Baxter Healthcare Corporation reported findings from the "Analysis of Data from ADVATE® Prospective Trials" (ADAPT) study program database showing a statistically significant correlation between the amount of time that factor VIII (FVIII) blood levels are below one international unit per deciliter (1 IU/dL, 1% of normal factor VIII level) and an increase in the annual bleed rate in people with hemophilia A.
The ADAPT results were announced during the 21st Congress of the International Society on Thrombosis and Haemostasis, July 6-12, 2007, in Geneva, Switzerland. They appear to suggest that maintaining levels above 1 IU/dL with prophylactic therapy may decrease the number of bleeding episodes, especially in children. The findings were presented by Peter W. Collins, MD, FRCP, FRCPath, Department of Haematology, University Hospital of Wales, Cardiff, UK, one of the authors of the report.
"Until now there has been insufficient clinical evidence to demonstrate that factor VIII levels less than 1 IU/dL are associated with increased bleeding in patients receiving prophylaxis for the management of hemophilia A," said Collins.
Members of the ADAPT study group, all of whom had participated in Advate® clinical trials, included 48 children, ages one to six years old, and 100 adolescents and adults, ages 10 to 65 years old. All had severe hemophilia A, with factor VIII levels less than 1 IU/dL. The participants were initially evaluated in a 48-hour pharmacokinetic study to measure their rate of clearance of Advate® prior to beginning prophylactic therapy. The adolescent/adult group was on a fixed prophylaxis regimen, 3-4 times per week for 75 exposure days. The child group dosages were determined by the treating physician.
By examining each patient’s pharmacokinetic data and dosing, investigators estimated the median number of hours per week that the FVIII blood levels were below the 1 IU/dL trough level for each population—19.7 hours for the children and 16.5 hours for the adolescent/adult group. Subsequent comparison with bleed frequency for each group found that in the children’s group, the time that FVIII blood levels fell below 1 IU/dL while on prophylaxis was associated with increased incidence of traumatic and spontaneous bleeds. Similarly, in subjects who remained on a fixed prophylactic regimen in the adolescent/adult group, the duration of time below 1 IU/dL was associated with increased total joint bleeds.
"These results suggest that decreasing the amount of time a patient spends with a factor VIII less than 1 IU/dL will reduce the number of bleeds," said Collins. "This can be achieved in part by improving adherence to prescribed prophylaxis, while measurement of trough factor VIII levels in some patients may help individual tailoring of factor VIII dosing regimens."
Advate®, Baxter’s recombinant FVIII product, is indicated for the prevention and control of bleeding episodes and management of surgery-related bleeding in patients with hemophilia A.
Source: PRNewswire, July 10, 2007