title: 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.
  
  
  CONCLUSIONS
  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(®).
authors.affiliation: Department of Renal Medicine, King's College Hospital, London, UK.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Macdougall
authors.affiliation: Service d'Immunologie et Hématologie Biologiques, Hôpital Saint Antoine, Paris, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Casadevall
authors.affiliation: Division of Nephrology and Dialysis, Alessandro Manzoni Hospital, Lecco, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Service de Néphrologie, Centre Hospitalier Universitaire de Bordeaux and Unité INSERM 1026, Université de Bordeaux, Bordeaux, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Combe
authors.affiliation: Centre de Recherche des Cordelliers, Ecole de Médecine, Paris, France.
authors.forename: Gerard M
authors.initials: GM
authors.lastname: London
authors.affiliation: Division of Nephrology and Dialysis, Hospital 'Dimiccoli', Barletta, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Paolo
authors.affiliation: Klinik für Nephrologie, Universitätsklinik Essen, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kribben
authors.affiliation: Department Internal Medicine IV, Universitätsklinik Homburg/Saar, Homburg/Saar, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Hans
authors.initials: H
authors.lastname: Messner
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University Melbourne, Melbourne, Australia.
authors.forename: John
authors.initials: J
authors.lastname: McNeil
authors.affiliation: Department of Renal Medicine, Kent and Canterbury Hospital, Canterbury, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Stevens
authors.affiliation: Dialysis and Hypertension Department, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S Orsola-Malpighi, Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Nephrology Department, Hospital Universitario Valdecilla, Santander, Spain.
authors.forename: Angel L M
authors.initials: AL
authors.lastname: De Francisco
authors.affiliation: Janssen, Pharmaceutical Companies of Johnson & Johnson, Titusville, NJ, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Percheson
authors.affiliation: Janssen, Pharmaceutical Companies of Johnson & Johnson, Titusville, NJ, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Potamianou
authors.affiliation: Janssen, Pharmaceutical Companies of Johnson & Johnson, Titusville, NJ, USA.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Foucher
authors.affiliation: Janssen, Pharmaceutical Companies of Johnson & Johnson, Titusville, NJ, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fife
authors.affiliation: Janssen, Pharmaceutical Companies of Johnson & Johnson, Titusville, NJ, USA.
authors.forename: Véronique
authors.initials: V
authors.lastname: Mérit
authors.affiliation: Janssen, Pharmaceutical Companies of Johnson & Johnson, Titusville, NJ, USA.
authors.forename: Els
authors.initials: E
authors.lastname: Vercammen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy; D001323:Autoantibodies / Q000097:blood*; D000068256:Darbepoetin alfa / Q000276:immunology; D000068817:Epoetin Alfa / Q000276:immunology; D004921:Erythropoietin / Q000276:immunology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000276:immunology; D012010:Red-Cell Aplasia, Pure / Q000453:epidemiology* / Q000276:immunology; D012042:Registries; D018570:Risk Assessment; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa
keywords: chronic kidney disease; darbepoetin alfa; epoetin alfa; epoetin beta; pure red cell aplasia