Recombinant Factor VIII for the Treatment of Previously Untreated Patients with Hemophilia A -- Safety, Efficacy, and Development of Inhibitors

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Abstract
Although methods of viral attenuation in plasma-derived clotting-factor concentrates have improved, there is still a possibility that such concentrates may transmit certain blood-borne viruses. For this reason, the use of recombinant DNA-derived factor VIII (which is virus-free) to treat hemophilia A has generated considerable interest. We conducted a multicenter trial in previously untreated children with hemophilia A. They received recombinant factor VIII for all treatment or for prophylaxis and were evaluated at their respective clinics at intervals of no more than three months. Between January 1, 1989, and July 1, 1992, 95 patients who could be evaluated received recombinant factor VIII. By September 1, 1992, they had received the concentrate exclusively for 2.4 months to 3.5 years (median, 1.5 years). All responded well, with no treatment failures. A total of 3315 infusions were administered; there were three reports of minor adverse reactions. Inhibitor antibodies to factor VIII developed in 16 of 81 patients tested for them, after a median of nine days of exposure to factor VIII treatment. Inhibitor titers were or became low in 9 of the 16 patients despite continued episodic treatment with the concentrate. Inhibitors disappeared completely in 4 patients and remained at a low level (<10 Bethesda units) in 5 patients receiving episodic treatment. Transient or low levels of inhibitor, as observed in this study, may represent part of the natural history of hemophilia in infants. In view of the transient nature and lower concentration of the inhibitors detected and the generally satisfactory response to treatment, the benefits of recombinant factor VIII for the treatment of hemophilia seem to outweigh the risks.