The use of recombinant factor VIII products in previously treated patients with hemophilia A: Pharmacokinetics, efficacy, safety, and inhibitor development

Studies in previously treated patients (PTPs) have been conducted for the three recombinant factor VIII (rFVIII) concentrates currently licensed. Kogenate(R) has shown a recovery of 2.7% per IU/kg and a half-life of 15.8 hours. A prospective 5-year study in 58 patients showed that 82% of bleeds resolved with one treatment; the average dose was 25 IU/kg. For Recombinate(R), the recovery was 2.4% per IU/kg and the half-life was 14.7 hours. In 69 patients, the average dose used to treat a bleed was 27.5 IU/kg, and 91% of responses were categorized as good or excellent. B-domain depleted rFVIII, Refacto(R), has shown a recovery of 2.7% per IU/kg and a half-life of 14 hours. In 113 PTPs, the average dose used was 29.5 IU/kg, and 71% of bleeds responded to one treatment. All three recombinant products have been shown to be safe and effective in very similar dosing regimens. In view of the good recoveries, it is probable that smaller doses, such as 20 IU/kg, could be recommended to treat a bleed effectively with one dose, given that dosing regimens were previously established using intermediate products. Clearly, this would have considerable financial advantages.