OBJECTIVES: Patients with chronic kidney disease (CKD) are at risk for anaemia. Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) stimulate erythropoiesis and improve iron metabolism. Although erythropoiesis-stimulating agents (ESAs) are the standard of care for anaemia of CKD, HIF-PHIs may present an effective alternative. We conducted a systematic literature review to assess the available evidence on the efficacy and safety of HIF-PHI treatment of anaemia of CKD.

METHODS: We searched Embase, MEDLINE, and CENTRAL from database inception through January 11, 2022; conference proceedings from the previous 3 years; and ClinicalTrials.gov. Included studies were phase 3 randomized controlled trials (RCTs) of roxadustat, daprodustat, vadadustat, or molidustat, conducted in adults (≥18 years) with anaemia of CKD, published in English. Efficacy and safety data were extracted.

RESULTS: The database searches yielded 562 results; an additional 26 were identified from conference proceedings. From all combined records, 28 unique RCTs were eligible for inclusion. Of these, 12 assessed roxadustat, 7 daprodustat, 6 vadadustat, and 3 molidustat; comparators included darbepoetin alfa (DA), epoetin alfa (EA), methoxy polyethylene glycol–epoetin beta (MPG-EPO), and placebo.

Among non–dialysis-dependent patients, HIF-PHIs were non-inferior to DA or MPG-EPO for change from baseline in haemoglobin levels at Weeks 28–52. In the 1 trial that assessed efficacy beyond 1 year (DOLOMITES), improvements in haemoglobin levels with roxadustat were maintained over 104 weeks of treatment. Among dialysis-dependent patients, HIF-PHIs were non-inferior to DA for change from baseline in haemoglobin levels at Weeks 28–52 of treatment. For the same outcome, in 2 trials (HIMALAYAS and ROCKIES), roxadustat was non-inferior to EA (P<0.05). Across the studies, the frequencies of adverse events and discontinuations were similar between HIF-PHIs and ESAs.

CONCLUSIONS: Based on a qualitative assessment, efficacy of HIF-PHIs appeared comparable to that of ESAs, while safety profiles were similar between these drug classes.