Nephrol Dial Transplant (2004) 19: 1331
Nephrol Dial Transplant Vol. 19 No. 5 © ERA-EDTA 2004; all rights reserved
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Sir,I would like to thank Lars Weiss for his interesting comments regarding my Editorial Comment [1] from over a year ago! However, I do have some difficulty accepting one or two of his arguments. While one cannot completely exclude the possibility of different pharmacodynamics between epoetin alfa and epoetin beta, I feel it is unlikely that a difference in intravenous (i.v.) half-life of 6.8±2.7 h for i.v. epoetin alfa and 8.8±2.2 h for i.v. epoetin beta, along with 19.4±10.7 h for subcutaneous (s.c.) epoetin alfa and 24.2±11.2 h for s.c. epoetin beta [2] can really make a substantial difference to biological activity. There may be other differences between epoetin alfa and epoetin beta previously unrecognized, but it would be surprising if such subtle differences in pharmacokinetics in a study conducted in healthy volunteers translated into an enhanced clinical efficacy.
However, I do accept completely Weiss's comment that inclusion criteria including only iron-replete and well-dialysed patients should be ‘regarded as standard in trials of dialysis patients’. As I said in my Editorial Comment [1], and in a follow-up Reply Letter [3], it is always difficult to extrapolate results from scientific studies into everyday clinical practice. While one cannot criticize the inclusion criteria in either the Swedish [4] or Italian [5] studies, the experience of Jones et al. [6] and Geddes and Woo [7] testify to this. I also disagree with Weiss's comment that a Kt/V of >1 and a ferritin level of >200 µg/l are the ‘norm’ in dialysis units; I accept the unpublished data from the Swedish Society of Nephrology, but it is well known that Sweden boasts some of the best results in renal anaemia management in Europe (as reported in the ESAM survey [8]), and the experience in other countries in Europe falls far short of the results that Weiss quotes. Thus, I still feel that we should be cautious about extrapolating results from well-controlled clinical trials into everyday clinical practice in our dialysis units.
Finally, although half-lives aren’t everything, before getting too excited about a possible difference between 19.4 and 24.2 h for s.c. administration of epoetin alfa and epoetin beta, respectively, one should not forget that the half-life for s.c. darbepoetin alfa is substantially greater at 48.8±12.7 h [9].
Conflict of interest statement. I have received honoraria, travel grants and research funds from Amgen, Ortho Biotech and Roche Pharmaceuticals.
Department of Renal Medicine King's College Hospital London UK Email: Iainc.Macdougall{at}virgin.net
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] - 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]
- Macdougall IC. Once-weekly administration of erythropoietin. Nephrol Dial Transplant 2003; 18: 1415
[Free Full Text] - 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 randomised controlled multicentre trial. Nephrol Dial Transplant 2000; 15: 2014–2019
[Abstract/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 randomised, multicenter, therapeutic-equivalence study. Am J Kidney Dis 2002; 40: 119–125[Medline]
- Jones CH, Ridley L, Richardson D. Which EPO dose per week? Nephrol Dial Transplant 2002; 17: 1855
[Free Full Text] - Geddes CC, Woo YM. Once weekly administration of erythropoietin. Nephrol Dial Transplant 2003; 18: 1415
[Free Full Text] - European Survey on Anaemia Management (EASM). Nephrol Dial Transplant 2000; 15 [Suppl 4]: 1–76
- Macdougall IC, Gray SJ, Elston O et al. Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. J Am Soc Nephrol 1999; 10: 2392–2395
[Abstract/Free Full Text]
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