Epoetin-associated pure red cell aplasia: past, present, and future considerations.
BACKGROUND
Since 1988, millions of patients have received epoetin products intravenously (IV) and subcutaneously. In 1998, epoetin-associated pure red cell aplasia (PRCA) was first reported and causation was attributed to formulations without human serum albumin (HSA), subcutaneous administration, and uncoated rubber stoppers.


METHODS
Data on erythropoietin (EPO)-associated PRCA were obtained from the Food and Drug Administration (FDA), regulatory authorities in other countries, and the manufacturers of epoetin alfa, epoetin beta, and darbepoetin. The data included information on numbers of PRCA cases and estimated exposure-adjusted incidence rates by EPO product, anemia etiology, administration route, country of PRCA identification, and date reported.


RESULTS
In 1999, academicians in Paris identified 12 EPO-treated patients with antibody-mediated PRCA; 11 of these patients were on hemodialysis and had received subcutaneous Eprex (Johnson & Johnson). In 2002, authorities in Europe, Australia, Singapore, and Canada mandated Eprex by IV route to hemodialysis patients, and the relevant manufacturers added Teflon coating to prefilled syringes of Eprex; PRCA cases subsequently decreased by 90 percent. By 2003, 180 Eprex-associated PRCA cases were identified in Europe, Canada, Australia, and Asia, despite improvements in handling. Since 2002, FDA safety databases include information on 59 new cases of antibody-associated PRCA, primarily associated with subcutaneous epoetin alfa and darbepoetin that does not contain HSA.


CONCLUSIONS
Independent actions by regulatory authorities, manufacturers, and academic researchers identified significant numbers of PRCA cases between 1998 and 2003 and characterized the probable etiology. Today, antibody-mediated PRCA is an infrequent class toxicity occurring among some hemodialysis patients on EPOs.
McKoy
June M
JM
Division of Hematology/Oncology and Geriatric Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. jmmckoy@aol.com
Stonecash
Robin E
RE
Cournoyer
Denis
D
Rossert
Jerome
J
Nissenson
Allen R
AR
Raisch
Dennis W
DW
Casadevall
Nicole
N
Bennett
Charles L
CL
D000740:Anemia / Q000188:drug therapy* / Q000453:epidemiology; D004348:Drug Labeling; D064420:Drug-Related Side Effects and Adverse Reactions; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects*; D006397:Hematinics / Q000009:adverse effects*; D006801:Humans; D011994:Recombinant Proteins; D012010:Red-Cell Aplasia, Pure / Q000139:chemically induced* / Q000453:epidemiology
D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa