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A multicenter study of recombinant factor VIII (recombinate): safety,
efficacy, and inhibitor risk in previously untreated patients with
hemophilia A. The Recombinate Study Group
GL Bray, ED Gomperts, S Courter, R Gruppo, EM Gordon, M Manco-Johnson, A Shapiro, E Scheibel, G White and M Lee
Department of Hematology/Oncology, Children's National Medical Center,
Washington, DC.
In July 1990, the Recombinate Study Group initiated a prospective, open-
labeled investigation of recombinant factor VIII (r-FVIII) to assess its
safety and efficacy and to characterize the natural history of inhibitor
development in previously untreated patients (PUPs) with hemophilia A. All
study subjects have severe FVIII deficiency (baseline FVIII level < or =
2% of normal) and no history of blood product exposure before study entry.
Following the first r-FVIII infusion, plasma was screened for inhibitors
once every 3 months, and plasma recovery of r-FVIII at 30 minutes and 24
hours postinfusion was assayed at least once every 6 months. As of May
1993, 73 of 79 patients originally enrolled in the trial continue to
participate. The median number of r-FVIII exposure-days for the 71 subjects
who have received at least one r-FVIII infusion is 11. A total of 1,785
infusions have been administered to treat 810 bleeding events. Ninety-two
percent of bleeding events responded as anticipated to one or two
infusions. Two, nonrecurring, acute adverse reactions occurred coincident
with r-FVIII infusion, one of which was unrelated and the other, possibly
related to the infusion. Seventeen (23.9%) subjects have developed
inhibitors: five with peak titers more than 10 Bethesda units (BU) and 12
with peak titers < or = 10 BU (range, 0.5 to 10). Survival analysis
showed that the probability of remaining inhibitor-free in this group of
patients with severe hemophilia A is 88.4% after 8, 73.6% after 10, and
61.6% after 25 r-FVIII exposure-days. Inhibitors disappeared in five
(29.4%) subjects on retesting 2 to 16 months after the last positive
inhibitor assay. r-FVIII is safe and effective in the treatment of
hemophilia A- related bleeding. To date, the inhibitor risk associated with
its use is comparable to that in patients treated with plasma-derived
concentrates. The majority of inhibitors identified are low in titer and do
not preclude continued on-demand therapy with r-FVIII.
Volume 83,
Issue 9,
pp. 2428-2435,
05/01/1994
Copyright © 1994 by The American Society of Hematology
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