Immune tolerance therapy dose as an outcome predictor

The question of dose as a successful ITT outcome predictor in haemophilia A and B is an important one on many levels. Increased morbidity associated with inhibitor development has been documented. Currently, immune tolerance is the only proven method for inhibitor eradication. Furthermore, given the morbidity and the high cost of less effective bypass therapy, a study by Harvard health economists using Markov decision analysis predicted an increased life expectancy of 4.5 years at a lifetime cost savings of $1.6 million with the use of ITT rather than lifelong APCC therapy. However, the immediate short-term cost of this expensive therapeutic intervention has the capacity to strain the financial resources of many countries in the developed world, regardless of the system of medical reimbursement. It also assures the inaccessibility of this treatment modality to most of the world's inhibitor patients living in the developing world. Cost aside, recent experience has taught us that clotting factor supply is precarious, not inexhaustible as previously assumed. Finally, in the paediatric patient who is most likely to require and undergo ITT, venous access for daily infusions is problematic with or without a central venous access device. Indeed, for these reasons alone, finding the answer to the question of optimal cost-effective dosing immune tolerance is a matter of medical urgency and moral obligation to the global haemophilia community.