Published: 10 June 2015

Risk of Inhibitor Development with Factor VIII Replacement Products

Prescriber Update 36(2): 21
June 2015

Key Messages

  • The risk of inhibitor (autoantibody) development is comparable for plasma-derived and recombinant factor VIII products.
  • The current data is insufficient to determine if the risk of inhibitor development varies between different recombinant products.


Recently published clinical studies have raised the possibility that different factor VIII replacement products are associated with different risks of inhibitor development.

Factor VIII replacement products are used to prevent and treat bleeding in patients with haemophilia. Factor VIII concentrates are either plasma-derived or recombinant products.

The major adverse reaction of concern is the development of autoantibodies known as inhibitors. Inhibitors prevent the clotting action of factor VIII risking fatal and disabling bleeds in the patient.

The risk factors for development of factor VIII inhibitors are numerous and not yet fully understood, they include patient related factors as well as therapy related factors.

In 2013, the results of the RODIN study were published1. In this study, there was no difference in terms of inhibitor development between plasma-derived and recombinant products1. However, comparison of different recombinant products found a higher incidence of inhibitor development in patients treated with Kogenate FS compared to Advate1.

The Medicines Adverse Reactions Committee (MARC) has reviewed data from the RODIN study. In addition, information from cohorts and registries of haemophilia patients in France, Canada, the UK and Europe were considered2-5.

The MARC concluded these data were inconclusive and no definite difference between products was demonstrated. The MARC considered that prescribers and patients should continue to use the product that best suits the needs of the patient. The minutes from the meeting are published on the Medsafe website (

  1. Gouw SC, van der Bom JG, Ljung R, et al. 2013. Factor VIII products and inhibitor development in severe hemophilia A. The New England Journal of Medicine 368: 231–239.
  2. Calvez T, Chambost H, Claeyssens-Donadel S, et al. 2014. Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A. Blood 124: 3398–3408.
  3. Collins PW, Palmer BP, Chalmers EA, et al. 2014. Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A, 2000-2011. Blood 124: 3389–3397.
  4. Vezina C, Carcao M, Infante-Rivard C, et al. 2014. Incidence and risk factors for inhibitor development in previously untreated severe haemophilia A patients born between 2005 and 2010. Haemophilia 20: 771–776.
  5. Fischer K, Lassila R, Peyvandi F, et al. 2015. Inhibitor development in haemophilia according to concentrate. Four-year results from the European Haemophilia Safety Surveillance (EUHASS) project. Thrombosis and Haemostasis 113: 968–975.