Inhibitors: A Need for Eradication?

Acta Haematol. 2019;141(3):151-155. doi: 10.1159/000495454. Epub 2019 Feb 15.

Abstract

The development of inhibitors against factor VIII (FVIII) concentrates represents a significant treatment complication for hemophilia. Immune tolerance induction (ITI) therapy eradicates inhibitors in 60-80% of patients, resulting in a normal FVIII response. This article, based on presentations at the 6th International Coagulation Meeting, held in Barcelona, Spain, in September 2017, provides an overview of management approaches for patients with inhibitors and briefly tabulates four cases of ITI therapy (first-line or rescue ITI therapy in pediatric and adult patients) with successful outcomes. Switching FVIII product from recombinant FVIII to plasma-derived FVIII/VWF concentrate may be helpful in eradicating inhibitors. The rate of decline of inhibitor titer in the initial stages of ITI therapy is a good indicator of the success or failure of therapy, although prognostic biomarkers are needed. The development of the bispecific monoclonal antibody emicizumab, which was recently shown to reduce bleeding in inhibitor patients, offers a potential alternative therapeutic option. However, the benefits of inhibitor eradication, including a wider choice of cheaper therapeutic products for preventing and treating bleeds, suggest that at least one attempt of ITI therapy should be offered to patients who develop inhibitors.

Keywords: Factor VIII concentrate; Hemophilia; Immune tolerance induction; Inhibitors; Von Willebrand factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Bispecific / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Blood Coagulation Factor Inhibitors* / antagonists & inhibitors
  • Blood Coagulation Factor Inhibitors* / blood
  • Blood Coagulation Factor Inhibitors* / immunology
  • Congresses as Topic
  • Factor VIII* / antagonists & inhibitors
  • Factor VIII* / therapeutic use
  • Hemophilia A* / blood
  • Hemophilia A* / drug therapy
  • Hemophilia A* / immunology
  • Humans
  • Immune Tolerance / drug effects*

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Humanized
  • Blood Coagulation Factor Inhibitors
  • emicizumab
  • F8 protein, human
  • Factor VIII