Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China.
Nephrol Dial Transplant. 2021 Aug 27;36(9):1603-1615. doi: 10.1093/ndt/gfaa110.
Chronic kidney disease (CKD) is an increasing public health issue. Anemia, which is a complication of CKD, is associated with reduced quality of life and increased morbidity and mortality. Currently quite a few clinical studies have been conducted to compare roxadustat with epoetin alfa [all for dialysis-dependent (DD) patients] or placebo [all for nondialysis-dependent (NDD) patients]. Our meta-analysis aimed to investigate the efficacy and safety of roxadustat for anemia in patients with CKD.
We thoroughly searched eight electronic resource databases for randomized controlled trials (RCTs) comparing the efficacy and safety between roxadustat versus epoetin alfa or placebo for the treatment of anemia in patients with CKD.
Four Phase 2 and two Phase 3 studies with 1010 participants were included. Hemoglobin (Hb) and transferrin levels were increased significantly in the roxadustat group versus those in the placebo {standard mean difference [SMD] 1.57 [95% confidence interval (CI) 1.17-1.98]; SMD 1.81 [95% CI 1.53-2.08]; respectively, both low-quality evidence} or epoetin alfa group [SMD 0.47 (95% CI 0.02-0.93), very low-quality evidence; SMD 1.05 (95% CI 0.81-1.29), low-quality evidence; respectively]. Hepcidin levels were reduced significantly in the roxadustat group versus those in the placebo [SMD -1.72 (95% CI -3.03 to -0.41), very low-quality evidence] or epoetin alfa group [SMD -0.23 (95% CI -0.43 to -0.02), low-quality evidence]. Ferritin and serum transferrin saturation (TSAT) levels were reduced significantly in the roxadustat group versus those in the placebo group [SMD -0.82 (95% CI -1.31 to -0.33); SMD -0.54 (95% CI -0.76 to -0.32), respectively; both low-quality evidence] and ferritin and TSAT levels in the roxadustat group were comparable to those in the epoetin alfa group [SMD 0.02 (95% CI -0.18-0.21); SMD 0.15 (95% CI -0.04-0.35), respectively, both low-quality evidence]. As for safety, the incidence of adverse events (AEs) in the roxadustat group was insignificantly different from that of the placebo group [risk ratio (RR) 0.99 (95% CI 0.83-1.18); P = 0.89, very low-quality evidence]. But the incidence of AEs in the roxadustat group was significantly higher than that in the epoetin alfa group [RR 1.25 (95% CI 1.01-1.54); P = 0.04, low-quality evidence]. There was no significant association between roxadustat and the incidence of serious AEs (SAEs) for both NDD and DD patients [RR 1.08 (95% CI 0.51-2.28) and RR 1.43 (95% CI 0.85-2.40), respectively, both very low-quality evidence].
In this meta-analysis of RCTs, we found evidence that after the oral administration of roxadustat, NDD patients' Hb levels were increased effectively and DD patients' Hb levels were maintained effectively. The risk of SAEs was not observed with the short-term use of roxadustat. These findings support roxadustat for the treatment of anemia in patients with CKD.
慢性肾脏病（CKD）是一个日益严重的公共卫生问题。贫血是 CKD 的一种并发症，与生活质量下降以及发病率和死亡率增加有关。目前已经有相当多的临床研究比较了罗沙司他与促红细胞生成素 alfa（均用于透析依赖（DD）患者）或安慰剂（均用于非透析依赖（NDD）患者）。我们的荟萃分析旨在研究罗沙司他治疗 CKD 患者贫血的疗效和安全性。
我们全面检索了八个电子资源数据库，以查找比较罗沙司他与促红细胞生成素 alfa 或安慰剂治疗 CKD 患者贫血的疗效和安全性的随机对照试验（RCT）。
纳入了四项 2 期和两项 3 期研究，共 1010 名参与者。与安慰剂相比，罗沙司他组的血红蛋白（Hb）和转铁蛋白水平显著升高[标准均数差（SMD）1.57（95%置信区间[CI] 1.17-1.98）；SMD 1.81（95% CI 1.53-2.08）；均为低质量证据]或促红细胞生成素 alfa 组[SMD 0.47（95% CI 0.02-0.93），极低质量证据；SMD 1.05（95% CI 0.81-1.29），低质量证据]。与安慰剂相比，罗沙司他组的铁调素水平显著降低[SMD-1.72（95% CI -3.03 至 -0.41），极低质量证据]或促红细胞生成素 alfa 组[SMD-0.23（95% CI -0.43 至 -0.02），低质量证据]。与安慰剂相比，罗沙司他组的铁蛋白和血清转铁蛋白饱和度（TSAT）水平显著降低[SMD-0.82（95% CI -1.31 至 -0.33）；SMD-0.54（95% CI -0.76 至 -0.32），均为低质量证据]，且罗沙司他组的铁蛋白和 TSAT 水平与促红细胞生成素 alfa 组相当[SMD 0.02（95% CI -0.18 至 0.21）；SMD 0.15（95% CI -0.04 至 0.35），均为低质量证据]。关于安全性，罗沙司他组的不良事件（AE）发生率与安慰剂组无显著差异[风险比（RR）0.99（95% CI 0.83-1.18）；P=0.89，极低质量证据]。但罗沙司他组的 AE 发生率明显高于促红细胞生成素 alfa 组[RR 1.25（95% CI 1.01-1.54）；P=0.04，低质量证据]。罗沙司他与 NDD 和 DD 患者严重不良事件（SAE）的发生率之间没有显著关联[RR 1.08（95% CI 0.51-2.28）和 RR 1.43（95% CI 0.85-2.40），均为极低质量证据]。
在这项 RCT 的荟萃分析中，我们发现口服罗沙司他后，NDD 患者的 Hb 水平有效升高，DD 患者的 Hb 水平得到有效维持。短期使用罗沙司他没有观察到 SAE 的风险。这些发现支持罗沙司他用于治疗 CKD 患者的贫血。
