Anti-erythropoietin antibody-mediated pure red cell aplasia after treatment with recombinant erythropoietin products: recommendations for minimization of risk.
Since 1998, there has been a marked increase in incidence of pure red cell aplasia secondary to development of anti-erythropoietin antibodies (Ab+ PRCA) in patients who have chronic kidney disease (CKD) and receive recombinant erythropoietin. The relationship between incidence of Ab+ PRCA and specific erythropoietin products has not been examined rigorously. Manufacturers provided data regarding exposure to erythropoietin products and incidence of Ab+ PRCA between January 1998 and March 2003 in patients with CKD. Assuming a Poisson distribution, a maximum likelihood estimate for the Poisson rate parameter was calculated for each product. A test for homogeneity of Poisson rates was conducted to compare likelihood estimates between products. Global incidence of Ab+ PRCA was relatively low. Likelihood estimates were not significantly different for Epogen, Procrit, and Aranesp, independent of their formulation or route of administration. Eprex lacking human serum albumin (HSA) and administered subcutaneously was associated with the greatest risk of Ab+ PRCA. HSA-containing Eprex administered subcutaneously was associated with a lower risk than HSA-free Eprex administered subcutaneously, but this risk exceeded that of intravenous Epogen and intravenous HSA-free Eprex. NeoRecormon administered subcutaneously was associated with less risk than subcutaneous HSA-free Eprex but more risk than intravenous Epogen. HSA-free Eprex should not be administered subcutaneously to patients with CKD due to increased risk of Ab+ PRCA. Although the subcutaneous administration of HSA-containing Eprex is riskier than intravenous Epogen and intravenous HSA-free Eprex, and the use of subcutaneous NeoRecormon is riskier than intravenous Epogen, there is currently no evidence that other products are safer.
Department of Medicine, McGill University Health Centre, Montreal, Quebec H3G 1A4, Canada. cournoyerd@muhchem.mcgill.ca
Denis
D
Cournoyer
Edwin B
EB
Toffelmire
George A
GA
Wells
Dwayne L
DL
Barber
Brendan J
BJ
Barrett
Robert
R
Delage
Donna L
DL
Forrest
Raymonde F
RF
Gagnon
Elizabeth A
EA
Harvey
Pierre
P
Laneuville
Bruce J
BJ
Patterson
Man-Chiu
MC
Poon
Gerald A
GA
Posen
Hans A
HA
Messner
D017677:Age Distribution; D001323:Autoantibodies / Q000276:immunology*; D015331:Cohort Studies; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006287:Health Planning Guidelines; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000276:immunology; D008297:Male; D015995:Prevalence; D011322:Primary Prevention; D011994:Recombinant Proteins; D012010:Red-Cell Aplasia, Pure / Q000139:chemically induced* / Q000453:epidemiology*; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution
D001323:Autoantibodies; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa