Secondary hyperparathyroidism (SHPT) is a consequence of non-dialysis chronic kidney disease (ND-CKD), causing disturbances in metabolic parameters including increased phosphate and parathyroid hormone (PTH) and reduced calcium serum level, which can cause bone disease, extra-skeletal calcification and increased cardiac disease risk through vascular and visceral calcification. According to Kidney Disease Improving Global Outcomes (KDIGO) guidelines in 2017, treatment with paricalcitol is no longer recommended in early stage CKD due to increased risk of hypercalcemia. Prolonged release calcifediol (PRC) has been developed as a novel treatment for SHPT in ND-CKD. The objective of this study was to compare the efficacy and safety of PRC versus paricalcitol by assessing biomarkers such as PTH, calcium and phosphate.

To identify relevant randomized control trials (RCTs) to be included in the network meta-analysis (NMA), a systematic literature search was performed in PubMed. All analyses were performed with a frequentist random-effects NMA. Comparisons were made between the overall treatment effects of the two drugs (including all studies, with fixed and titrated dosage regimens), and between low fixed doses (PRC: 30 μg/day, paricalcitol: 1 μg/day) and high fixed doses (PRC: 60 μg/day, paricalcitol: 2 μg/day).

Nine RCTs, comprising a total of 1,426 patients, were included in the analyses. No statistically significant differences in PTH reduction were found. Paricalcitol showed significantly larger increases in calcium when overall effects and high doses were analyzed. No differences in effects on phosphate were observed. Although effect sizes and statistical significance levels vary somewhat across analyses, the general pattern of similar PTH reductions and larger increases in calcium from paricalcitol are observed in all analyses.

The non-inferiority shown by PRC in lowering PTH and the tendency to increase calcium serum levels observed with paricalcitol treatment indicates that PRC might be used as an equally effective but potentially safer alternative to paricalcitol in treating patients with SHPT.