Epoetin-associated pure red cell aplasia

Past, present, and future considerations

June M McKoy, Robin E. Stonecash, Denis Cournoyer, Jerome Rossert, Allen R. Nissenson, Dennis W. Raisch, Nicole Casadevall, Charles L. Bennett

Research output: Contribution to journalReview article

124 Citations (Scopus)

Abstract

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. STUDY DESIGN AND 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)1754-1762
Number of pages9
JournalTransfusion
Volume48
Issue number8
DOIs
StatePublished - Aug 1 2008

Fingerprint

Pure Red-Cell Aplasia
Epoetin Alfa
Erythropoietin
Renal Dialysis
United States Food and Drug Administration
Serum Albumin
Canada
Antibodies
Singapore
Rubber
Syringes
Polytetrafluoroethylene
Paris
Causality
Anemia
Research Personnel
Databases

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

Cite this

McKoy, J. M., Stonecash, R. E., Cournoyer, D., Rossert, J., Nissenson, A. R., Raisch, D. W., ... Bennett, C. L. (2008). Epoetin-associated pure red cell aplasia: Past, present, and future considerations. Transfusion, 48(8), 1754-1762. https://doi.org/10.1111/j.1537-2995.2008.01749.x
McKoy, June M ; Stonecash, Robin E. ; Cournoyer, Denis ; Rossert, Jerome ; Nissenson, Allen R. ; Raisch, Dennis W. ; Casadevall, Nicole ; Bennett, Charles L. / Epoetin-associated pure red cell aplasia : Past, present, and future considerations. In: Transfusion. 2008 ; Vol. 48, No. 8. pp. 1754-1762.
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abstract = "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. STUDY DESIGN AND 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. CONCLUSION: 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.",
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McKoy, JM, Stonecash, RE, Cournoyer, D, Rossert, J, Nissenson, AR, Raisch, DW, Casadevall, N & Bennett, CL 2008, 'Epoetin-associated pure red cell aplasia: Past, present, and future considerations', Transfusion, vol. 48, no. 8, pp. 1754-1762. https://doi.org/10.1111/j.1537-2995.2008.01749.x

Epoetin-associated pure red cell aplasia : Past, present, and future considerations. / McKoy, June M; Stonecash, Robin E.; Cournoyer, Denis; Rossert, Jerome; Nissenson, Allen R.; Raisch, Dennis W.; Casadevall, Nicole; Bennett, Charles L.

In: Transfusion, Vol. 48, No. 8, 01.08.2008, p. 1754-1762.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Epoetin-associated pure red cell aplasia

T2 - Past, present, and future considerations

AU - McKoy, June M

AU - Stonecash, Robin E.

AU - Cournoyer, Denis

AU - Rossert, Jerome

AU - Nissenson, Allen R.

AU - Raisch, Dennis W.

AU - Casadevall, Nicole

AU - Bennett, Charles L.

PY - 2008/8/1

Y1 - 2008/8/1

N2 - 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. STUDY DESIGN AND 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. CONCLUSION: 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.

AB - 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. STUDY DESIGN AND 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. CONCLUSION: 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.

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McKoy JM, Stonecash RE, Cournoyer D, Rossert J, Nissenson AR, Raisch DW et al. Epoetin-associated pure red cell aplasia: Past, present, and future considerations. Transfusion. 2008 Aug 1;48(8):1754-1762. https://doi.org/10.1111/j.1537-2995.2008.01749.x