title: Clinical safety of biosimilar recombinant human erythropoietins.
abstract: BACKGROUND
  A "biosimilar" or "similar biological medicinal product" is a biological agent that is similar in terms of quality, safety, and efficacy to an authorized reference biological medicine. Since the expiration of the epoetin alfa patent in Europe, three agents have received marketing authorization from the European Medicines Agency: Binocrit (epoetin alfa; aka Abseamed and Epoetin Alfa Hexal), Retacrit (epoetin zeta; aka Silapo), and Eporatio (epoetin theta; aka Biopoin and Ratioepo).
  
  
  METHODS
  Using the EMA dossiers and journal publications, this article reviews clinical safety data for these products, with emphasis on serious/severe adverse events and a special consideration of immunogenicity, venous thromboembolism, and mortality.
  
  
  CONCLUSIONS
  A review of the available safety evidence shows that all three agents discussed have similar safety profiles. None were statistically higher on safety parameters to what is known about ESA as a class, when stratified by population. As with ESAs in general, immunogenicity, venous thromboembolism, and mortality are all concerns. What is known about ESAs regarding safety can be extended to biosimilar erythropoietins. Since biosimilars are unique, complex biological molecules, safety profiles may evolve from common to differentiated, once long-term product-specific safety data are available. Large-sample, long-term, observational studies of real-world practice will provide the heterogeneity and statistical power to demonstrate product-specific effectiveness and safety profiles. Statistically, out of the commercially available formulations of the three products reviewed, no single product is less or more safe.
authors.affiliation: Center for Health Outcomes and Pharmaco-Economic Research, College of Pharmacy, University of Arizona, 1295 N. Martin Ave., Matrix 45, Tucson, AZ 85721, USA. abraham@pharmacy.arizona.edu
authors.forename: Ivo
authors.initials: I
authors.lastname: Abraham
authors.forename: Karen
authors.initials: K
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects* / Q000737:chemistry; D004342:Drug Hypersensitivity / Q000453:epidemiology; D016903:Drug Monitoring; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects* / Q000737:chemistry; D006397:Hematinics / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D015994:Incidence; D060735:Pharmacovigilance; D011994:Recombinant Proteins / Q000009:adverse effects / Q000737:chemistry; D054556:Venous Thromboembolism / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality
chemical_list: D059451:Biosimilar Pharmaceuticals; C554270:EPO protein, human; D006397:Hematinics; D011994:Recombinant Proteins; C555712:epoetin theta; C530192:epoetin zeta; D004921:Erythropoietin; D000068817:Epoetin Alfa