Incidence of erythropoietin antibody-mediated pure red cell aplasia: The Prospective Immunogenicity Surveillance Registry (PRIMS)

Abstract

Background Subcutaneous administration of Eprex ® (epoetin alfa) in patients with chronic kidney disease (CKD) was contraindicated in the European Union between 2002 and 2006 after increased reports of anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA). The Prospective Immunogenicity Surveillance Registry (PRIMS) was conducted to estimate the incidence of antibody-mediated PRCA with subcutaneous administration of a new coated-stopper syringe presentation of Eprex ® and to compare this with the PRCA incidence with subcutaneous NeoRecormon ® (epoetin beta) and Aranesp ® (darbepoetin alfa). Methods PRIMS was a multicentre, multinational, non-interventional, parallel-group, immunogenicity surveillance registry. Adults with CKD receiving or about to initiate subcutaneous Eprex ®, NeoRecormon ® or Aranesp ® for anaemia were enrolled and followed for up to 3 years. Unexplained loss or lack of effect (LOE), including suspected PRCA, was reported, with antibody testing for confirmation of PRCA. Results Of the 15 333 patients enrolled, 5948 received Eprex ® (8377 patient-years) and 9356 received NeoRecormon ® /Aranesp ® (14 286 patient-years). No treatment data were available for 29 patients. Among 23 patients with LOE, five cases of PRCA were confirmed (Eprex ®, n = 3; NeoRecormon ®, n = 1; Aranesp ®, n = 1). Based on exposed time, PRCA incidence was 35.8/100 000 patient-years (95% CI 7.4-104.7) for Eprex ® versus 14.0/100 000 patient-years (95% CI 1.7-50.6) for NeoRecormon ® /Aranesp ®. The incidence of PRCA with Eprex ® was not significantly different versus comparator ESAs (rate ratio: 2.56; 95% CI 0.43-15.31). An analysis based on observed time produced similar findings. Conclusion This large, prospective registry demonstrates that PRCA is rare with subcutaneous administration of either the new coated-stopper syringe presentation of Eprex ®, or NeoRecormon ® or Aranesp ®.