Frequency-Escalated Prophylaxis for Severe Hemophilia A Reduces Clotting Factor Usage with Minimal Long-Term Arthropathy

Tailored frequency-escalated prophylaxis results in minimal long-term arthropathy and very good health outcomes, while reducing the quantity of costly clotting factor as compared with standard prophylaxis protocols, according to a 16-year longitudinal study of Canadian boys with severe hemophilia A.

Between June 1997 and January 2007, 12 centers participating in the Canadian Hemophilia Prophylaxis Study enrolled 56 boys ages 1.0 years to 2.5 years, and followed them for a median of 10.2 years. Study participants were treated with standard half-life recombinant factor VIII, beginning as once-weekly prophylaxis at 50 IU/kg and escalating in frequency (with accompanying dose adjustments) in response to breakthrough bleeding as determined by the protocol. The primary endpoint was joint health, as measured at study end by the modified Colorado Child Physical Examination Scores (CCPES).

The median end-of-study CCPES physical examination score was 1 (IQR 1-3; range 0-12) for the left ankle and 1 (IQR 1-2; 0- 12) for the right ankle, with all other joints having a median score of 0. No treatment-related safety events occurred over the course of the study. The median annualized index joint bleeding rate was 0.95 per year (IQR 0.44-1.35; range 0.00-13.43), but 17 (30%) patients had protocol-defined unacceptable breakthrough bleeding at some point during the study.

While concluding that tailored frequency-escalated prophylaxis leads to very little arthropathy and a reduced quantity of clotting factor as compared to standard prophylaxis, the investigators called for future studies employing a more stringent protocol to address some bleeding sequelae still observed in this study.