Background:
Bleeding risk during physical activities for persons with hemophilia has been shown to be reduced with adequate factor levels (Broderick 2012). With extended half-life Factor VIII and IX products offering opportunities for longer intervals between infusions, it is important to understand the bleeding risk for patients who have an active lifestyle.
Objective:
To evaluate the relative risk of bleeding between prophylaxis schedules using recombinant Factor VIII (rFVIII) vs. rFVIII-Fc among different patient physical activity profiles
Methods:
A mathematical model based on the literature was developed. Factor levels were estimated using a one-compartment pharmacokinetic model (Collins 2010). Half-life and incremental recovery values were taken from a crossover study of rFVIII and rFVIII-Fc (Mahlangu 2014). Five prophylaxis regimens were evaluated: two common to rFVIII (30IU/kg every other day (EOD); 35IU/kg 3x/week) and three studied in the rFVIII-Fc pivotal trial (2x/ week: 25IU/kg covering 3 days and 50IU/kg covering 4 days per week; 50IU/kg every 5 days; 65IU/kg 1x/week). Activities such as swimming, running and wrestling were classified as Type 1, Type 2, and Type 3 in Broderick 2012, derived from the NHF “Playing It Safe Brochure” (Anderson 2005). Risk of bleeding by activity category and factor level at time of activity was calculated using the odds ratio values from Broderick 2012. Three hypothetical patient activity profiles were evaluated: Consistently Active (M-Sun: Type 2 activities), Regular Exerciser (M-F: Type 2 activities, Sat-Sun: Type 1 activities), and Weekend Warrior (TThSun: Type 1 activities, MWF: Type 2 activities, Sat: Type 3 activities). For each regimen, the infusion schedule with the lowest bleeding risk for each patient activity profile was selected. The relative bleeding risk vs. the best prophylaxis regimen was estimated and compared for the activity profiles.
Results:
rFVIII 30IU/kg EOD and 35IU/kg 3x/week achieved the two lowest bleeding risk for all three patient activity profiles. Compared to rFVIII every other day, bleeding risk was increased by 20%, 25% and 46% for the Consistently Active patient prescribed rFVIII-Fc twice per week, every 5 days, and 1x/week, respectively. Compared to rFVIII 3x/week, bleeding risk was increased by 20%, 30% and 44% for the Regular Exerciser and by 21%, 32% and 45% for the Weekend Warrior prescribed rFVIII-Fc 2x/week, every 5 days, and 1x/ week, respectively.
Conclusion:
This model suggests that active patients characterized with the above profiles may have reduced bleeding risk with rFVIII compared to extended half-life FVIII dosing regimens evaluated in this analysis.