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

Subcutaneous administration of Eprex(A (R)) (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(A (R)) and to compare this with the PRCA incidence with subcutaneous NeoRecormon(A (R)) (epoetin beta) and Aranesp(A (R)) (darbepoetin alfa). PRIMS was a multicentre, multinational, non-interventional, parallel-group, immunogenicity surveillance registry. Adults with CKD receiving or about to initiate subcutaneous Eprex(A (R)), NeoRecormon(A (R)) or Aranesp(A (R)) 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. Of the 15 333 patients enrolled, 5948 received Eprex(A (R)) (8377 patient-years) and 9356 received NeoRecormon(A (R))/Aranesp(A (R)) (14 286 patient-years). No treatment data were available for 29 patients. Among 23 patients with LOE, five cases of PRCA were confirmed (Eprex(A (R)), n = 3; NeoRecormon(A (R)), n = 1; Aranesp(A (R)), n = 1). Based on exposed time, PRCA incidence was 35.8/100 000 patient-years (95% CI 7.4-104.7) for Eprex(A (R)) versus 14.0/100 000 patient-years (95% CI 1.7-50.6) for NeoRecormon(A (R))/Aranesp(A (R)). The incidence of PRCA with Eprex(A)(R) 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. This large, prospective registry demonstrates that PRCA is rare with subcutaneous administration of either the new coated-stopper syringe presentation of Eprex(A (R)), or NeoRecormon(A (R)) or Aranesp(A (R)).