Comparative Crossover Study of Intravenously and Subcutaneously Administered Recombinant Human Erythropoietin in Hemodialysis Patients

Abstract

A comparative crossover study of intravenously (i.v.) and subcutaneously (s.c.) administered recombinant human erythropoietin (r-HuEPO) was conducted in 20 patients with end-stage renal disease on maintenance hemodialysis. The patients were randomized into two groups. Group 1 received r-HuEPO i.v. thrice weekly and group II r-HuEPO s.c. twice weekly for 12 weeks, then the therapy was crossed over for another 12-week period. The initial dose was 50 U/kg/i.v. dose and 40 U/kg/s.c. dose. In all but 1 patient an adequate hematologic response was obtained. In group 1 the mean hemoglobin (Hb) level increased from 4.8 (Hbo) to 6.0 after 12 weeks (HbΠ) and further to 6.5 mmol/l after 24 weeks (Hb24) throughout the study (0.025 < p < 0.05). In group II it increased from 4.6 (Hb₀) to 7.1 (Hbι₂) to 6.9 mmol/l (Hb₂₄) (0.01 < p < 0.025). There was a significant difference between the two groups (p < 0.05). The rise in Hb in group II during the first 12 weeks of the study was achieved by only half the cumulative dose of r-HuEPO (11,820 U) per kilogram compared to the consumption in group I (24,575 U). In the last 12 weeks of the study the requirement of r-HuEPO to maintain Hb level was equal in the two groups. In group I serum erythropoietin (EPO) level increased slowly throughout the study. In group II an increment was followed by a decrease beyond prestudy level. This happened at an erythropoietic response with mean hematocrit (Hct) about 35%. In group I a mean Hct > 35% was never reached. This might indicate the existence of an EPO-Hct feedback mechanism. In conclusion, s.c. administration is significantly more effective than i.v. administration as induction therapy, requiring only half the dose of r-HuEPO. Also it can be administered twice weekly, and a start dose of 40 U/kg/dose is suggested aiming at a Hct not exceeding 35%.

Erythropoietin-Alpha Dosage Requirements in a Provincial Hemodialysis Population: Effect of Switching from Subcutaneous to Intravenous Administration

“…Only 4 studies included in the meta-analysis incorporated designs where patients were converted from s.c. to i.v. erythropoietin, consistent with our design [17,18,19,20]. Two of these studies failed to demonstrate any significant differences between s.c. and i.v.…”

Subcutaneous Compared with Intravenous Epoetin in Patients Receiving Hemodialysis

“…Many, [12][13][14][15][16][17][18][19][20][21] but not all, [22][23][24][25][26][27] previous trials also concluded that the doses of epoetin required to maintain the hematocrit at a given level were lower with a subcutaneous route of administration, but most of those studies were nonrandomized crossover studies in which the patients were switched from the intravenous to the subcutaneous route of administration. This design does not take into consideration the possibility of crossover effects that would, owing to the long half-life of red cells, delay the decrease in hematocrit resulting from an inadequate dose.…”