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Semin Thromb Hemost 2018; 44(06): 531-543
DOI: 10.1055/s-0038-1666823
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Preventing or Eradicating Factor VIII Antibody Formation in Patients with Hemophilia A: What Can We Learn from Other Disorders?

Shermarke Hassan
1   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
,
Karin Fijnvandraat
2   Department of Pediatric Hematology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
3   Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands
,
Johanna G. van der Bom
1   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
4   Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands
,
Samantha C. Gouw
1   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
2   Department of Pediatric Hematology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
› Author Affiliations
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Publication History

Publication Date:
25 July 2018 (online)

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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
 

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