Use of the UKHCDO Database for a postmarketing surveillance study of different doses of recombinant factor VIIa in haemophilia

Introduction: Recombinant factor VIIa (rFVIIa) is recommended in Europe at standard (3 x 90 mu g kg(-1)) or high (1 x 270 mu g 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. Aim: 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 mu g kg(-1)), intermediate (>= 90-<180 mu g kg(-1)) or high (>= 180-<270 or >= 270 mu g 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 mu g kg(-1)) than acquired haemophilia (90.5 mu g 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. Conclusion: The novel use of a national database for postmarketing surveillance has demonstrated acceptable safety for all recommended doses of rFVIIa.