Nephrol Dial Transplant (2004) 19: 1330-1331
Nephrol Dial Transplant Vol. 19 No. 5 © ERA-EDTA 2004; all rights reserved
Once-weekly erythropoietic therapy: is there a difference between the available preparations?
Sir,
Iain Macdougall provided, in general, a comprehensive review of once-weekly administrations of epoetin 
, epoetin ß and darbepoetin [1]. However, additional mention could have been made of the differences between epoetin and epoetin ß, as well as further analysis of the data from studies of subcutaneous (s.c.) administration.
With regard to the differences between epoetin and epoetin ß, as the article highlights, the validity of once-weekly administration has only been established in large-scale, randomized controlled trials of epoetin ß administration [2,3]. Comparable data are not yet available for epoetin . The results reported by the Swedish Study Group [3] and Locatelli et al. [2] showed that once-weekly epoetin ß is an effective regimen in haemodialysis patients in the maintenance phase of treatment. In the Swedish study, the epoetin ß dose and haemoglobin level remained stable during the 24-week study, with no statistically significant differences between the groups in change from week 0 to week 24 [3]. The study reported by Locatelli et al. [2] used rigorous and validated statistical methods to show that once-weekly and three-times-weekly s.c. epoetin ß administrations are clinically and statistically equivalent. As Macdougall points out, the patients included in these studies were iron replete and well dialysed. However, these inclusion criteria should be regarded as standard in trials of dialysis patients; indeed, they were also adhered to in the two darbepoetin dialysis studies recently published in full [4,5]. Furthermore, a survey conducted in 2002 of over 2000 haemodialysis patients (
85% of Sweden's haemodialysis population) showed that 95% had a Kt/V of >1.0 and 92% and 80% had serum ferritin above 100 and 200 µg/l, respectively (unpublished data, Swedish Society of Nephrology); these values are also in line with current recommendations [6]. Therefore, contrary to Macdougall's remark about a highly selected, well-dialysed and iron-replete population, the inclusion criteria in the epoetin ß trials can be considered representative of the haemodialysis population encountered in clinical practice.
The article also describes results from uncontrolled studies of once-weekly epoetin administration which indicated lack of efficacy. However, patients in the study reported by Jones et al. [7] received both epoetin and epoetin ß. Use of both epoetin products may have contributed to the discrepancy between these results and those reported in the epoetin ß randomized trials. This hypothesis is supported by reported differences in the pharmacological properties of epoetin and epoetin ß [8].
Further analysis of data from studies of s.c. administration and its advantages over the intravenous (i.v.) route could also have been provided. For example, with regard to the evaluation of pharmacokinetic profiles, the article only compares the half-lives of i.v. darbepoetin and i.v. epoetin (25.3 and 8.5 h, respectively). A comparison should also be made with s.c. epoetin; the reported half-lives of s.c. epoetin and s.c. epoetin ß are 19.4 and 24.2 h, respectively [8].
In addition, s.c. administration gives patients the option to self-administer erythropoietic treatment, and s.c. epoetin has been shown to be more cost-effective than i.v. epoetin [9]. Moreover, in comparison with the i.v. route, s.c. administration may be associated with reduced incidences of erythropoietin-associated hypertension [10]. These benefits, as well as the differences in epoetin and epoetin ß clinical profiles, should be taken into account in an evaluation of erythropoietic therapy.
Conflict of interest statement: I have been involved with clinical trials for Amgen, the makers of darbepoetin (Aranesp®); Johnson and Johnson, the makers of epoetin (Eprex®); and F. Hoffmann-La Roche, the makers of epoetin ß (NeoRecormon®).
Department of Nephrology Centralsjukhuset Karlstad Sweden Email: lars.weiss{at}liv.se
References
- Macdougall IC. Once-weekly erythropoietic therapy: is there a difference between the available preparations? Nephrol Dial Transplant 2002; 17: 2047–2051
[Free Full Text] - Locatelli F, Baldamus CA, Villa G, Ganea A, Martin de Francisco AL. Once-weekly compared with three-times-weekly subcutaneous epoetin ß: results from a randomized, multicenter, therapeutic-equivalence study. Am J Kidney Dis 2002; 40: 119–125[Medline]
- Weiss LG, Clyne N, Divino Fihlho J, Frisenette-Fich C, Kurkus J, Svensson B on behalf of the Swedish Study Group. The efficacy of once weekly compared with two or three times weekly subcutaneous epoetin ß: results from a randomized controlled multicentre trial. Nephrol Dial Transplant 2000; 15: 2014–2019
[Abstract/Free Full Text] - Nissenson AR, Swan SK, Lindberg JS et al. Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kidney Dis 2002; 40: 110–118[CrossRef][Web of Science][Medline]
- Vanrenterghem Y, Bárány P, Mann JF et al. Randomized trial of darbepoetin alfa treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients. Kidney Int 2002; 62: 2167–2175[CrossRef][Web of Science][Medline]
- European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure. Nephrol Dial Transplant 1999; 14 [Suppl 5]: 1–50[Medline]
- Jones CH, Ridley L, Richardson D. Which EPO dose per week? Nephrol Dial Transplant 2002; 17: 1855
[Free Full Text] - Halstenson CE, Macres M, Katz SA et al. Comparative pharmacokinetics and pharmacodynamics of epoetin alfa and epoetin beta. Clin Pharmacol Ther 1991; 50: 702–712[Web of Science][Medline]
- Besarab A, Reyes CM, Hornberger J. Meta-analysis of subcutaneous versus intravenous epoetin in maintenance treatment of anemia in hemodialysis patients. Am J Kidney Dis 2002; 40: 439–446[Medline]
- Navarro JF, Teruel JL, Marcén R Ortuño J. Improvement of erythropoietin-induced hypertension in hemodialysis patients changing the administration route. Scan J Urol Nephrol 1995; 29: 11–14[Medline]
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