Efficacy and safety of cinacalcet and active vitamin D in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease: a network meta-analysis.

BACKGROUND: We conducted a network meta-analysis (NMA) to evaluate the efficacy and safety of cinacalcet, active vitamin D and cinacalcet plus active vitamin D in the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD). METHODS: A systematic literature search was performed using the Cochrane Library, PubMed, EMBASE, Web of Science, Google Scholar, China National Knowledge Internet (CNKI) and Wanfang databases. In total, eight randomized controlled trials (RCTs) with 1,443 patients were eligible for this meta-analysis. Pairwise meta-analysis was performed to evaluate the compliance of intact parathyroid hormone (iPTH), Ca, P, etc., and the mortality and safety of cinacalcet plus active vitamin D and active vitamin D alone. Then, NMA was used to estimate the safety and efficacy of the administration of active vitamin D and different drugs in the control group. RESULTS: The results of the pairwise meta-analysis revealed that compared with active vitamin D monotherapy, cinacalcet plus active vitamin D did not improve the survival of patients but significantly improved the blood calcium compliance rate [relative risk (RR) =1.82, 95% confidence interval (CI): 1.51-2.21, P<0.00001]. Furthermore, it is worth noting that compared with the corresponding incidence with other treatments, the incidence of vomiting was significantly increased with cinacalcet plus active vitamin D treatment (RR =2.07, 95% CI: 1.18-3.65, P=0.01). Through direct and indirect comparisons, the NMA revealed the following results: (I) compared with oral or intravenous (IV) administration of vitamin D, the solely oral administration of active vitamin D increased mortality, and (II) cinacalcet monotherapy increased the risk of hypocalcemia, and that risk was even higher for cinacalcet plus active vitamin D. However, the results should be treated with caution because the prediction interval (PrI) crossed the invalid line. CONCLUSIONS: This pairwise meta-analysis and NMA provided a comprehensive analysis of the currently utilized CKD-SHPT treatment interventions. This network identified some highly ranked interventions through analyses that were included in a small number of trials; these interventions merit further examination on a larger scale in the context of well-designed RCTs.