Nephrol Dial Transplant (2004) 19: 1940
Nephrol Dial Transplant Vol. 19 No. 7 © ERA-EDTA 2004; all rights reserved
Letter
Comment on letter by Deray
Sir,In his letter, Deray has attempted to identify a single, fixed dose conversion ratio when switching patients from epoetin to darbepoetin alfa therapy and has concluded that this ratio is not the same for the intravenous (i.v.) and subcutaneous (s.c.) routes of administration [1].
In trying to identify single, fixed dose conversion ratios by the s.c. and i.v. routes, Deray has compared the results from a European study in epoetin-naïve pre-dialysis patients [2] with a US study in haemodialysis patients receiving prior stable epoetin therapy [3]. As neither of these studies was designed to investigate conversion methodologies and as they involve different patient populations and routes of administration, it is misleading to draw conclusions from them about conversion ratios.
Furthermore, as has been pointed out previously [4,5], the implementation of a single, fixed dose ratio to convert patients from epoetin to darbepoetin alfa is not appropriate for either the i.v. or s.c. routes of administration, as the relationship between epoetin and darbepoetin alfa doses is non-linear. As well as being influenced by prior epoetin dose, the conversion ratio will also be influenced by other factors such as dosing interval. This is why the European prescribing information for darbepoetin alfa suggests 200:1 as an initial conversion ratio (based on equivalent peptide mass) but notes that ‘titration to optimal therapeutic doses is expected for individual patients’. In the two studies cited by Deray, 42 [2] and 69% [3] of patients required further dose titration after starting darbepoetin alfa. In the first study, the patients had been naïve to all epoetin-related therapies, prior to starting darbepoetin alfa. In the second study, patients were switched from epoetin to darbepoetin alfa therapy.
It is therefore incorrect to speculate, on the basis of single conversion ratios calculated from mean data from dissimilar studies, that switching from SC epoetin to darbepoetin alfa would necessitate a dose increase of 20–30%. As I stated in my original article [6], formal head-to-head studies are required before any definite conclusions can be made about the relative cost–benefit of these two therapies.
Lastly, Deray cites an abstract by Hörl [7] to support his contention that switching from darbepoetin alfa once every 2 weeks to a 3-week dosing schedule necessitates a 13% increase in dose. However, this abstract does not make any mention about 3-week dosing, so it is difficult to understand how he reached this conclusion. Studies in dialysis patients have shown that there is no dose penalty associated with changing from darbepoetin alfa dosing once every 2 weeks to once every 3 weeks [8] and, likewise, only a 0–2.2% increase in total weekly dose was necessary when changing to dosing once every 4 weeks [8,9]. Again, more controlled studies are required to examine the true cost-effectiveness of darbepoetin alfa dosing less frequently than once per week.
I completely agree with Deray in that attempts to reduce the total cost of anaemia therapy are of the utmost importance to allow more patients to benefit. Pending further studies, and for this reason, treatment should be individualized to each patient's particular requirements, rather than by indiscriminately applying arbitrary dosing algorithms.
Conflict of interest statement. I. C. Macdougall has received honoraria, travel grants and research funds from Amgen, Ortho Biotech and Roche Pharmaceuticals.
Renal Unit King's College Hospital London, UK Email: iainc.macdougall{at}virgin.net
References
- Deray G. Once-weekly erythropoietic therapy: is there a difference between the available preparations? Nephrol Dial Transplant 2003; 18: 2455–2456
[Free Full Text] - 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][Web of Science][Medline]
- 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]
- Scott SD. Dose conversion from recombinant human erythropoietin to darbepoetin alfa: recommendations from clinical studies. Pharmacotherapy 2002; 22: 160S–165S[CrossRef][Web of Science][Medline]
- Nissenson AR. Dosing darbepoetin alfa continued. Am J Kidney Dis 2003; 41: 1334–1336[Medline]
- Macdougall IC. Once-weekly erythropoietic therapy; is there a difference between the available preparations? Nephrol Dial Transplant 2002; 17: 2047–2051
[Free Full Text] - Hörl W. IV darbepoetin alfa is more effective than IV rHu-Epo in maintaining target Hb concentrations in patients with renal anemia. Nephrol Dial Transplant 2002; 17 [Suppl 1]: 24
- Walker R et al. Aranesp® (Darbepoetin alfa) administered at reduced frequencies of once every three weeks (Q3W) and once every four weeks (Q4W) maintains hemoglobin levels in patients with chronic kidney disease (CKD) receiving dialysis. Presented at the National Kidney Foundation Clinical Nephrology Meeting, April 17–21, 2002, Chicago, IL
- Walczyk M, Agarwal A, Ling B et al. Aranesp® (Darbepoetin alfa) administered once monthly maintains hemoglobin levels in patients with chronic kidney disease (CKD). Presented at the National Kidney Foundation annual meeting, April 2–6, 2003, Dallas, TX
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