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

Abstract

Introduction Extended-release calcifediol (ERC), active vitamin D hormones and analogs (AVD) and nutritional vitamin D (NVD) are commonly used therapies for treating secondary hyperparathyroidism (SHPT) in adults with stage 3–4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). Their effectiveness for increasing serum total 25-hydroxyvitamin D (25D) and reducing elevated plasma parathyroid hormone (PTH), the latter of which is associated with increased morbidity and mortality, has varied across controlled clinical trials. This study aimed to assess real-world experience of ERC and other vitamin D therapies in reducing PTH and increasing 25D. Methods Medical records of 376 adult patients with stage 3–4 CKD and a history of SHPT and VDI from 15 United States (US) nephrology clinics were reviewed for up to 1 year pre- and post-ERC, NVD or AVD initiation. Key study variables included patient demographics, concomitant usage of medications and laboratory data. The mean age of the study population was 69.5 years, with gender and racial distributions representative of the US CKD population. Enrolled patients were grouped by treatment into three cohorts: ERC (n = 174), AVD (n = 55) and NVD (n = 147), and mean baseline levels were similar for serum 25D (18.8–23.5 ng/mL), calcium (Ca: 9.1–9.3 mg/dL), phosphorus (P: 3.7–3.8 mg/dL) and estimated glomerular filtration rate (eGFR: 30.3–35.7 mL/min/1.73m2). Mean baseline PTH was 181.4 pg/mL for the ERC cohort versus 156.9 for the AVD cohort and 134.8 pg/mL (p < 0.001) for the NVD cohort. Mean follow-up during treatment ranged from 20.0 to 28.8 weeks. Results Serum 25D rose in all cohorts (p < 0.001) during treatment. ERC yielded the highest increase (p < 0.001) of 23.7 ± 1.6 ng/mL versus 9.7 ± 1.5 and 5.5 ± 1.3 ng/mL for NVD and AVD, respectively. PTH declined with ERC treatment by 34.1 ± 6.6 pg/mL (p < 0.001) but remained unchanged in the other two cohorts. Serum Ca increased 0.2 ± 0.1 pg/mL (p < 0.001) with AVD but remained otherwise stable. Serum alkaline phosphatase remained unchanged. Conclusions Real-world clinical effectiveness and safety varied across the therapies under investigation, but only ERC effectively raised mean 25D (to well above 30 ng/mL) and reduced mean PTH levels without causing hypercalcemia.

Improving Kidney Disease Care: One Giant Leap for Nephrology

“…Clinical trials show dose-dependent increases in 25(OH)D and physiological increases in 1,25(OH)2D, with sustained reduction in parathyroid hormone and minimal impact on mineral balance [36]. Meanwhile, emerging data from real-world clinical experience with extended-release calcifediol for patients with stage 3 or 4 CKD suggest that it is comparable to active vitamin D analogues for controlling parathyroid hormone levels, with the added benefit of replenishing 25(OH)D [37]. In practice, patients with serum 25(OH)D levels ≥ 30 ng/mL and normal calcium, phosphorus, and parathyroid hormone may not require therapy.…”

Vitamin D and Chronic Kidney Disease Association with Mineral and Bone Disorder: An Appraisal of Tangled Guidelines

“…Furthermore, the goal should not be complete normalization of iPTH levels. New developments, such as extended-release formulations [ 109 , 110 ] (which correct both vitamin D deficiency and are more effective than native in decreasing iPTH levels) and new analogs, biomarkers, molecular targets, and even renal pathologies [ 111 , 112 , 113 , 114 , 115 , 116 , 117 ], may then help us better define optimal VD and iPTH levels or the best formulation at different CKD stages [ 92 , 107 , 109 ], thereby directing us towards an improved, personalized medicine. It is possible that the approaches that we took to correct VD deficiency are at least partially wrong and that current interventions with native and/or active VD were not properly targeted at more effective goals.…”

Mini review: A reevaluation of nutritional vitamin D in the treatment of chronic kidney disease

“…[42] Meanwhile, ERC was able to reduce PTH levels effectively without oversuppression. [43] There were several differences between ERC and NVD: (a) ERC is more bioavailable and water soluble; (b) ERC does not need to be metabolized by the liver; (c) ERC is closely bound with DBP in serum to improve the pharmacological effect of serum 25(OH)D. [44] 6. A shift in the understanding of vitamin D Here, we review our historical understanding of vitamin D deficiency in CKD.…”

“…There were several differences between ERC and NVD: (a) ERC is more bioavailable and water soluble; (b) ERC does not need to be metabolized by the liver; (c) ERC is closely bound with DBP in serum to improve the pharmacological effect of serum 25(OH)D. [ 44 ]…”