Abstract
Eradication of factor VIII (FVIII) specific neutralizing antibodies (also known as
inhibitors) by the traditional method of immune tolerance induction (ITI) is costly
and unsuccessful in one out of three patients. Furthermore, effective inhibitor prevention
strategies are presently lacking. An overview is given in this narrative review of
antidrug antibody prevention or eradication strategies that have been used in disorders
beyond hemophilia A, with the aim of analyzing what we can learn from these strategies
for hemophilia A. Prevention of antidrug antibody formation using rituximab, methotrexate,
and intravenous immunoglobulins in patients with Pompe's disease seems effective but
carries a high risk of adverse events. Based on studies in patients with rheumatoid
arthritis and inflammatory bowel disease, it seems likely that treatment with methotrexate
alone would also be able to prevent inhibitor formation in hemophilia A patients.
Besides side effects, it is unclear whether immune tolerance to FVIII would persist
after cessation of immunomodulatory therapy with methotrexate. A combination of cyclophosphamide
and corticosteroids, used to treat antibody-mediated pure red cell aplasia, could
be further investigated to eradicate inhibitors in hemophilia A patients who are refractory
to ITI. In summary, insights gained from research on antidrug antibody formation in
other diseases could be helpful in devising alternative treatment strategies for inhibitor
development.
Keywords
inhibitor formation - immunomodulation - antidrug antibodies
