Long-Term Follow-Up of 98 Cases of Recombinant Human Erythropoietin (epoetin) Induced Pure Red Cell Aplasia (PRCA): Outcomes and Treatment Data from the Research on Adverse Drug Reactions and Reports (RADAR) Program

Background: With the recent reporting of 191 cases of epoetin induced PRCA (Bennett CL, NEJM 2004), information is needed about the long-term follow-up of individuals with this diagnosis. While 47 cases from France, Germany, and England have been reported recently (Verhelst D, Lancet 2004), these data are limited by short follow-up and absence of information from other regions. Methods: RADAR investigators identified cases of epoetin-associated PRCA from the Food and Drug Administration MEDWatch database and proprietary reports from both the manufacturers epoetin alpha (Epogen from AMGEN, and Eprex from Johnson and Johnson) and epoetin beta (Neorecormon from Roche). Patients exposed to more than one epoetin form were excluded. PRCA recovery was operationally defined as transfusion independence, clearance of anti-erythropoietin antibody, and/or normalization of reticulocyte count. Results: See table. Conclusions: The overall recovery rate of 82% following transplantation versus 40% following immunosuppression suggests that transplantation might be the optimal therapy for epoetin-associated PRCA. Almost half of the patients rechallenged with epoetin developed recurrent PRCA, raising concern over the benefits of rechallenge. Eprex (N=82) Neorecormon (N=11) Epogen (N=5) Origin: US 60% 64% 100% Europe 60% 64% – Pacific Rim/Asia 21% 36% – Canada 19% – – Subcutaneous delivery 99% 100% 60% Recovery with Immunosuppression 37% 73% 0% Recovery with renal Transplant 11% – – No recovery with renal transplant 1% – 20% No Recovery 41% 18% 40% Unknown Recovery 10% 9% 40% Male gender 68% 73% 40% Rechallenged with epoetin N=12 – – Response rate 50% Median age 68 years 47 years 51 years