Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study

Summary. Background: Prophylactic treatment for severe hemophilia A is likely to be more effective than treatment when bleeding occurs, however, prophylaxis is costly. We studied an inception cohort of 25 boys using a tailored prophylaxis approach to see if clotting factor use could be reduced with acceptable outcomes. Methods: Ten Canadian centers enrolled subjects in this 5-year study. Children were followed every 3 months at a comprehensive care hemophilia clinic. They were initially treated with once-weekly clotting factor; the frequency was escalated in a stepwise fashion if unacceptable bleeding occurred. Bleeding frequency, target joint development, physiotherapy and radiographic outcomes, as well as resource utilization, were determined prospectively. Results: The median follow-up time was 4.1 years (total 96.9 person-years). The median time to escalate to twice-weekly therapy was 3.42 years (lower 95% confidence limit 2.05 years). Nine subjects developed target joints at a rate of 0.09 per person-year. There was an average of 1.2 joint bleeds per person-year. The cohort consumed on average 3656 IU kg−1year−1 of factor (F) VIII. Ten subjects required central venous catheters (three while on study); no complications of these devices were seen. One subject developed a transient FVIII inhibitor. End-of-study joint examination scores – both clinically and radiographically – were normal or near-normal. Conclusions: Most boys with severe hemophilia A will probably have little bleeding and good joint function with tailored prophylaxis, while infusing less FVIII than usually required for traditional prophylaxis.