Epidemiology of inhibitor development in haemophilia A patients treated with virus-inactivated plasma-derived clotting factor concentrates.

The development of neutralising antibodies against factor VIII (FVIII) or factor IX (FVIX) is one of the most serious complications in the treatment of haemophiliacs. The reported frequency of inhibitor development ranges widely and is affected by several variables in study design and study population. Five former studies and six recent previously treated patient (PUP) studies were analysed and compared. In all studies the patients received one virus inactivated plasma derived clotting factor concentrate. Former studies mostly considered the prevalence of inhibitor development, thus underestimating its true risk. Prevalence ranged between 7 and 18% [3, 4, 7, 9, 10]. Six recent, mostly prospective PUP studies on inhibitor incidence revealed inhibitor formation in between 22.3-33% in severe and moderate haemophiliacs. Inhibitor development occured after a median of 11-46 exposure days (ED) at a median age of between 1.7 and 3.3 years [5, 6, 8, 11-13, 18, 19].