A Randomized Study of Extended Dosing Regimens for Initiation of Epoetin Alfa Treatment for Anemia of Chronic Kidney Disease

Background and objectives: Although epoetin alfa is commonly initiated weekly (QW) in anemic chronic kidney disease (CKD) patients, recent evidence indicates that it can be initiated every 2 wk (Q2W) and used in maintenance therapy every 4 wk (Q4W). This study examined the feasibility of initiating epoetin alfa Q4W in anemic CKD patients not receiving dialysis.Design, setting, participants, & measurements: This open-label study randomized subjects (1:2:2:2) to treatment with epoetin alfa 10,000 IU QW, 20,000 IU Q2W, 20,000 IU Q4W, or 40,000 IU Q4W for 16 wk. Subjects were ≥18 yr, had hemoglobin <11 g/dl, a glomerular filtration rate of 15 to 90 ml/min per 1.73 m², and had not received erythropoietic therapy within 8 wk. The primary analysis was a noninferiority comparison of the 40,000 IU Q4W to the 20,000 IU Q2W group in the per-protocol population with respect to hemoglobin change from baseline to the end of study.Results: Of 262 subjects randomized, 229 comprised the per-protocol population. Mean hemoglobin change from baseline for the 40,000 IU Q4W group (1.24 g/dl) was not inferior to the 20,000 IU Q2W group (1.11 g/dl) with the lower limit of 95% CI, −0.21 g/dl. In the QW, 20,000 IU Q2W, 20,000 IU Q4W, and 40,000 IU Q4W groups, 90%, 87%, 75%, and 86% of subjects, respectively, achieved a hemoglobin increase ≥1 g/dl. Serious adverse events were similar across all groups.Conclusions: Epoetin alfa can be initiated Q4W in anemic CKD subjects.Epoetin alfa, the first commercially available erythropoietic-stimulating agent (ESA), was initially administered three times per week to patients with chronic kidney disease (CKD) and anemia. Today physicians commonly initiate the drug weekly. This may be inconvenient for patients with chronic anemia. In clinical practice, extended dosing regimens may offer advantages for patients and healthcare practitioners in terms of flexibility, improved compliance, and reduced costs (1). To allow for longer dosing intervals, newer ESAs have been developed with longer serum half-lives. There is now increasing evidence that epoetin alfa, despite its relatively short serum half-life, can be administered at extended dosing intervals. Epoetin alfa regimens of up to every 4 wk (Q4W) have been shown to be effective in maintaining hemoglobin (Hb) concentrations ≥11 g/dl in patients with CKD (2–4). Recently, a study demonstrated that epoetin alfa could be effectively initiated every 2 wk (Q2W) (5). The primary objective of this study was to explore the feasibility of initiating therapy with epoetin alfa at dosing intervals of up to Q4W in subjects with anemia of CKD not receiving dialysis.