Subcutaneous erythropoietin therapy: efficacy and economic implications

Recent studies have suggested that lower doses of erythropoietin (rHuEPO) may be required to achieve a target hematocrit when the hormone is administered subcutaneously compared with intravenously. In this article, previous studies are reviewed with a focus on the recently completed Department of Veterans Affairs multicenter trial comparing the two routes of administration. In this randomized, parallel group study of 208 patients, the average rHuEPO dose required to maintain a target hematocrit of 30% to 33% for 26 weeks was 95.1 +/- 75.0 U/kg/wk in the subcutaneous-therapy group and 140.3 +/- 88.5 U/kg/wk in the intravenous-therapy group (P < 0.0001). The specific mechanisms that result in the greater efficiency of the subcutaneous route are unknown but are probably related to the prolonged half-life of the hormone with subcutaneous administration. Possible mechanisms resulting in greater efficiency with subcutaneous therapy include sustained stimulation of the erythroid progenitor cells, diminished inhibition of erythropoiesis by proinflammatory cytokines, and prevention of neocytolysis, the hemolysis of newly formed red blood cells. Because most hemodialysis patients in the United States are receiving rHuEPO by the intravenous route, switching to the subcutaneous route may result in significant cost savings for the health care system.