Immune tolerance in hemophilia with factor VIII inhibitors: predictors of success

Background and Objectives. Longterm administration of high doses of factor VIII (FVIII) was shown to eliminate alloantibodies to FVIII (FVIII inhibito rs). This procedure is widely referred to as immune tolerance (IT). Design and Methods. In 1989 an international registry of IT protocols was c reated which recruited 314 patients with severe hemophilia A (HA) and an in hibitor who were given IT treatment. Results. Fifty hemophilia care centers worldwide contributed data to the re gistry; 94.8% of the patients were high responders. The median inhibitor ti ter prior to IT (pre-titer) was 7 BU (range 0-720). The FVIII doses ranged from < 50 International Units (I.U.)/kg/b.w./day to > 200. At the end of IT , 140 patients had undetectable inhibitor titers, including 128 who also ha d normal FVIII kinetics. The remaining 174 patients included 66 with treatm ent failure, 23 who achieved partial responses, 48 patients in whom treatme nt was ongoing and 37 with data inadequate to evaluate outcome. Using logis tic regression, the best predictive model for success included maximum inhi bitor titer, pre-titer, dose and age at treatment FVIII dose and pre-titer were also associated with treatment duration, as was the time between inhib itor detection and treatment. The risk of relapse was approximately 15% aft er 15 years of follow-up. Interpretation and Conclusions. This study underscores the importance of st arting IT as early as possible, at the lowest inhibitor titer and with high FVIII doses in order to maximize the chance of treatment success and minim ize treatment costs. (C) 2001, Ferrata Storti Foundation.