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.
Highlights
Chronic kidney disease (CKD), as a major global health problem, is estimated to affect 8–16% of adult populations globally (Stanifer et al, 2016; Chen et al, 2019)
We included clinical studies that satisfied the following criteria: 1) type of study limited to randomized controlled trials (RCTs); 2) participants in the included studies were anemia with CKD (KDIGO Clinical Practice Guideline Working Group, 2012); 3) daprodustat as an intervention arm; 4) the control arm receiving other ways to contrast with daprodustat; 5) the outcome indicators were focused on: 1) Hb, ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC) and vascular endothelial growth factor (VEGF), 2) serious adverse events (SAEs)
The pooled results showed that for both non-dialysis dependent (NDD) patients (Figure 3A) and DD patients (Figure 3B), △Hb levels were significantly higher in the daprodustat group than that in placebo cohort (MD 1.73, [95% confidence interval (95% CI), 0.34 to 3.12], p 0.01; mean difference (MD) 1.88, [95% CI, 0.68 to 3.09], p 0.002; respectively), but there was no significant difference between daprodustat and recombinant human erythropoietin (rhEPO) in terms of changes in Hb levels (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)
Summary
Chronic kidney disease (CKD), as a major global health problem, is estimated to affect 8–16% of adult populations globally (Stanifer et al, 2016; Chen et al, 2019). Current treatments for anemia in CKD mainly require recombinant human erythropoietin (rhEPO) or its analogs (erythropoiesis stimulating agents [ESAs]) and iron supplementation (intravenous and/or oral) (KDIGO Clinical Practice Guideline Working Group, 2012; US Food and Drug Administration, 2011; Shepshelovich et al, 2016). While these therapies can greatly benefit patients by improving their quality of life and reducing the need for blood transfusions (Finkelstein et al, 2009; Parfrey et al, 2009), each has significant limitations, such as the inconvenience of subcutaneous injection that impact its use. Safer and more effective drugs are continuously being developed by a number of pharmaceutical companies for treatment of anemia in CKD patients
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