title: 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.
abstract: 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.
authors.affiliation: MidWest Center for Health Services Research and Policy Studies, VA Chicago Healthcare System, Chicago, IL, USA. cbenne@northwestern.edu
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Denis
authors.initials: D
authors.lastname: Cournoyer
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Carson
authors.forename: Jerome
authors.initials: J
authors.lastname: Rossert
authors.forename: Stefano
authors.initials: S
authors.lastname: Luminari
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Steven M
authors.initials: SM
authors.lastname: Belknap
authors.forename: June M
authors.initials: JM
authors.lastname: McKoy
authors.forename: E Alison
authors.initials: EA
authors.lastname: Lyons
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kim
authors.forename: Rishi
authors.initials: R
authors.lastname: Sharma
authors.forename: Stacey
authors.initials: S
authors.lastname: Costello
authors.forename: Edwin B
authors.initials: EB
authors.lastname: Toffelmire
authors.forename: George A
authors.initials: GA
authors.lastname: Wells
authors.forename: Hans A
authors.initials: HA
authors.lastname: Messner
authors.forename: Paul R
authors.initials: PR
authors.lastname: Yarnold
authors.forename: Steven M
authors.initials: SM
authors.lastname: Trifilio
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Allen
authors.initials: A
authors.lastname: Nissenson
authors.forename: Lay-Cheng
authors.initials: LC
authors.lastname: Lim
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Nicole
authors.initials: N
authors.lastname: Casadevall
mesh_terms: 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
chemical_list: D001323:Autoantibodies; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa