Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates

Human plasma-derived factor IX (pdFIX) concentrates are routinely used to t reat patients with hemophilia B, an X-linked bleeding disorder that affects 1 in 30 000 males, but concerns remain regarding transmission of blood-bor ne pathogens. Therefore, the safety and efficacy of recombinant human facto r IX (rFIX) were evaluated, A 20-center international trial was conducted i n previously treated patients with severe or moderate (< 5 IU/dL factor IX activity) hemophilia B. Participants received rFIX for pharmacokinetic stud ies, treatment of or prophylaxis against hemorrhage, or surgical hemostasis , and were assessed at 3-month intervals for 2 years. Fifty-six subjects we re treated. Mean incremental rFIX recovery was 0.75 IU/dL per IU/kg, 30% lo wer than expected for pdFIX, although the mean half-life was similar. Pharm acokinetic parameters were stable over time. Somewhat lower recoveries were seen in subjects younger than 15 years of age and in those with no detecta ble factor IX antigen. A total of 7362 infusions of rFIX were administered. All 1796 hemorrhages were controlled, 80.9% of which required only one rFI X infusion. Effective hemostasis was also achieved in prophylactic and surg ical settings. One individual developed a low titer (1.2 Bethesda unit) tra nsient inhibitor that spontaneously resolved. rFIX was not associated with serious adverse events, thrombogenicity, or virus transmission. rFIX Is saf e and effective for the treatment of hemophilia B. Despite a lower recovery compared with pdFIX, rFIX controlled hemorrhage in a wide variety of setti ngs and may provide a safety advantage In terms of risk from blood-borne pa thogens. (C) 2001 by The American Society of Hematology.