Pure red-cell aplasia and epoetin therapy.
BACKGROUND
Between 1988 and 1998, antibody-associated pure red-cell aplasia was reported in three patients who had undergone treatment with recombinant human erythropoietin (epoetin). Between 1998 and 2000, 13 such cases were reported from France--12 in patients who had received the Eprex formulation of epoetin alfa and 1 in a patient who had received Neorecormon (a formulation of epoetin beta); both are products that are marketed outside the United States.


METHODS
We obtained reports of epoetin-associated pure red-cell aplasia from the Food and Drug Administration and from the manufacturers of Eprex, Epogen (another formulation of epoetin alfa), and Neorecormon. The numbers of case reports and estimates of exposure-adjusted incidence were analyzed according to the product, the cause of anemia, the route of administration, the country in which pure red-cell aplasia was identified, and the date on which pure red-cell aplasia was reported.


RESULTS
Between January 1998 and April 2004, 175 cases of epoetin-associated pure red-cell aplasia were reported for Eprex, 11 cases for Neorecormon, and 5 cases for Epogen. Over half these cases had occurred in France, Canada, the United Kingdom, and Spain. Between 2001 and 2003, the estimated exposure-adjusted incidence was 18 cases per 100,000 patient-years for the Eprex formulation without human serum albumin, 6 per 100,000 patient-years for the Eprex formulation with human serum albumin, 1 case per 100,000 patient-years for Neorecormon, and 0.2 case per 100,000 patient-years for Epogen. After procedures were adopted to ensure appropriate storage, handling, and administration of Eprex to patients with chronic kidney disease, the exposure-adjusted incidence decreased by 83 percent worldwide.


CONCLUSIONS
After the peak incidence of Eprex-associated pure red-cell aplasia was reached in 2001, interventions designed in response to drug-monitoring programs worldwide resulted in a reduction of more than 80 percent in the incidence of pure red-cell aplasia due to Eprex.
Midwest Center for Health Services Research and Policy Studies, Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60611, USA. cbenne@northwestern.edu
Charles L
CL
Bennett
Stefano
S
Luminari
Allen R
AR
Nissenson
Martin S
MS
Tallman
Stephen A
SA
Klinge
Norene
N
McWilliams
June M
JM
McKoy
Benjamin
B
Kim
E Allison
EA
Lyons
Steve M
SM
Trifilio
Dennis W
DW
Raisch
Andrew M
AM
Evens
Timothy M
TM
Kuzel
Glen T
GT
Schumock
Steven M
SM
Belknap
Francesco
F
Locatelli
Jerôme
J
Rossert
Nicole
N
Casadevall
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012010:Red-Cell Aplasia, Pure / Q000139:chemically induced* / Q000453:epidemiology
D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D000068817:Epoetin Alfa