Roxadustat Linked to Improved Iron Metabolism vs ESAs in Peritoneal Dialysis

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Use of roxadustat could be preferrable to erythropoiesis stimulating agents (ESAs) for improving iron metabolism in patients with peritoneal dialysis, according to results from a real-world study.

Results of the study, which enrolled more than 150 patients from China, suggests use of roxadustat was associated with significant improvements in hepcidin level and serum soluble transferrin receptor level, as well as a trend towards benefit in number of patients with functional iron deficiency, relative to ESAs.¹

“Information on the differences in the effects of roxadustat and ESAs on iron metabolism could help in selecting appropriate treatment options for [peritoneal dialysis] patients,” wrote investigators.¹

Since the class received its first approval in 1989, ESAs have ascended to a role as standard of care for anemia in patients with chronic kidney disease (CKD).² Although ESAs have become a staple in the management of anemia in chronic kidney disease, use is associated with increased risk of iron metabolism disorders.¹ This, in addition to other factors, has driven the development of the oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) class and agents like roxadustat and daprodustat (Jesduvroq), which received approval from the US Food and Drug Administration for treatment of anemia in patients with CKD who are on dialysis in February 2023.³

Despite not receiving approval in the US, roxadustat boasts approvals from regulatory agencies in the European Union, China, Japan, and other countries for a for the treatment of anemia of CKD in adult patients on dialysis and not on dialysis.⁴

In the current study, a team led by Dong Sun, of Xuzhou Medical University, sought to evaluate the impact of roxadustat use relative to ESAs on iron metabolism in patients using peritoneal dialysis. With this in mind, investigators designed a prospective, nonrandomized controlled trial aimed at comparing changes in iron biomarker levels among the aforementioned patient population.¹

A monocentric trial conducted at the Xuzhou Medical University, the trial enrolled patients aged 18-75 years, who had received stable peritoneal dialysis for more than 6 weeks, met the clinical diagnosis criteria for renal anemia, and had not been receiving ESAs, roxadustat, or iron supplementation within the 6 weeks prior to enrollment. Overall, 391 patients were assessed for eligibility and total of 159 patients underwent randomization, with 106 randomized to roxadustat and 53 randomized to ESAs. Of note, patients randomized to the ESA arm received generic epoetin alpha.¹

The primary outcomes of interest for the trial were changes from baseline to week 24 for hepcidin, serum soluble transferrin receptor (sTFR), serum iron, serum ferritin (sFt), transferrin saturation (TSAT), total iron binding capacity (TIBC), and the proportion of patients with absolute iron deficiency, which was defined as a TSAT of less than 20% and sFt less than 100 ng/mL.¹

Upon analysis, results suggested roxadustat was associated with a significantly decreased hepcidin level (difference, −20.09 ng/mL; 95% Confidence Interval [CI], −30.26 to −9.92; P <.01) and an attenuated increase in sTFR level (difference, − 7.87 nmol/L; 95% CI, −12.11 to −3.64; P <.01). Results also indicated use was associated with a nonsignificant reduction in the proportion of patients with functional iron deficiency (11.43% vs 33.33%) relative to use of ESAs. Analysis of safety outcomes suggested there were no significant difference in safety between the ESA and roxadustat groups during the study.¹

“This 24-week prospective cohort study comparing the efficacy of roxadustat and ESAs in [peritoneal dialysis] patients showed the benefit of roxadustat in improving iron metabolism,” investigators added.¹ “In addition to its inhibitory effect on hepcidin, roxadustat also induces the expression of molecules required for iron circulation. Thus, the increased iron consumption observed in the roxadustat group may be attributable not only to enhanced hematopoietic production, but also to improved iron utilization efficiency.”

References:

1. Zhang X, Jia R, Zheng Z, et al. Effect of roxadustat on iron metabolism in patients with peritoneal dialysis: a real-world 24-week study. Eur J Med Res. 2023;28(1):489. Published 2023 Nov 7. doi:10.1186/s40001-023-01465-0
2. Erythropoiesis stimulating agents (esas) for treatment of anemia in adults with CKD including patients on dialysis and patients not on dialysis. CMS.gov Centers for Medicare & Medicaid Services. Accessed November 28, 2023. https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&NCAId=245
3. Walter K, Campbell P. DAPRODUSTAT receives FDA approval for anemia caused by CKD on dialysis. HCP Live. February 2, 2023. Accessed November 28, 2023. https://www.hcplive.com/view/fda-daprodustat-patients-anemia-ckd-dialysis.
4. Astellas Pharma. Astellas to Present New Research Further Supporting Roxadustat Safety in the Treatment of Symptomatic Anemia of Chronic Kidney Disease at 59th ERA Congress 2022 . Astellas Pharma. May 16, 2022. Accessed November 28, 2023. https://www.astellas.com/en/system/files/news/2022-05/20220516_en_1.pdf.