HIF-PHIs Versus ESAs for Anemia in Chronic Kidney Disease

By Victoria Socha - Last Updated: September 12, 2023

According to Qiong Huang, PhD, and colleagues, there are few data available on the comparative benefits and acceptability of hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) versus erythropoietin stimulating agents (ESAs) for the treatment of renal anemia in patients undergoing dialysis.

The researchers conducted a systematic review and network meta-analysis using the Cochrane Central Register of Controlled Trials, PubMed, Embase, Cochrane Library, MEDLINE, Web of Science, and clinicaltrials.gov databases.

The meta-analysis included 25 randomized controlled trials representing 17,204 participants. All of the trials were designed to achieve target levels of hemoglobin by adjusting the dose of HIF-PHIs. There were no significant differences between HIF-PHIs and ESAs in hemoglobin response at the dose-adjusted designed trials selected for comparison.

The risk of red blood cells transfusion was significantly lower with intervention with roxadustat compared with recombinant human erythropoietin (rhEPO): odds ratio [OR], 0.76; 95% CI, 0.56-0.93). The risk of increase in the discontinuation rate was higher with roxadustat and vadadustat compared with ESAs (roxadustat, OR, 1.58; 95% CI, 1.21-2.06 for rhEPO; OR, 1.66; 95% CI, 1.16-2.38) for darbepoetin alfa [DPO]; and OR, 1.76; 95% CI, 1.70-4.49 for methoxy polyethylene glycol [MPG]-EPO); vadadustat, OR, 1.71; 95% CI, 1.09-2.67 for rhEPO; OR, 1.79; 95% CI, 1.29-2.49 for DPO; and OR, 2.97, 95% CI, 1.62-5.46 for MPG-EPO).

There were no differences seen in adverse events and serious adverse events among trial participants. Compared with ESAS, HIF-PHIs were more effective in reducing levels of hepcidin and increasing total iron-binding capacity and levels of serum iron.

In summary, the authors said, “HIF-PHIs and ESAs have their characteristics and advantages in treating [patients with] anemia undergoing dialysis. With the selected dose-adjusted mode, some HIF-PHIs appeared to be a potential treatment for dialysis-dependent CKD patients when compared with rhEPO, due to its effectiveness in decreasing the risk of red blood cell transfusion rate or regulating iron or lipid metabolism while achieving target hemoglobin levels.”

Source: Frontiers in Pharmacology

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