Recombinant human erythropoietin (epoetin) has been shown to be an effective and well-tolerated treatment for patients with anemia, and helps them achieve recommended hemoglobin (Hb) levels (>11 g/dL). However, due to safety concerns related to higher Hb levels, the National Kidney Foundation/Kidney Disease Outcomes Quality Initiative recently recommended Hb target levels between 11 and 12 g/dL, a range which as been clinically difficult to achieve and maintain in many patients. Furthermore, subcutaneous (SC) epoetin alfa was recently associated with a marked increase in anemic patients who developed pure red cell aplasia (PRCA). These developments have lead researchers to focus on epoetin beta as an alternative treatment, and therefore, the Gain effectiveness in Anemia treatment with NeoRecormon (GAIN) study was designed to examine the clinical benefits of switching from SC or intravenous epoetin alfa to SC epoetin beta.

The study population included 4,264 anemic patients aged 18 years or older who had been treated with any erythropoiesis-stimulating agent (ESA) for at least 12 weeks. After the treatment period, patients underwent an 18-month observational period in which they were recommended treatment with SC epoetin beta. The study’s primary objective was to assess the effectiveness of SC epoetin beta treatment in achieving Hb stability and to compare this management across a number of European countries. Overall, the number of patients within recommended Hb target levels maintained those levels with SC epoetin beta, even after switching from a different ESA. In fact, there was a slight increase in the number of patients who achieved target levels at months 7-12, as well as a slight decrease in the proportion of patients with an Hb level <10 g/dL. Furthermore, 97% of patients experienced good tolerability for SC epoetin beta, with no cases of PRCA reported.

These findings suggest that switching to SC epoetin beta is a safe and effective treatment method. This switch also resulted in a dose savings of 24%, and the once-weekly dosing schedule provided a low-cost alternative to more frequent dosing strategies. Importantly, slight variation in each country’s results suggests that guideline adherence differs, and that existing country-specific factors will be key to developing standard guidelines across the continent. Finally, since the study was open label and observational, more trials are needed to determine if other factors – such as concomitant iron therapy – contributed to the stability of target Hb levels.

Rath T, Mactier RA, Weinreich T, Scherhag AW; GAIN Investigators. Effectiveness and safety of recombinant human erythropoietin beta in maintaining common haemoglobin targets in routine clinical practice in Europe: the GAIN study. Curr Med Res Opin. 2009 Apr;25(4):961-70.

NAAC Expert Commentary:
The observational study by Rath et al, investigating the use of SC epoetin beta as an alternative to epoetin alfa for treatment of anemic patients on hemodialysis in Europe, provided further support for the use of SC epoetin beta in patients on hemodialysis and was well tolerated in CKD or patients on forms of Renal Replacement Therapy (RRT).

This study suggests hemodialysis patients on SC epoetin beta dosing maintained Hb values within target Hb range (10-12 g/dL) and varying not more than ±1 g/dL during the 18-month observational period. Maintaining target range hemoglobin levels was achieved by using significantly lower doses of epoetin beta subcutaneously in comparison to IV dosing. This success was roughly comparable with ESA treatment effectiveness prior to the study. However, it is important to recognize the role concomitant iron therapy may have played in this study to contribute to the stability of target Hb levels. The use of epoetin beta in hemodialysis patients also merits considerable attention for practitioners in the United States where dosing schedules and cost effectiveness have become important considerations for anemia treatment with ESAs.

As also mentioned by the authors, differences in protocol among the participating countries introduces many variables which could have affected the results and which may play an important role in standardizing care within Europe.

Last Updated: May 15, 2009