Once-Weekly Epoetin Alfa Dosing Is as Effective as Three Times–Weekly Dosing in Increasing Hemoglobin Levels and Is Associated With Improved Quality of Life in Anemic HIV-Infected Patients

Abstract

QW dosing of epoetin alfa is as effective as TIW dosing in increasing Hb levels, which was associated with improved QOL in anemic HIV-positive patients. QW dosing should also offer added convenience for patients and caregivers.

Cytoprotective doses of erythropoietin or carbamylated erythropoietin have markedly different procoagulant and vasoactive activities

“…Although the increased BP often parallels the rise in hematocrit, studies in both iron-deficient rodents (32) and humans (33) have conclusively demonstrated that these two events are not causally linked and that rhEPO acts directly on the vasculature. To determine whether the pressor action of rhEPO is mediated through the hematopoietic (EPOR) 2 or the tissue-protective EPOR-␤c receptor, we treated rats with rhEPO or CEPO while monitoring systolic BP plethysmographically via tail cuff. Chronic administration of rhEPO at either low (1.2 g͞kg of bw twice weekly) or high (40 g͞kg of bw three times weekly) doses was associated with significant and comparable increases in systolic BP of 12 Ϯ 3% (low dose) and 5 Ϯ 2% (high dose) of baseline (118 Ϯ 6.1 mmHg; 1 mmHg ϭ 133 Pa), respectively (P Ͻ 0.05 vs. saline and P Ͻ 0.01 vs. CEPO).…”

“…Subsequent work has identified an additional receptor comprised of the EPOR and the ␤c receptor (CD131) subunit, the latter also used for granulocyte͞macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-5 signaling (29). CEPO is therefore a useful ligand to distinguish between effects mediated by the hematopoietic (EPOR) 2 and cytoprotective EPOR-␤c receptors. The data described here, obtained after doses reasonably anticipated for future study of tissue protection in humans, suggest that stimulation of human multipotent hematopoietic colonies and rat platelets, as well as E-and P-selectin (and possibly PAI-1) up-regulation are mediated by the (EPOR) 2 receptor.…”

“…Even though peak hematopoietic effects of rhEPO are reached at a dose of 300 units͞kg of body weight (bw) administered intravenously (i.v.) (1), larger doses have been used recently in an effort to reduce the frequency of administration (2) or in an attempt to treat refractory anemia (3). Notably, several clinical trials evaluating the use of rhEPO in anemic patients with breast (4,5) or head and neck (6) malignancies have raised concerns because of lower survival within the rhEPO treatment arms.…”

“…Further, tissue-protective and nonerythropoi-etic molecules have been developed that signal via EPOR-␤c and not (EPOR) 2 (30). For example, carbamylated rhEPO (CEPO) has no affinity for (EPOR) 2 and is, therefore, nonerythropoietic and yet maintains full tissue-protective activity (30).…”

“…For example, carbamylated rhEPO (CEPO) has no affinity for (EPOR) 2 and is, therefore, nonerythropoietic and yet maintains full tissue-protective activity (30). Thus, biological activities possessed by rhEPO, but not by CEPO, functionally define the effects of (EPOR) 2 . These discoveries provide the conceptual framework and tools with which to assess the relative contributions of each receptor isoform to the AEs of rhEPO.…”