Efficacy and safety of roxadustat for anaemia in dialysis‐dependent and non‐dialysis‐dependent chronic kidney disease patients: A systematic review and meta‐analysis

Abstract

Aims Renal anaemia is a common complication of chronic kidney disease (CKD). Roxadustat is the first‐in‐class oral hypoxia‐inducible factor prolyl hydroxylase inhibitor for the treatment of anaemia. In this systematic review, we aimed to investigate the efficacy and safety of roxadustat in the treatment of anaemia in CKD patients. Methods PubMed, Cochrane Library, Embase, and http://ClinicalTrials.gov databases were searched from their inception to February 2021 for randomised controlled trials (RCTs) that compared the efficacy and safety of roxadustat to those of an erythropoiesis‐stimulating agent (ESA) or a placebo in treating anaemia in CKD patients. Results Nine RCTs involving 2743 patients were found. The meta‐analysis showed that roxadustat increased haemoglobin (Hb) level by 0.91 g/dL (95% confidence interval [CI]: 0.47–1.34, P < .05), transferrin level by 0.50 mg/dL (95% CI: 0.34–0.65, P < .05), and total iron‐binding capacity by 50.64 μg/dL (95% CI: 36.21–65.07, P < .05) in CKD patients. Decreases in hepcidin (mean difference [MD] = −23.16, 95% CI: −37.12 to −9.19, P < .05) and ferritin (MD = ‐38.35, 95% CI: −67.41 to −9.29, P < .05) levels were also observed. There was no significant difference in the incidence of adverse events (AEs) (OR: 1.12, 95% CI: 0.95–1.32, P = .17) between the roxadustat and control groups; however, the incidence of serious AEs in the roxadustat group was significantly higher than that in the ESA group (OR: 1.33, 95% CI: 1.06–1.68, P < .05). Conclusion Roxadustat can significantly improve renal anaemia in CKD patients by increasing Hb level and iron metabolism. However, attention must be paid to the risk of SAEs during treatment.

Randomized Study on the Efficacy of Standard Versus Low Roxadustat Dose for Anemia in Patients on Peritoneal Dialysis

“…Third, recent meta-analysis indicated that standarddose roxadustat therapy could increase serious incidences of treatment-emergent adverse events compared with ESA in non-dialysis-dependent CKD population. 25,26 Taken together, more heterogeneous and long-term interventional studies should be performed to observe the effectiveness and safety of different initial-dose regimens and dosing-adjustment strategies for anemia correction.…”

Safety of HIF Prolyl-Hydroxylase Inhibitors for Anemia in Dialysis Patients: A Systematic Review and Network Meta-Analysis

“…Daprodustat may better influence DD-CKD patients' optimizing iron metabolism [18], and is not inferior to ESAs regarding ΔHb and cardiovascular diseases [31]. Nevertheless, some literature proposed that safety data of HIF-PHIs like Roxadustat is still emerging, and attention must be poured into the risk of TEAE, especially SAEs during therapy [42,52]. The above research is basically limited to studying a specific drug in HIF-PHI, and the safety is still controversial.…”

Luteolin can ameliorate renal interstitial fibrosis-induced renal anaemia through the SIRT1/FOXO3 pathway

“…However, this drug is not yet widely used in clinical practice and is associated with a risk of serious adverse events; for example, it can increase the prevalence of infections and cardiac, vascular, hematologic and lymphatic diseases. 8 In addition, 16% of patients show poor response. 9 Renal anaemia is still a refractory disease for which it is imperative to find new therapeutic targets and develop new therapeutic drugs.…”