Hemophilia treatment. Immune tolerance induction: prospective clinical trials

Successful immune tolerance induction (ITI) relates significantly to the starting inhibitor titer but not the peak historical inhibitor titer. Below a starting titer of 10 BU/mL success appears to be unrelated to the dose of factor VIII (FVIII) used for ITI. Above this starting titer, larger doses of FVIII may be associated with a better outcome from ITI. Opinion on the importance of the dose of FVIII used for ITI is polarized and there is no agreement on the optimal regimen for ITI. A prospective randomized clinical trial is proposed in which patients will initially be treated on demand with bypass therapy until the inhibitor titer has fallen below 10 BU/mL. Patients will then be randomized to receive a high or low-dose regime. Efficacy, cost-effectiveness and morbidity will be compared.