Projected Long-Term Cost Savings with Roxadustat, a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (HIF-PHI), among Patients on Hemodialysis: Insights from a 100-Week Longitudinal Study

Background: HIF-PH inhibitors are attracting attention for their novel mechanisms of action. However, the cost of the starting dose of HIF-PH inhibitors is considerably higher than biosimilar ESA, and it may limit the use of them. Nevertheless, HIF-PH inhibitors demonstrate targeting capabilities across numerous genes, hinting at potential advantages extending beyond just anemia alleviation. Methods: Seventy-two hemodialysis (HD) patients receiving 9000 U/week of EPO were transitioned to roxadustat thrice weekly at 100 mg doses, titrated to maintain hemoglobin (Hb) levels between 10 to 12 g/dL. During the titration of roxadustat dosage, we carefully observed ferrokinetic and administered iron supplementation as necessary. Results: The initial dose of roxadustat was approximately 261 mg/week, equivalent to about 4,000 yen/week, well above EPO's cost of about 2,600 yen/week. Over time, the dose of roxadustat gradually decreased, and as shown in the figure, after 60 weeks, the cost of roxadustat was almost equal to that of EPO. during 100 weeks, the dose/cost of roxadustat decreased to about 60% from the initial dose. At the same time, GNRI decreased slightly from 92 ± 12.4 to 87 ± 8.9 and CRP increased from 0.3 ± 0.14 mg/dL to 0.8 ± 0.14 mg/dL, but without statistical significance. No serious adverse reactions were reported. Conclusion: Roxadustat, HIF-PH inhibitors, demonstrated the dose / cost reductions over long-term use. Given their reported cost-sparing advantages, HIF-PH inhibitors emerge as effective alternatives to ESA for managing anemia in HD patients. The observed reduction in cost over time subsequent to switching from EPO to roxadustat suggests underlying factors beyond nutritional and inflammatory statuses. Hence, further investigation into this phenomenon is warranted. Funding: Private Foundation Support