Induction of Immune Tolerance in Haemophilia A Inhibitor Patients by the Bonn Protocol: Predictive Parameter for Therapy Duration and Outcome

The treatment of inhibitors is one of the most challenging fields in haemophilia care. The present study reports the results of 60 haemophilia A inhibitor patients treated according to the 'Bonn Protocol' and evaluates predictors for the duration and outcome of therapy. Successful immune tolerance could be achieved in 52 patients (86.7%) while the therapy failed in eight patients (13.3%). The immune tolerance achieved was longlasting in all 52 patients, with no inhibitor relapse in up to 20-years follow-up. The course of ITT was influenced by several factors. Interruptions of treatment during the ITT course led to a substantial prolongation of ITT duration (median 39.9 months vs 14.1 months in continuously treated patients). Infections of intravenous central lines appeared to be frequently coincided with ITT prolongation and sometimes even ITT failure. Further negative predictors towards the ITT duration were high inhibitor titres at enrollment or during ITT. There was also a tendency towards longer ITT duration in patients exhibiting the prevalent intron 22 inversion. As a consequence of our data treatment interruptions and infections of intravenous central lines should be avoided during the course of ITT. Furthermore our data suggest, that ITT should be started at low inhibitor titres preferably with a high factor VIII dosage protocol.