Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: A systematic review and meta‐analysis

Liu, Junduo; Zhang, Afang; Hayden, John; Bhagavathula, Akshaya Srikanth; Alshehhi, Fatema; Rinaldi, Giulia; Kontogiannis, Vasileios; Rahmani, Jamal

doi:10.1016/j.phrs.2020.104747

Cited by 37 publications

(48 citation statements)

References 31 publications

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“…Although previous meta-analyses (28)(29)(30)(31)(32)(33)(34) have compared the efficacy and safety of roxadustat vs. placebo or ESA, the results showed that roxadustat was more effective than placebo and noninferior to ESA in correcting anemia in CKD patients. However, evidence for the results is still lacking and several new clinical trials have been conducted to compare roxadustat with placebo or ESA for the treatment of anemia in NDD-CKD or DD-CKD patients.…”

Section: Discussionmentioning

confidence: 95%

Safety and Efficacy of Roxadustat for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis

Liu

Jiang

et al. 2021

Front. Med.

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Background: Roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), has been used to treat anemia in patients with chronic kidney disease (CKD). However, its safety and efficacy remain controversial.Methods: The PubMed, EMBASE, Science Citation Index, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries databases were searched for relevant studies published up to April 2021. We identified randomized controlled trials (RCTs) comparing roxadustat with placebo or erythropoiesis-stimulating agents (ESAs) in anemia patients with CKD with or without dialysis.Results: Eleven studies including 6,631 patients met the inclusion criteria. In non-dialysis-dependent (NDD-) and dialysis-dependent (DD-) CKD patients, the total adverse events were not significantly different between the roxadustat and control (placebo for NDD-CKD patients and ESA for DD-CKD patients) groups [relative risk (RR) = 1.02, 95% confidence interval (CI) = 1.00, 1.04, P = 0.08, and RR = 1.22, 95% CI = 0.91, 1.64, P = 0.18, respectively], and the trial sequential analysis (TSA) confirmed the result in the NDD-CKD groups. No significant differences in hyperkalemia and infection incidences were found between roxadustat and placebo in the DD-CKD groups. The pooled results showed that roxadustat significantly increased the hemoglobin response rate compared with placebo in the NDD-CKD group and had an effect similar to that of ESA in the DD-CKD group. However, iron metabolism parameters did not seem to be obviously optimized by roxadustat.Conclusion: Roxadustat can be safely used in CKD patients. Oral roxadustat was more effective than placebo as a therapy for anemia in NDD-CKD patients and non-inferior to ESA in correcting anemia in DD-CKD patients. However, additional clinical trials are still needed to further prove whether roxadustat can optimize iron metabolism.

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Section: Discussionmentioning

confidence: 95%

Safety and Efficacy of Roxadustat for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis

Liu

Jiang

et al. 2021

Front. Med.

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“…During the last couple of years, several meta-analyses were conducted to estimate the efficacy and safety of roxadustat for renal anemia. However, only two phase III trials were enrolled in two of previously published meta-analyses (Liu et al, 2020;Zheng et al, 2020). Conclusions about the efficacy and safety of roxadustat were based on phase II trials exclusively in other meta-analyses (Zhong et al, 2018;Jia et al, 2019;Hu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Safe and Effective Treatment for Anemic Patients With Chronic Kidney Disease: An Updated Systematic Review and Meta-Analysis on Roxadustat

et al. 2021

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Background: Roxadustat is a new oral drug for anemia in chronic kidney disease (CKD). This study aimed to synthesize the evidence from randomized controlled trial (RCT)-based studies that estimated the efficacy and safety of roxadustat in anemia patients with non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD.Methods: We searched the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for related published studies. Moreover, we manually searched relevant pharmaceutical company websites and two international clinical trial registers to search for published and unpublished RCTs comparing roxadustat with erythropoietin-stimulating agents (ESAs) or placebo.Results: Fifteen RCTs (seven for DD-CKD patients, eight for NDD-CKD patients) were included in the meta-analysis, with 10,189 patients, 4,810 DD-CKD patients, and 5,379 NDD-CKD patients enrolled. Compared with ESAs (epoetin alfa or darbepoetin alfa) and placebo, roxadustat raised the hemoglobin level [weighted mean difference (WMD): 0.82 g/dL; 95% confidence interval (CI): 0.43–1.21], transferrin level (WMD: 0.5 g/L; 95% CI: 0.34–0.65), and TIBC level (WMD: 41.79 μg/dL; 95% CI: 38.67–44.92) and lowered the hepcidin level (WMD: −37.38 ng/ml; 95% CI: −46.63– −28.12) in both the DD-CKD and NDD-CKD patients with renal anemia. Roxadustat improved hemoglobin response and lowered the ferritin and TAST levels in the NDD-CKD patients but not in the DD-CKD patients. Furthermore, there was no difference between the treatment-emergent adverse events (TEAEs) of roxadustat and that of ESAs or placebo. But the incidence of serious TEAEs in the roxadustat group was significantly higher with NDD-CKD patients (OR: 1.15; 95% CI: 1.02–1.29).Conclusion: This study confirmed that roxadustat therapy could alleviate the anemia of DD-CKD and NDD-CKD patients by raising the hemoglobin level and regulating iron metabolism, but increased serious incidences of treatment-emergent adverse events (TEAEs) in NDD-CKD patients.

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“…Roxadustat, a potent, reversible, HIF-PHI that mimics the natural response to hypoxia results in target genes involved in erythropoiesis [31][32][33]. The meta-analysis of randomized controlled trials showed that Roxadustat can improve hemoglobin levels and iron metabolism in both dialysis-dependent and non-dialysis-dependent chronic kidney disease [34,35]. However, its long term efficacy and safety needs to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study

Zhang

Ren

Xue³

et al. 2021

BMC Nephrol

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Background Roxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear. Methods/Design This is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annual economic costs in two years. The data will be collected via Research electronic data capture (REDCap) based database as well as software-based dialysis registry of Sichuan province. The primary outcomes for the ROAD study participants will be compared with those in the dialysis registry cohort. Data at baseline and study follow up will also be compared to assess the association between Roxadustat and long-term clinical outcomes. Discussion The main objective of this study is to the assess long-term association of Roxadustat on MACE, all-cause mortality, socio-economic burden, safety in dialysis patients, which will provide guidance for designing further large randomized controlled trials to investigate this clinic question. Study registration The study has been registered in Chinese Clinical Trials Registry (ROAD, ROxadustat in treating Anemia in Dialysis patients, registration number ChiCTR1900025765) and provincial observational cohort database (Renal disEAse observational CoHort database, REACH, ChiCTR1900024926), registered 07 September 2019, http://www.chictr.org.cn.

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Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: A systematic review and meta‐analysis

Cited by 37 publications

References 31 publications

Safety and Efficacy of Roxadustat for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis

Safety and Efficacy of Roxadustat for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis

Safe and Effective Treatment for Anemic Patients With Chronic Kidney Disease: An Updated Systematic Review and Meta-Analysis on Roxadustat

Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study

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