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. 2021 Jan 12:11:573645.
doi: 10.3389/fphar.2020.573645. eCollection 2020.

Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

Qiyan Zheng  1   2 , Yahui Wang  1   2 , Huisheng Yang  3 , Luying Sun  1   2 , Xinwen Fu  1   2 , Ruojun Wei  1   2 , Yu Ning Liu  1   2 , Wei Jing Liu  1   2   4
Affiliations

Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

Qiyan Zheng et al. Front Pharmacol. .

Abstract

Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients. Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs). Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, -0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, -0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group. Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.

Keywords: anemia; chronic kidney disease; daprodustat; meta-analysis; systematic review.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of literature search and selection.
FIGURE 2
FIGURE 2
Risk-of-bias summary of included randomized trials using the Cochrane risk-of-bias tool.
FIGURE 3
FIGURE 3
The meta-analysis results of daprodustat for △Hb. (A) The pooled results for NDD patients; (B) The pooled results for DD patients.
FIGURE 4
FIGURE 4
The meta-analysis results of daprodustat for △ferritin. (A) The pooled results for NDD patients; B: The pooled results for DD patients.
FIGURE 5
FIGURE 5
The meta-analysis results of daprodustat for △TSAT. (A) The pooled results for NDD patients; (B) The pooled results for DD patients.
FIGURE 6
FIGURE 6
The meta-analysis results of daprodustat for △TIBC. (A) The pooled results for NDD patients; (B) The pooled results for DD patients.
FIGURE 7
FIGURE 7
The meta-analysis results of daprodustat for SAEs. (A) The pooled results for NDD patients; (B) The pooled results for DD patients.
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