Epidemiological aspects of inhibitor development in hemophilia and strategies of management

ABSTRACT

Introduction: The most severe complication associated with FVIII and FIX replacement therapy is the development of inhibitory antibodies against FVIII or FIX (inhibitors), affecting approximately 20–35% of patients with severe hemophilia A.

Areas covered: The aim of this review is to provide, through a systematic database search, an update on the epidemiological aspects of inhibitor development in hemophilia and strategies for clinical management of patients with this complication.

Expert opinion: Research conducted during the last decade has made progress in understanding risk factors for inhibitor development, including identification of genetic risk factors. The ability to calculate a risk score using a child’s genetic profile to predict the likelihood of inhibitor development prior to starting replacement therapy is quite a way off. The so-called ‘Danger Theory’ posits that challenges to the body and immune system increase inhibitor risk. Examples of these challenges are surgery and intense clotting factor treatment. Despite difficulties in the design and performance of studies of a rare disease, and the high cost of treatment, a substantial body of knowledge has accumulated regarding hemophilia A. Basic and clinical research needs to continue even more aggressively than before with special focus on hemophilia B.

Acknowledgment

The authors would like to express their gratitude to Sharyne M. Donfield for checking the language of this manuscript.

Declaration of interest

E Berntorp declares consultancy, paid lectures and participation in advisory boards for Bayer, Baxalta, CSL Behring, Biogen Idec, Octapharma, Pfizer, Sobi and Novo Nordisk, and has received research grants from Bayer, Baxalta, Biogen Idec and Sobi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.