as 92.5 ng/mL over a 26-week period had no adverse effects on safety parameters [ 42 , 68 ]. These trial data are supported by emerging real-world data by Fadda et al (2021) [ 69 ]. This study confirmed ERC’s effectiveness in increasing serum 25-hydroxyvitamin D and reducing PTH levels without a statistically significant or notable impact on serum calcium and phosphate levels (on average, calcium went from 9.2 ± 0.1 mg/dL to 9.3 ± 0.1 mg/dL and phosphate went from 3.8 ± 0.1 mg/dL to 3.9 ± 0.1 mg/dL).…”

“…VDR—vitamin D receptor, 24,25(OH)2D—24,25-dihydroxyvitamin D (inactive prohormone), 1,24,25(OH)3D—1,24,25 trihydroxyvitamin D (inactive hormone), Ca—calcium, P—phosphorus, FGF23—Fibroblast growth factor-23, PTH—parathyroid hormone, CYP27A1—25-hydroxylase, CYP27B1—1α-hydroxylase, CYP24A1—24-hydroxylase. Adapted from Cozzolino et al [ 41 ], Christensen et al [ 10 ], extended with data from Sprague et al [ 42 , 68 ] and Fadda et al [ 69 ].…”

Real-world assessment: effectiveness and safety of extended-release calcifediol and other vitamin D therapies for secondary hyperparathyroidism in CKD patients

“…These clinical trials have established the efficacy of ERC for increasing serum 25D levels and reducing PTH with minimal changes in serum Ca or P levels in adult patients with stage 3-4 CKD and VDI. Corresponding real-world clinical data have confirmed the data obtained from RCTs [24] but real-world comparative data are lacking. The lack of such comparative data led to the current evaluation of real-world clinical experience with the available treatment options to raise serum 25D and reduce elevated PTH during a 12-month period.…”

Extended-Release Calcifediol Effectively Raises Serum Total 25-Hydroxyvitamin D Even in Overweight Nondialysis Chronic Kidney Disease Patients with Secondary Hyperparathyroidism

“…Data from two real-world clinical studies (Studies 1 and 2) and two prospective RCTs (Studies 3 and 4) in CKD patients were analyzed to assess the influence of BW on the relative capabilities of vitamin D supplements and ERC to adequately raise 25OHD for effective management of SHPT. Real-world data were obtained from nondialysis patients with stage 3–5 CKD undergoing standard-of-care treatment at European facilities operated by Fresenius Medical Care (FMC) (Study 1) and from patients with stage 3–4 CKD, SHPT, and VDI from multiple USA clinics (Study 2; WIRB 1252915) [ 33 ]. Prospective data were obtained from two US RCTs conducted in patients with stage 3–4 CKD, SHPT, and VDI which examined short-term increases in serum 25OHD during ERC or cholecalciferol treatment (Study 3; NCT03588884; Advarra PRO00025210) or longer term increases in 25OHD with ERC as a function of BW (Study 4; NCT01651000, NCT01704079; Advarra PRO00007820) [ 34 ].…”