Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial.
BACKGROUND
Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly.


METHODS
Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11-13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and darbepoetin alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50-53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953.


RESULTS
Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with darbepoetin alfa met the response definition (64.1% and 40.4%; P < 0.0001). Doses increased by 6.8% with methoxy polyethylene glycol-epoetin beta and 58.8% with darbepoetin alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups.


CONCLUSIONS
Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than darbepoetin alfa at once-monthly dosing intervals despite dose increases with darbepoetin alfa.
Eurodial, Dialysis Unit, Leiria, Portugal. fcarrera@mail.telepac.pt
Fernando
F
Carrera
Charmaine E
CE
Lok
Angel
A
de Francisco
Francesco
F
Locatelli
Johannes F E
JF
Mann
Bernard
B
Canaud
Peter G
PG
Kerr
Iain C
IC
Macdougall
Anatole
A
Besarab
Giuseppe
G
Villa
Isabelle
I
Kazes
Bruno
B
Van Vlem
Shivinder
S
Jolly
Ulrich
U
Beyer
Frank C
FC
Dougherty
D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000209:etiology*; D002908:Chronic Disease; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000627:therapeutic use; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000627:therapeutic use; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D006435:Renal Dialysis; D016896:Treatment Outcome
D004337:Drug Carriers; D006397:Hematinics; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol