Strategies for reducing inhibitor formation in severe haemophilia.

Abstract

The greatest barrier to successful haemophilia A care in resource-rich countries is the development of inhibitors to therapeutic factor VIII. Children with inhibitors suffer through increased bleeding and joint damage as well as frequent venepuncture. Costs associated with inhibitors are beyond many healthcare systems. Over the last two decades, there has been no improvement in our ability to reduce inhibitor development. Current strategies based on early prophylaxis and avoidance of immunological danger signals have given rise to conflicting results. Registry data suggest an increasing problem. Our understanding of the immunological systems involved in inhibitor formation should inform efforts to prevent inhibitors. Great efforts with mouse models are being undertaken in this field. However, there is no guarantee of the availability of any new agents arising from experimental work in the near future. Global immunomodulatory agents may be one solution. Compounds with a long history of use in inflammatory conditions have demonstrated efficacy in preventing antibodies to protein therapeutics both in animal models and in humans. As these compounds have a long history of use in humans, including babies, it may be that these agents offer an option for reducing inhibitor formation in previously untreated patients.