Darbepoetin alpha in lower-than-equimolar doses maintains haemoglobin levels in stable haemodialysis patients converting from epoetin alpha/beta.
BACKGROUND
The conversion of patients on stable epoetin therapy to darbepoetin alpha is usually carried out according to the '1 microg darbepoetin =200 U epoetin' rule, which is based on the protein content of the two compounds. Since several observations have suggested that this conversion factor leads to an overestimate of the required darbepoetin dose, the present multicentre study was designed to assess the true conversion ratio by prospectively evaluating the change in darbepoetin alpha dose after conversion from epoetin, which was required to keep haemoglobin (Hb) stable.


METHODS
Haemodialysis patients with stable Hb and maintained on either s.c. or i.v. epoetin (alpha or beta) were switched to intravenously administered darbepoetin alpha according to the 1:200 rule. Subjects treated with epoetin two or three times per week received one weekly dose of darbepoetin alpha, subjects on weekly epoetin received darbepoetin alpha every 2 weeks. For 20 weeks, darbepoetin alpha was changed every 2 weeks according to a pre-specified algorithm, if this was needed to keep Hb within +/-1.0 g/dl of each subject's individual baseline. Thereafter, patients entered a 4-week evaluation period.


RESULTS
One hundred ad thirty-two patients in 17 Swiss centres were enrolled and 100 completed the study throughout the evaluation period. While mean Hb was maintained stable between baseline and evaluation period (11.8+/-0.6 g/dl in both), the mean required darbepoetin alpha dose decreased from 34.7+/-2.1 to 26.0+/-1.8 microg (-25%, P<0.0001), yielding a mean final conversion ratio of 1:336. A dose decrease was observed in 56 patients, no dose change in 28 and an increase in 16 patients. Dose reduction strongly depended on baseline epoetin dose: no dose reduction was required for baseline epoetin doses <5000 U/week, whereas a 37% lower mean dose was necessary for baseline doses of 7000-10 000 U/week. The darbepoetin alpha dose reduction did not depend on the previous epoetin type (alpha or beta) or the previous epoetin administration route (i.v. vs s.c.).


CONCLUSIONS
The mean darbepoetin alpha dose needed to keep Hb stable in patients previously treated with epoetin is significantly lower than the equimolar dose. Although the equimolar 1:200 conversion ratio is appropriate for lower epoetin doses (<5000 IU/week), the darbepoetin dose for patients converting from >or=5000 IU of epoetin per week is more likely to follow a 1:250 to 1:350 conversion rule. If pricing is based on the 1:200 rule such as in Switzerland, this may translate into cost savings.
Bock
H Andreas
HA
Division of Nephrology, Kantonsspital, Aarau, Switzerland. andreas.bock@ksa.ch
Hirt-Minkowski
Patricia
P
Brünisholz
Michel
M
Keusch
Gerald
G
Rey
Simone
S
von Albertini
Beat
B
D000368:Aged; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000008:administration & dosage*; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy*; D008297:Male; D011994:Recombinant Proteins; D006435:Renal Dialysis
D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa