A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease

by Selleckchem | Jul 20 2023

Background: Five types of HIF-PHIs have been authorized for anemia treatment in CKD patients in China and Japan. These are enarodustat, roxadustat, daprodustat, vadadustat, and molidustat. How effectively they compare to ESAs about clinical results in CKD-DD patients is uncertain. This study examined the RCT evidence about the benefits and risks of HIF-PHIs and ESAs in dialysis CKD patients.

Methods: We conducted an extensive investigation and network meta-analysis of RCTs. In these RCTs, patients with CKD-DD received one of five different HIF-PHI or ESAs, a placebo, and no medical intervention. Outcomes included hemoglobin, iron parameters, and adverse events, and there were four weeks of follow-up at least. A frequentist framework for multivariate random effects meta-analyzed the results. The effect sizes of categorical variables were displayed as odds ratios. Mean differences were employed for computing continuous outcomes with common units; otherwise, standardized mean differences were applied. The Cochrane tool evaluated the bias risk in RCTs.

Results: 26 RCTs with 14945 patients were qualified for inclusion. Compared to the placebo, HIF-PHIs and ESAs dramatically boosted hemoglobin without affecting serum iron. Roxadustat performed better hemoglobin levels than ESAs (MD 0.32, 95% CI 0.10 to 0.53) and daprodustat (0.46, 0.09 to 0.84). Roxadustat (91.8%) was the top hemoglobin treatment among all medical interventions, as determined by the SUCRA ranking. However, roxadustat caused more thrombosis and hypertension than ESAs (1.61, 1.22 to 2.12) and vadadustat (1.36, 1.01 to 1.82). The lowest rates of hypertension and thrombosis were seen in molidustat (80.7%) and ESAs (88.5%). Compared with a placebo, ESAs and HIF-PHIs all affected TSAT levels. Except for molidustat, the other four HIF-PHIs impact different iron parameters. Regarding ferritin reduction, roxadustat (90.9%) and daprodustat (60.9%) came out on top. Enarodustat (80.9%) and roxadustat (74%) placed best and second in lowering hepcidin levels. The former two medicines for TIBC improvement were vadadustat (98.7%) and enarodustat (80.9%).

Conclusion: The most effective treatment for hemoglobin correction is roxadustat. The superior efficacy of reducing hepcidin makes roxadustat and enarodustat appropriate for patients with inflammation. However, the increased risk of hypertension and thrombosis associated with roxadustat should be noted. In patients at risk for hypertension and thrombosis, molidustat and ESAs may be preferable options. When administering roxadustat and daprodustat, clinicians should check ferritin to assess iron storage. Lower TSAT in patients receiving HIF-PHIs and ESAs treatment suggests intravenous iron supplements are needed.

Comments:

The study you described aimed to compare the effectiveness and safety of five different hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) and erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in chronic kidney disease patients on dialysis (CKD-DD). The researchers conducted a network meta-analysis of randomized controlled trials (RCTs) and evaluated various outcomes such as hemoglobin levels, iron parameters, and adverse events.

Here are the key findings from the study:

1. Hemoglobin Boost: Compared to a placebo, both HIF-PHIs and ESAs significantly increased hemoglobin levels in CKD-DD patients.

2. Hemoglobin Levels: Roxadustat showed superior performance in increasing hemoglobin levels compared to ESAs and daprodustat. Roxadustat was ranked highest among all the interventions.

3. Adverse Events: Roxadustat was associated with a higher risk of thrombosis and hypertension compared to ESAs and vadadustat. Molidustat and ESAs had the lowest rates of hypertension and thrombosis.

4. Iron Parameters: ESAs and HIF-PHIs, except for molidustat, influenced transferrin saturation (TSAT) levels compared to a placebo. Roxadustat and daprodustat were most effective in reducing ferritin levels. Roxadustat and enarodustat showed the greatest reduction in hepcidin levels. Vadadustat and enarodustat demonstrated the most improvement in total iron-binding capacity (TIBC).

5. Clinical Recommendations: Roxadustat was identified as the most effective treatment for hemoglobin correction. Roxadustat and enarodustat were considered suitable for patients with inflammation due to their superior efficacy in reducing hepcidin levels. However, the increased risk of hypertension and thrombosis associated with roxadustat should be monitored. For patients at risk of hypertension and thrombosis, molidustat and ESAs may be preferable. Clinicians should assess ferritin levels when using roxadustat and daprodustat, and lower TSAT levels indicate a need for intravenous iron supplements.

It's important to note that these findings are based on the analysis of existing RCTs and may not capture all potential factors or individual patient characteristics. Therefore, clinical decision-making should consider the specific needs and circumstances of each patient. Consulting with a healthcare professional is crucial for determining the most appropriate treatment approach for anemia in CKD-DD patients.