Effects of active vitamin D analogs and calcimimetic agents on PTH and bone mineral biomarkers in hemodialysis patients with SHPT: a network meta-analysis.

Objective: Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism.

Methods: We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes.

Results: Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions.

Conclusion: The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.