Once-weekly erythropoietic therapy: is there a difference between the available preparations?

Gilbert Deray

Department of Nephrology Hospital Pitié–Salpêtrière Paris France Email: gilbert.deray{at}psl.ap-hop-paris.fr

Sir,

I read with interest Macdougall’s article [1]. However, I disagree with some of his statements. The 200 IU conversion factor between epoetin and darbepoetin has not been clearly validated. In the editorial, Macdougall suggests, based on an uncontrolled, unpublished study, that the conversion factor might be higher (238:1 after 4 months) than anticipated and commonly admitted (200), suggesting that the use of darbepoetin may reduce treatment cost.

Locatelli et al. [2] have compared, in a randomized open-label study, the efficacy of darbepoetin (NESP) with that of rHu-Epo in 166 rHu-Epo-naïve patients. NESP and rHu-Epo were administered subcutaneously for up to 24 weeks. Starting weekly doses were 0.45 µg/kg and 100 IU/kg for NESP and rHu-Epo, respectively (conversion factor: 222.22 IU epoetin for 1 µg darbepoetin alfa). However, at week 24, median study drug doses had decreased to 0.34 µg/kg and 56.9 U/kg for NESP and rHu-Epo, respectively (conversion factor: 167.35 IU epoetin for 1 µg darbepoetin alfa).

Furthermore, Nissenson et al. [3] compared the efficacy of darbepoetin alfa and epoetin alfa in haemodialysis patients in a randomized, double blind, non-inferiority study. Patients receiving epoetin therapy were randomized to continue with epoetin administered i.v. three times weekly or to change to darbepoetin alfa administered i.v. once weekly. The initial dose of darbepoetin alfa was based on a formula equating the protein mass of the two molecules (200 IU epoetin = 1 µg NESP). As quoted by the authors, ‘mean doses of study drugs were similar between baseline and the evaluation period in this study, thus suggesting that the initial protein was appropriate to identify a therapeutic starting dose for patients treated intravenously’.

These data demonstrate that the 200 IU conversion factor is probably appropriate for the i.v. route. However, patients treated subcutaneously with rHu-Epo and one switching to NESP (either i.v. or s.c.) will need a 20–30% increase in epoetin dosage compared with baseline rHu-Epo dosage. These numbers are in line with the now accepted equivalence between i.v. and s.c. doses of NESP [4] (although never demonstrated in a randomized study) as compared with the clear possibility to decrease doses when switching from the i.v. to the s.c. route with rHu-Epo.

Consequently, I suggest that the conversion factor between darbepoetin and rHu-Epo is not similar for both the i.v. and s.c. routes. Furthermore, when administering NESP on a longer dosing schedule, one might have to increase dosage. For example, switching from a once every 2 weeks to a 3 week dosing schedule necessitates a 13% increase in NESP dosage [5].

As outlined in a recent meta-analysis [6] and an editorial [7], attempts to reduce the total cost of anaemia therapy, thereby allowing more patients to benefit from the same healthcare system, are of utmost importance.

Conflict of interest statement. G. Deray is a consultant for Roche laboratory.

References

  1. Macdougall IC. Once-weekly erythropoietic therapy: is there difference between the available preparations? Nephrol Dial Transplant 2002;17: 2047–2051[Free Full Text]
  2. Locatelli F, Olivares J, Walker R et al. on behalf of the European/Australian NESP 980202 Study Group. Novel erythropoiesis stimulating protein for treatment of anemia in chronic renal insufficiency. Kidney Int 2001;60: 741–747[CrossRef][ISI][Medline]
  3. Nissenson R, 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][ISI][Medline]
  4. Vanrenterghem Y, Barany P, Mann JFE et al. on behalf of the European/Australian NESP 970200 Study Group. Randomized trial of Darbepoetin alfa for treatment of renal anemia at a reduced dose frequency compared with rHuEPO in dialysis patients. Kidney Int 2002;62: 2167–2175[CrossRef][ISI][Medline]
  5. Horl W. IV darbepoetin alfa is more effective than IV rHu-Epo in maintaining target Hb concentrations in patients with renal anemia. J Am Soc Nephrol 2002;17[Abstracts Suppl 1]: 24
  6. Besarab A, Reynes CM, Homberger J. Meta-analysis of subcutaneous versus intravenous epoetin in maintenance treatment of anemia in hemodialysis patients. Am J Kidney Dis 2002;40: 439–446[CrossRef][ISI][Medline]
  7. Levin A. Preaching and practice: evidence-based medicine and the accountability of nephrologists within the health care system. The implications of the findings of the cost-saving potential of subcutaneous versus intravenous epoetin therapy. Am J Kidney Dis 2002;40: 662–663[CrossRef][ISI][Medline]