Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response

Abstract

Immune tolerance induction (ITI) is effective in approximately 70% of haemophilia patients with inhibitors. Poor prognostic factors are age >6 years, ITI started >1 year from inhibitor development, inhibitor peaks >200 BU, inhibitor titre >10 BU when ITI is started and previously failed ITI. The objective of this study was to identify the effectiveness in ITI of a high purity von Willebrand factor/factor VIII (VWF/FVIII) complex concentrate in inhibitor patients at high risk of failure. Patients with severe or moderate haemophilia A and high responding inhibitors who had at least one poor prognostic factor for ITI failure were prospectively followed-up. Success was defined by undetectable inhibitor, recovery and half life >66% of expected values. ITI dose regimens were chosen by each haemophilia centre. Seventeen haemophiliacs (16 severe, one moderate), aged 4-54 years (median 23) were followed-up for 6-71 months. Poor prognostic factors were delayed-onset ITI (n = 16), age >6 years (n = 16), previously failed ITI (n = 4), inhibitor peak >200 BU (n = 2) and inhibitor >10 BU when ITI was started (n = 4). Complete success was obtained in nine patients (53%) after 4-30 months of treatment (median 24), including two of four patients who had previously failed ITI. Seven patients achieved a partial success, with sustained low inhibitor titres (median 1.5 BU, range 1.1-2.8) but abnormal recovery and/or half-life, while the remaining patient withdrew ITI after 12 months when the inhibitor titer was still 70 BU. These findings suggest that high purity VWF/FVIII complex concentrates are effective in ITI, even in patients at high risk of failure.