Charles L. Bennett, M.D., Ph.D., M.P.P., Stefano Luminari, M.D., Allen R. Nissenson, M.D., Martin S. Tallman, M.D., Stephen A. Klinge, B.A., Norene McWilliams, J.D., M.P.H., June M. McKoy, M.D., J.D., M.P.H., Benjamin Kim, M.D., E. Allison Lyons, B.A., Steve M. Trifilio, R.P.H., Dennis W. Raisch, Ph.D., Andrew M. Evens, D.O., Timothy M. Kuzel, M.D., Glen T. Schumock, Pharm.D., M.B.A., Steven M. Belknap, M.D., Francesco Locatelli, M.D., Jerôme Rossert, M.D., Ph.D., and Nicole Casadevall, M.D.
Background Between 1988 and 1998, antibody-associated pure red-cellaplasia was reported in three patients who had undergone treatmentwith recombinant human erythropoietin (epoetin). Between 1998and 2000, 13 such cases were reported from France — 12in patients who had received the Eprex formulation of epoetinalfa and 1 in a patient who had received Neorecormon (a formulationof epoetin beta); both are products that are marketed outsidethe United States.
Methods We obtained reports of epoetin-associated pure red-cellaplasia from the Food and Drug Administration and from the manufacturersof Eprex, Epogen (another formulation of epoetin alfa), andNeorecormon. The numbers of case reports and estimates of exposure-adjustedincidence were analyzed according to the product, the causeof anemia, the route of administration, the country in whichpure red-cell aplasia was identified, and the date on whichpure red-cell aplasia was reported.
Results Between January 1998 and April 2004, 175 cases of epoetin-associatedpure red-cell aplasia were reported for Eprex, 11 cases forNeorecormon, and 5 cases for Epogen. Over half these cases hadoccurred in France, Canada, the United Kingdom, and Spain. Between2001 and 2003, the estimated exposure-adjusted incidence was18 cases per 100,000 patient-years for the Eprex formulationwithout human serum albumin, 6 per 100,000 patient-years forthe Eprex formulation with human serum albumin, 1 case per 100,000patient-years for Neorecormon, and 0.2 case per 100,000 patient-yearsfor Epogen. After procedures were adopted to ensure appropriatestorage, handling, and administration of Eprex to patients withchronic kidney disease, the exposure-adjusted incidence decreasedby 83 percent worldwide.
Conclusions After the peak incidence of Eprex-associated purered-cell aplasia was reached in 2001, interventions designedin response to drug-monitoring programs worldwide resulted ina reduction of more than 80 percent in the incidence of purered-cell aplasia due to Eprex.
Source Information
From the Midwest Center for Health Services Research and Policy Studies, Jesse Brown Veterans Affairs Medical Center (C.L.B.); Division of Hematology and Oncology (C.L.B., M.S.T., A.M.E., T.M.K.), Division of Geriatrics (J.M.M.), and Division of General Internal Medicine (S.M.B.), all in the Department of Medicine (B.K.); and Institute for Health Services Research and Policy Studies (C.L.B., S.A.K., N.M., E.A.L.), Northwestern University, Feinberg School of Medicine; Robert H. Lurie Comprehensive Cancer Center of Northwestern University (C.L.B., M.S.T., A.M.E., T.M.K.); Department of Pharmacy, Northwestern Memorial Hospital (S.T.); and Center for Pharmacoeconomic Research, College of Pharmacy, University of Illinois at Chicago (G.T.S.) — all in Chicago; Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia, Modena, Italy (S.L.); Division of Nephrology, David Geffen School of Medicine at the University of California, Los Angeles (A.R.N.); Veterans Affairs Cooperative Study Program Clinical Research Pharmaceutical Coordinating Center, University of New Mexico, Albuquerque (D.W.R.); Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy (F.L.); and Department of Nephrology, Tenon Hospital, Pierre and Marie Curie University (J.R.); and Department of Hematology, Hôtel-Dieu, and INSERM Unité 352 (N.C.) — all in Paris.
Address reprint requests to Dr. Bennett at the Midwest Center for Health Services and Policy Research, Jesse Brown Veterans Affairs Medical Center, 333 E. Huron St., Suite 277, Chicago, IL 60611, or at cbenne{at}northwestern.edu.
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