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

Charles L. Bennett*, Denis Cournoyer, Kenneth R. Carson, Jerome Rossert, Stefano Luminari, Andrew M. Evens, Francesco Locatelli, Steven M. Belknap, June M. McKoy, E. Alison Lyons, Benjamin Kim, Rishi Sharma, Stacey Costello, Edwin B. Toffelmire, George A. Wells, Hans A. Messner, Paul R. Yarnold, Steven M. Trifilio, Dennis W. Raisch, Timothy M. Kuzel & 4 others Allen Nissenson, Lay Cheng Lim, Martin S. Tallman, Nicole Casadevall

*Corresponding author for this work

Research output: Contribution to journalReview article

69 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3343-3347
Number of pages5
JournalBlood
Volume106
Issue number10
DOIs
StatePublished - Nov 15 2005

Fingerprint

Pure Red-Cell Aplasia
Epoetin Alfa
Immunosuppressive Agents
Drug-Related Side Effects and Adverse Reactions
Cells
Recovery
Antibodies
Chronic Renal Insufficiency
Research
Pharmaceutical Preparations
Patient treatment
Erythropoietin
Kidney Transplantation
Therapeutics
United States Food and Drug Administration
Anemia

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Bennett, Charles L. ; Cournoyer, Denis ; Carson, Kenneth R. ; Rossert, Jerome ; Luminari, Stefano ; Evens, Andrew M. ; Locatelli, Francesco ; Belknap, Steven M. ; McKoy, June M. ; Lyons, E. Alison ; Kim, Benjamin ; Sharma, Rishi ; Costello, Stacey ; Toffelmire, Edwin B. ; Wells, George A. ; Messner, Hans A. ; Yarnold, Paul R. ; Trifilio, Steven M. ; Raisch, Dennis W. ; Kuzel, Timothy M. ; Nissenson, Allen ; Lim, Lay Cheng ; Tallman, Martin S. ; Casadevall, Nicole. / 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. In: Blood. 2005 ; Vol. 106, No. 10. pp. 3343-3347.
@article{36325917cebc48a0b1bd6f21e09b904c,
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.",
author = "Bennett, {Charles L.} and Denis Cournoyer and Carson, {Kenneth R.} and Jerome Rossert and Stefano Luminari and Evens, {Andrew M.} and Francesco Locatelli and Belknap, {Steven M.} and McKoy, {June M.} and Lyons, {E. Alison} and Benjamin Kim and Rishi Sharma and Stacey Costello and Toffelmire, {Edwin B.} and Wells, {George A.} and Messner, {Hans A.} and Yarnold, {Paul R.} and Trifilio, {Steven M.} and Raisch, {Dennis W.} and Kuzel, {Timothy M.} and Allen Nissenson and Lim, {Lay Cheng} and Tallman, {Martin S.} and Nicole Casadevall",
year = "2005",
month = "11",
day = "15",
doi = "10.1182/blood-2005-02-0508",
language = "English (US)",
volume = "106",
pages = "3343--3347",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

Bennett, CL, Cournoyer, D, Carson, KR, Rossert, J, Luminari, S, Evens, AM, Locatelli, F, Belknap, SM, McKoy, JM, Lyons, EA, Kim, B, Sharma, R, Costello, S, Toffelmire, EB, Wells, GA, Messner, HA, Yarnold, PR, Trifilio, SM, Raisch, DW, Kuzel, TM, Nissenson, A, Lim, LC, Tallman, MS & Casadevall, N 2005, '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', Blood, vol. 106, no. 10, pp. 3343-3347. https://doi.org/10.1182/blood-2005-02-0508

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. / Bennett, Charles L.; Cournoyer, Denis; Carson, Kenneth R.; Rossert, Jerome; Luminari, Stefano; Evens, Andrew M.; Locatelli, Francesco; Belknap, Steven M.; McKoy, June M.; Lyons, E. Alison; Kim, Benjamin; Sharma, Rishi; Costello, Stacey; Toffelmire, Edwin B.; Wells, George A.; Messner, Hans A.; Yarnold, Paul R.; Trifilio, Steven M.; Raisch, Dennis W.; Kuzel, Timothy M.; Nissenson, Allen; Lim, Lay Cheng; Tallman, Martin S.; Casadevall, Nicole.

In: Blood, Vol. 106, No. 10, 15.11.2005, p. 3343-3347.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Long-term outcome of individuals with pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant epoetin

T2 - A follow-up report from the Research on Adverse Drug Events and Reports (RADAR) Project

AU - Bennett, Charles L.

AU - Cournoyer, Denis

AU - Carson, Kenneth R.

AU - Rossert, Jerome

AU - Luminari, Stefano

AU - Evens, Andrew M.

AU - Locatelli, Francesco

AU - Belknap, Steven M.

AU - McKoy, June M.

AU - Lyons, E. Alison

AU - Kim, Benjamin

AU - Sharma, Rishi

AU - Costello, Stacey

AU - Toffelmire, Edwin B.

AU - Wells, George A.

AU - Messner, Hans A.

AU - Yarnold, Paul R.

AU - Trifilio, Steven M.

AU - Raisch, Dennis W.

AU - Kuzel, Timothy M.

AU - Nissenson, Allen

AU - Lim, Lay Cheng

AU - Tallman, Martin S.

AU - Casadevall, Nicole

PY - 2005/11/15

Y1 - 2005/11/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=27744500483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744500483&partnerID=8YFLogxK

U2 - 10.1182/blood-2005-02-0508

DO - 10.1182/blood-2005-02-0508

M3 - Review article

VL - 106

SP - 3343

EP - 3347

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -