The Efficacy and Safety of Roxadustat for Anemia in Hemodialysis Patients with Chronic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Patients undergoing hemodialysis (HD) for chronic kidney disease (CKD) often encounter anemia. Roxadustat has not only undergone phase II-III clinical trials in patients suffering from CKD and undergoing HD; a number of post-marketing clinical studies have been conducted using the drug. This article was to assess the effectiveness and safety of roxadustat in managing anemia among patients with CKD undergoing HD.

Methods: A thorough search was performed across eight databases, including PubMed, Web of Science, Cochrane Library, Embase, Wan Fang, China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQ VIP), and SinoMed to identify randomized clinical trials (RCTs) examining the effectiveness and safety of roxadustat in managing anemia among individuals suffering from CKD and undergoing HD. This search included studies from the inception of these databases to April 2023.

Results: Two phase II, one phase III, and 16 post-marketing studies with 1688 participants were included. Serum iron (SI), transferrin, and total iron-binding capacity (TIBC) levels changed from baseline (∆SI, ∆transferrin, and ∆TIBC) and were significantly more increased for roxadustat than for erythropoiesis-stimulating agents (ESAs): MD 2.55, (95% CI 1.51 to 3.60), p < 0.00001; MD 0.55, (95% CI 0.41 to 0.69), p < 0.00001; and MD 6.54, (95% CI 4.50 to 8.59), p < 0.00001, respectively. Roxadustat was not inferior to ESAs with regard to increasing Hb (∆Hb) levels [MD 1.17 (95% CI 0.71 to 1.63), p < 0.00001] (g/dL). No statistically significant distinctions of the ∆ferritin, ∆hepcidin, and transferrin saturation (TSAT) from baseline (∆TSAT) level were identified between roxadustat and ESAs. C-reactive protein (CRP) levels changed from baseline (∆CRP) and were significantly more reduced for roxadustat than for ESAs. As for safety, the analysis indicated no notable difference in the occurrence of adverse events (AEs) and serious adverse events (SAEs) between roxadustat and ESAs.

Conclusions: This meta-analysis demonstrated that roxadustat outperformed ESAs in enhancing SI, transferrin, and TIBC levels while also decreasing CRP levels. Roxadustat was not inferior to ESAs in terms of improving Hb levels and safety. These findings suggest that roxadustat was well tolerated and a potent alternative to ESAs in managing anemia among patients suffering from CKD and undergoing HD.

Keywords: anemia; chronic kidney disease; hemodialysis; meta-analysis; roxadustat.

Figure 1

Flowchart of this study.

Figure 2

Risk-of-bias assessment using the Cochrane Risk-of-Bias tool. Various colors and symbols denote distinct levels of bias risk; specifically, green and “+” represent a low risk, yellow and “?” signify an unclear risk, red and “−” denote a high risk. Bars represent the overall bias risk associated with each item. Circles represent the bias risk of each item corresponding to each study.

Figure 3

The forest graph of ∆Hb (g/dL). The green square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results.

Figure 4

The forest graph of ∆SI (umol/L, ug/dL, mmol/L, or ug/mL). The green square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results.

Figure 5

The forest graph of ∆hepcidin (ng/mL). The green square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results.

Figure 6

The forest graph of ∆ferritin (ng/mL). The green square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results. The arrow indicates that the 95% CI for the study’s effect size is outside the graphical range, and the excess is indicated by the arrow.

Figure 7

The forest graph of ∆transferrin (g/L). The green square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results.

Figure 8

The forest graph of ∆TIBC (umol/L or ug/dL). The green square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results.

Figure 9

The forest graph of ∆TSAT (%). The green square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results.

Figure 10

The forest graph of ∆CRP (mg/L). The green square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results.

Figure 11

The forest graph of AEs. The blue square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results.

Figure 12

The forest graph of SAEs. The blue square represents the point estimate of the effect size of each study, the line segment length represents the 95% CI of the effect size of each study, the diamond represents the summary results of the meta-analysis synthesis of each study, and the diamond width represents the 95% CI of the effect size of the summary results.

Figure 13

Publication bias analysis. The dots in the funnel plot represent the included studies, the horizontal axis represents the effect size, the vertical axis represents the s.e., the vertical line in the middle represents the ideal effect size, and the two diagonal lines represent the 95% CI.