Once-Every-2-Weeks and Once-Weekly Epoetin Beta Regimens: Equivalency in Hemodialyzed Patients Gabriel Mircescu, MD, PhD, Liliana Gârneat a ˘ , MD, PhD, Alexandru Ciocâlteu, MD, PhD, Ovidiu Golea, MD, PhD, Mirela Gherman-Ca ˘ prioara ˘ , MD, PhD, Dimitrie Caps  a, MD, PhD, Eugen Mot a, MD, PhD, Paul Gusbeth-Tatomir, MD, Adrian Ghenu, MD, Simona Ba ˘ lut a ˘ , MD, Niculae Constantinovici, MD, MSc, and Adrian Constantin Covic, MD, PhD ● Background: Currently, less frequent than once-weekly subcutaneous epoetin administration regimens were shown to be equally effective and safe as once-weekly schedules in stable predialysis and peritoneal dialysis patients. Bioequivalency of once-every-2-weeks and once-weekly subcutaneous administration of the same total dose of epoetin beta for the maintenance phase of anemia treatment in stable iron-replete long-term hemodialysis patients therefore was investigated prospectively. Methods: Two hundred seven stable selected hemodialysis patients without diabetes, acute illness, significant inflammation, malnutrition or hyperparathyroidism adminis- tered once-weekly subcutaneous epoetin beta and preserving stable hemoglobin levels between 10 and 12 g/dL (100 and 120 g/L; difference between maximum and minimum of 3 subsequent levels <2.5 g/dL [<25 g/L]) and optimal iron status for at least 8 weeks before inclusion were enrolled and randomly assigned to subcutaneous administration of the same total dose of epoetin beta either once every 2 weeks (group 2w; n  104) or once weekly (group 1w; n  103) for 24 weeks. Results: Per-protocol analyses (group 1w  102 versus group 2w  101) showed similar hemoglobin levels throughout the assessment period (weeks 13 to 24): mean, 11.38 g/dL; 95% confidence interval (CI), 11.23 to 11.54 versus 11.41 g/dL; 95% CI, 11.22 to 11.58. Mean difference was 0.028 g/dL (95% CI, 0.208 to 0.264) in the prespecified range (0.5 g/dL). Epoetin dose ratio of group 2w to group 1w was 0.94 (95% CI, 0.813 to 1.076), also in the prespecified range of equivalence (0.80 to 1.25). Hemoglobin levels and epoetin doses were stable during the study irrespective of treatment schedule, with no differences between groups at any time. Both schedules were well tolerated. Conclusion: Once-every-2-weeks and once-weekly subcutaneous epoetin beta regimens are equivalent in the maintenance phase of anemia treatment in long-term stable hemodialysis patients without diabetes, with similar safety profiles. Am J Kidney Dis 48:445-455. © 2006 by the National Kidney Foundation, Inc. INDEX WORDS: Erythropoiesis-stimulating agent; dosing frequency; hemodialysis (HD); therapeutic equivalence. C URRENT EUROPEAN Best Practice Guidelines 1,2 and the Kidney Disease Out- comes Quality Initiative Committee in the United States 3 recommend preferential subcutaneous (SC) twice- to thrice-weekly epoetin administra- tion. The SC route significantly decreases epo- etin requirements and therefore costs compared with the intravenous (IV) route. 4-6 In addition, solid evidence shows that once-weekly SC admin- istration of epoetin beta is equally efficient and well tolerated in hemodialysis (HD) patients. 7,8 Clinical studies suggested that effects of epoetin alfa are sustained for more than 1 week, enabling less frequent dosing schedules in predialysis pa- tients with chronic kidney disease (CKD). 9,10 A recent European multicenter study of peritoneal dialysis (PD) patients confirmed that once-every- 2-weeks SC epoetin beta administration is effi- cient and safe in the maintenance phase of ane- mia treatment for PD patients. 11 Thus, the From the “Dr. Carol Davila” Teaching Hospital of Ne- phrology; Nephrology and Dialysis Department, “Sf. Ioan Nou” Clinical Hospital; Dialysis Center, “Fundeni” Clini- cal Institute; Dialysis Center, Army Medical Diagnosis and Treatment Center, Bucharest; Dialysis and Renal Transplan- tation Center, Timis ¸oara County Hospital; Nephrology and Dialysis Clinic, Cluj Clinical County Hospital; Nephrology and Dialysis Clinic, Craiova Clinical County Hospital; Dialysis and Transplantation Center, “Dr. C.I. Parhon” University Hospital, Ias ¸i; and Nephrology and Dialysis Department, Dâmbovit a County Hospital, Romania. Received March 2, 2006; accepted in revised form May 8, 2006. Originally published online as doi:10.1053/j.ajkd.2006.05.030 on August 8, 2006. Support: Laboratory determinations of the parameters of iron status, C-reactive protein, and parathyroid hormone, as well as logistics for the transportation of blood samples to the central laboratory, were supported by F. Hoffmann-La Roche. No other financial support was received by any of the authors. Potential conflicts of interest: None. Address reprint requests to Adrian Constantin Covic, PhD, MD, Professor of Nephrology, Dialysis and Transplan- tation Center, “Dr. C.I. Parhon” University Hospital, Ias ¸i, Romania. E-mail: acovic@xnet.ro © 2006 by the National Kidney Foundation, Inc. 0272-6386/06/4803-0011$32.00/0 doi:10.1053/j.ajkd.2006.05.030 American Journal of Kidney Diseases, Vol 48, No 3 (September), 2006: pp 445-455 445