Ni Li-Hua, Yuan Cheng, Song Kai-Yun, Wang Xiao-Chen, Chen Si-Jie, Wang Li-Ting, Zhang Yu-Xia, Liu Hong, Liu Bi-Cheng, Tang Ri-Ning
Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing 210009, China.
Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
Ann Transl Med. 2019 Jul;7(14):322. doi: 10.21037/atm.2019.05.84.
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).
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.
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.
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.
我们进行了一项网状Meta分析（NMA），以评估西那卡塞、活性维生素D以及西那卡塞联合活性维生素D治疗慢性肾脏病（CKD）患者继发性甲状旁腺功能亢进（SHPT）的疗效和安全性。
使用Cochrane图书馆、PubMed、EMBASE、Web of Science、谷歌学术、中国知网（CNKI）和万方数据库进行系统的文献检索。总共八项随机对照试验（RCT）、1443例患者符合本Meta分析的纳入标准。进行成对Meta分析以评估全段甲状旁腺激素（iPTH）、钙、磷等的达标情况，以及西那卡塞联合活性维生素D与单用活性维生素D的死亡率和安全性。然后，采用NMA评估活性维生素D及对照组中不同药物给药的安全性和疗效。
成对Meta分析结果显示，与活性维生素D单药治疗相比，西那卡塞联合活性维生素D虽未改善患者生存率，但显著提高了血钙达标率[相对危险度（RR）=1.82，95%置信区间（CI）：1.51 - 2.21，P<0.00001]。此外，值得注意的是，与其他治疗相应的发生率相比，西那卡塞联合活性维生素D治疗呕吐的发生率显著增加（RR =2.07，95%CI：1.18 - 3.65，P =0.01）。通过直接和间接比较，NMA得出以下结果：（I）与口服或静脉注射（IV）维生素D相比，单用活性维生素D口服增加了死亡率；（II）西那卡塞单药治疗增加了低钙血症风险，西那卡塞联合活性维生素D时该风险更高。然而，由于预测区间（PrI）越过无效线，这些结果应谨慎对待。
这项成对Meta分析和NMA对目前使用的CKD - SHPT治疗干预措施进行了全面分析。该网状分析通过纳入少量试验的分析确定了一些排名靠前的干预措施；这些干预措施值得在精心设计的RCT背景下进行更大规模的进一步研究。
