The efficacy and safety of roxadustat treatment for anemia in patients with kidney disease: a meta-analysis and systematic review

Qie, Suhui; Jiao, Ning; Duan, Kunfeng; Li, Jingxin; Yang, Licong; Liu, Guoqiang

doi:10.1007/s11255-020-02693-7

Cited by 17 publications

(25 citation statements)

References 29 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: 96%

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: 96%

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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“…All published phase II trials indicate that HIF-PHI therapy is at least as efficacious as conventional ESA therapy in managing Hb levels in both nondialysis-dependent CKD (ND-CKD and dialysis-dependent (DD-CKD) patients [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. The meta-analysis of 26 randomized controlled trials involving 2804 patients with CKD comparing the use of HIF-PHIs versus ESAs or placebo in the treatment of renal anemia found HIF-PHIs superior to placebo and at least as efficacious as classic ESAs in the short term [ 5 ].…”

Section: Hypoxia-inducible Factor Inhibitorsmentioning

confidence: 99%

“…The meta-analysis of 26 randomized controlled trials involving 2804 patients with CKD comparing the use of HIF-PHIs versus ESAs or placebo in the treatment of renal anemia found HIF-PHIs superior to placebo and at least as efficacious as classic ESAs in the short term [ 5 ]. Likewise, a meta-analysis by Qie et al, including 1010 patients, showed that roxadustat has a higher mean Hb level than placebo or EPO [ 91 ]. HIF-PHIs have demonstrated efficacy and safety in phase 2 and 3 trials in several different cohorts of CKD patients with anemia who are either ND-CKD or DD.…”

Section: Hypoxia-inducible Factor Inhibitorsmentioning

confidence: 99%

“…Wang et al reported that among the included HIF-PHIs, roxadustat was associated with a favored effect on Hb compared to classic ESAs [ 5 ]. Roxadustat administration leads to increases in endogenous EPO levels, with peak increases 8–12 h postdose in healthy volunteers and patients with CKD [ 61 , 62 , 63 , 64 , 65 ] With a half-life of 10 h, roxadustat is administered three times weekly [ 91 ]. HIF-PHIs such as roxadustat offer the promise of decreased inflammation, a better use of existing iron stores, and an enhanced gastrointestinal absorption of oral iron, along with an acceptable safety profile.…”

Section: Hypoxia-inducible Factor Inhibitorsmentioning

confidence: 99%

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Current Status of Renal Anemia Pharmacotherapy—What Can We Offer Today

Borawski

Małyszko

Kwiatkowska

et al. 2021

JCM

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Chronic kidney disease (CKD) is one of the fastest-growing major causes of death internationally. Better treatment of CKD and its complications is crucial to reverse this negative trend. Anemia is a frequent complication of CKD and is associated with unfavorable clinical outcomes. It is a devastating complication of progressive kidney disease, that negatively affects also the quality of life. The prevalence of anemia increases in parallel with CKD progression. The aim of this review is to summarize the current knowledge on therapy of renal anemia. Iron therapy, blood transfusions, and erythropoietin stimulating agents are still the mainstay of renal anemia treatment. There are several novel agents on the horizon that might provide therapeutic opportunities in CKD. The potential therapeutic options target the hepcidin–ferroportin axis, which is the master regulator of iron homeostasis, and the BMP-SMAD pathway, which regulates hepcidin expression in the liver. An inhibition of prolyl hydroxylase is a new therapeutic option becoming available for the treatment of anemia in CKD patients. This new class of drugs stimulates the synthesis of endogenous erythropoietin and increases iron availability. We also summarized the effects of prolyl hydroxylase inhibitors on iron parameters, including hepcidin, as their action on the hematological parameters. They could be of particular interest in the out-patient population with CKD and patients with ESA hyporesponsiveness. However, current knowledge is limited and still awaits clinical validation. One should be aware of the potential risks and benefits of novel, sophisticated therapies.

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“…46 A 2021 meta-analysis of 8 phase 2 and 3 studies of roxadustat demonstrated significant increases vs. control (placebo and ESAs) in TIBC (P<0.00001) and serum iron level (p=0.05); significant reductions in hepcidin (P<0.0001) and ferritin (P<0.00001). 47 The global phase 3 program for roxadustat includes 4 studies in NDD-CKD patients (ALPS, ANDES, and OLYMPUS using placebo control; DOLOMITES using ESA control) and 4 studies in DD-CKD patients (HIMALAYAS, ROCKIES and SIERRAS using epoetin control; PYRENEES using epoetin or darbepoetin control). The first two publications 48,49 from the roxadustat global phase 3 program appeared in Kidney International Reports in 2021, accompanied by an editorial.…”

Section: Roxadustatmentioning

confidence: 99%

Treatment of Anemia in Kidney Disease: Beyond Erythropoietin

Wish

2021

Kidney International Reports

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The efficacy and safety of roxadustat treatment for anemia in patients with kidney disease: a meta-analysis and systematic review

Cited by 17 publications

References 29 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

Current Status of Renal Anemia Pharmacotherapy—What Can We Offer Today

Treatment of Anemia in Kidney Disease: Beyond Erythropoietin

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