Immune tolerance induction in hemophilia A: a review

Abstract

In this article, a comparative analysis of the data stemming from the studies conducted in the field of immune tolerance treatment (ITT) of hemophilia A was attempted. Comparisons are difficult because previous studies differ in many respects, including the dosage of factor (F) VIII, the number of FVIII administrations per day, the association with immunosuppressive drugs (prednisone, cyclophosphamide), and, most importantly, the definition of success in terms of the reacquisition of tolerance. However, a number of variables consistently influenced outcome: the inhibitor titer, either the maximum one or the one assayed before immune tolerance (IT) start and age. As to the FVIII dose, results are contrasting, even though the overall impression is that high dosages are associated with higher success rates. Treatment duration analyses appear to be fairly consistent in all the studies, with 1 year as the crucial time period useful in predicting outcome. Preliminary data suggest that concentrates containing von Willebrand factor may increase the success rate and allow patients refractory to IT procedures carried out with ultrapure or recombinant concentrates to become tolerant in the end. These data need to be formally confirmed in trials that compare the different brands. In the studies published so far, a common language and widely accepted definitions of the variables have emerged, which are important in setting up the controlled trials and improving the comparison among published data.