title: Results from a safety cohort of patients with renal anemia receiving the biosimilar epoetinzeta: The PASCO I study.
abstract: BACKGROUND
  Epoetin-zeta (epoetin-ζ) (sold as Retacrit™/Silapo™) is a biologic product that was approved by the European Medicines Agency in 2007 after demonstrating biosimilarity to its reference product epoetin-α (Eprex™), based on a comprehensive comparability exercise including extensive biophysical characterization and three double-blind randomized controlled trials. Since 2008, epoetin-ζ has been prescribed by physicians across Europe to treat anemia of renal disease in many thousands of patients.
  
  
  METHODS
  Provided here are results of the PASCO I study (post-authorization safety cohort observation of silapo/retacrit (epoetin-ζ) administered intravenously for the treatment of renal anemia). The primary study endpoint was the frequency of adverse events of special interest (AESI) occurring in patients receiving epoetin-ζ over a 1-year study observation period.
  
  
  RESULTS
  The safety set included 1,634 patients who received at least 1 dose of epoetin-ζ during the study period. These patients experienced AESI at these frequencies: clotting of artificial kidney 9.8%, lack of efficacy 2.3%, cerebrovascular events (including cerebrovascular accident, cerebral infarction, cerebral hemorrhage, and transient ischemic attack) 1.8%, myocardial infarction 1.7%, acute myocardial infarction 1.2%, clinically relevant hyperkalemia 0.4%, deep vein thrombosis 0.2%, convulsion 0.2%, hypertensive encephalopathy 0.1%, and pulmonary embolism 0.1%. No patients were reported as having anaphylactoid reactions, angioedema, erythropoietinneutralizing antibodies, or pure red cell aplasia. The median weekly follow-up dose of epoetin-ζ was 158.6 IU/kg. Mean hemoglobin concentration ranged between 11.3 and 11.7 g/dL. From the safety set, 228 patients died (14.0%), while 1,135 patients (74.9%; excluding 119 with data missing) continued treatment with epoetin-ζ following the 12-month observation.
  
  
  CONCLUSIONS
  The PASCO I study contributes significantly to current knowledge about the frequency of adverse events associated with the use of epoetin-ζ for the treatment of renal anemia and demonstrates a pattern of adverse events comparable with data for other existing epoetin products in Europe.
authors.forename: Frank
authors.initials: F
authors.lastname: Dellanna
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Fluck
authors.forename: Gerhard
authors.initials: G
authors.lastname: Lonnemann
authors.forename: Clarissa A
authors.initials: CA
authors.lastname: Wild
authors.forename: Andreas
authors.initials: A
authors.lastname: Iwanowitsch
authors.forename: Rene
authors.initials: R
authors.lastname: Meissner
authors.forename: Paul
authors.initials: P
authors.lastname: Audhya
mesh_terms: D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects*; D004921:Erythropoietin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D006435:Renal Dialysis / Q000009:adverse effects
chemical_list: D059451:Biosimilar Pharmaceuticals; D006454:Hemoglobins; D011994:Recombinant Proteins; C530192:epoetin zeta; D004921:Erythropoietin