title: Use of the UKHCDO Database for a postmarketing surveillance study of different doses of recombinant factor VIIa in haemophilia.
abstract: BACKGROUND
  Recombinant factor VIIa (rFVIIa) is recommended in Europe at standard (3 × 90 μg kg-1) or high (1 × 270 μg kg-1) doses. When granting the license for the high dose, the European Medicines Agency (EMA) requested postmarketing surveillance for thrombosis. This was conducted by the United Kingdom National Haemophilia Database (NHD) on behalf of Novo Nordisk and the EMA.
  
  
  OBJECTIVE
  To assess the use and safety of rFVIIa utilizing prospective data collected by the NHD (1 January 2008 to 30 June 2011).
  
  
  RESULTS
  Data were obtained from 67 haemophilia A/B patients with inhibitors treated for 1057 bleeds and 31 acquired haemophilia patients treated for 70 bleeds. Initial rFVIIa dose was categorized post hoc as low (<90 μg kg-1), intermediate (≥90-<180 μg kg-1) or high (≥180-<270 or ≥270 μg kg-1). For haemophilia A/B, high and lower initial rFVIIa dose was used for 38.4% and 51.4% of episodes, respectively, while for acquired haemophilia, the values were 11.4% and 77.1% respectively. Median initial doses were higher for haemophilia A/B (146.3 μg kg-1) than acquired haemophilia (90.5 μg kg-1). A single administration of rFVIIa was the most frequently used regimen for haemophilia A/B, in contrast with standard recommendations and previous reports. For acquired haemophilia, most episodes were treated with multiple doses. No adverse drug reactions or thromboembolic events were reported for any rFVIIa dose.
  
  
  CONCLUSIONS
  The novel use of a national database for postmarketing surveillance has demonstrated acceptable safety for all recommended doses of rFVIIa.
authors.affiliation: University Department of Haematology, Manchester Royal Infirmary, Manchester, UK.|UK National Haemophilia Database, Manchester, UK.
authors.forename: C R M
authors.initials: CRM
authors.lastname: Hay
authors.affiliation: UK National Haemophilia Database, Manchester, UK.
authors.forename: T
authors.initials: T
authors.lastname: Sharpe
authors.affiliation: Department of Haematology, Guys and St Thomas' Hospital, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Dolan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D015942:Factor VIIa / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing / Q000706:statistics & numerical data*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D006113:United Kingdom; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: National Haemophilia Database; rFVIIa; real-world use