Long-term outcome of individuals with pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant epoetin: a follow-up report from the Research on Adverse Drug Events and Reports (RADAR) Project.
Since its introduction in 1988, recombinant human erythropoietin (epoetin) has been standard treatment for patients with anemia due to chronic kidney disease. From 1998 to 2004, nearly 200 epoetin-treated persons with chronic kidney disease developed antibodies to epoetin, resulting in pure red cell aplasia (PRCA). The majority of these patients received Eprex, an epoetin alfa product marketed exclusively outside the United States. Herein, we report on the long-term outcome of these individuals. For 170 chronic kidney disease patients who developed epoetin-associated PRCA and had 3 months or more follow-up information available, case reports from the Food and Drug Administration and epoetin manufacturers were reviewed for information on clinical characteristics of the patients, immunosuppressive treatments, epoetin responsiveness, and hematologic recovery. Overall, 64% of the PRCA patients received immunosuppressive therapy, including 19 who also underwent a renal transplantation. Thirty-seven percent experienced a hematologic recovery, with higher hematologic recovery rates among PRCA patients who received immunosuppressive therapy (57% vs 2%, P < .001). Among 34 patients who received epoetin after the onset of PRCA, 56% regained epoetin responsiveness. The highest rates of epoetin responsiveness were observed among persons whose antierythropoietin antibodies were undetectable when epoetin was administered (89%). Among chronic kidney disease patients with epoetin-associated PRCA, epoetin discontinuation and immunosuppressive therapy or renal transplantation is necessary for hematologic recovery. Reinitiation of epoetin therapy among individuals could be considered if antierythropoietin antibodies are undetectable.
Bennett
Charles L
CL
MidWest Center for Health Services Research and Policy Studies, VA Chicago Healthcare System, Chicago, IL, USA. cbenne@northwestern.edu
Cournoyer
Denis
D
Carson
Kenneth R
KR
Rossert
Jerome
J
Luminari
Stefano
S
Evens
Andrew M
AM
Locatelli
Francesco
F
Belknap
Steven M
SM
McKoy
June M
JM
Lyons
E Alison
EA
Kim
Benjamin
B
Sharma
Rishi
R
Costello
Stacey
S
Toffelmire
Edwin B
EB
Wells
George A
GA
Messner
Hans A
HA
Yarnold
Paul R
PR
Trifilio
Steven M
SM
Raisch
Dennis W
DW
Kuzel
Timothy M
TM
Nissenson
Allen
A
Lim
Lay-Cheng
LC
Tallman
Martin S
MS
Casadevall
Nicole
N
D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002908:Chronic Disease; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006397:Hematinics / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007674:Kidney Diseases / Q000276:immunology / Q000628:therapy*; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D011994:Recombinant Proteins; D012010:Red-Cell Aplasia, Pure / Q000097:blood / Q000139:chemically induced / Q000628:therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
D001323:Autoantibodies; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa