Received December 21, 2007
Accepted on February 24, 2008

ORIGINAL ARTICLES

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

Bruce Spinowitz ^*1, Michael Germain , Robert Benz , Marsha Wolfson , Tracy McGowan , K. Linda Tang , Marc Kamin , and for the Epoetin Alfa Extended Dosing Study Group

*New York Hospital Queens, Flushing, New York; Western New England Renal & Transplant Associates, Inc, Springfield, Massachusetts; Division of Nephrology, Lankenau Hospital & Lankenau Institute for Medical Research, Wynnewood, Pennsylvania; and Ortho Biotech Clinical Affairs, LLC, Bridgewater, New Jersey

¹ To whom correspondence should be addressed. E-mail: bss9001{at}nyp.org.

	Abstract

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.