Summary

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• This summary is based on the review of seven systematic review(s)/meta-analysis(es). ^[1-7]
• Vadadustat: Vadadustat significantly increased the hemoglobin (Hb) response rate compared to placebo, with a relative risk (RR) of 5.27 (95% confidence interval (CI), 2.69 to 10.31). Additionally, it showed a greater mean increase in Hb levels from baseline, with a mean difference (MD) of 1.28 (95% CI, 0.83 to 1.73). However, Vadadustat exhibited a reduction in Hb response compared to erythropoiesis stimulating agents (ESAs) (RR: 0.88, 95% CI: 0.82-0.94).
• Vadadustat demonstrated improvements in iron parameters, including a decrease in hepcidin (MD: -36.62, 95% CI: -54.95 to -18.30) and ferritin (MD: -56.24, 95% CI: -77.37 to -35.11), alongside an increase in iron-binding capacity (MD: 24.38, 95% CI: 13.69 to 35.07).
• Vadadustat was associated with an increased risk of nausea and diarrhea compared to placebo or darbepoetin alfa, but there was no significant increase in the risk of serious adverse events, including all-cause mortality, cardiac events, and nonfatal stroke.
• Hypoxia-inducible factor (HIF) - (involving 17,204 participants) prolyl hydroxylase domain inhibitors (PHIs) in general showed no significant differences in overall adverse events and serious adverse events compared to ESAs, but there was an increased incidence of gastrointestinal disorders, including nausea, diarrhea, and hyperkalemia, as well as higher risks of vomiting, headache, and thrombosis compared to ESAs.
• The reviewed studies focus on chronic kidney disease (CKD) patients, both on dialysis and not undergoing dialysis, with subgroup considerations highlighting no significant differences in Hb response between HIF-PHIs and ESAs in achieving target Hb levels in dialysis patients. Roxadustat and enarodustat were found to be more suitable for patients with inflammation due to superior hepcidin reduction, while molidustat and ESAs may be preferred for patients at higher risk of hypertension and thrombosis.