First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study. (23rd July 2015) - Kreuz, W.
Abstract : Introduction/background: Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. Aim: The ongoing, international, open‐label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors. Patients/methods: Forty‐eight prospective patients in this interim analysis received a single plasma‐derived, von Willebrand factor‐stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start (<5 BU) received 50–100 IU FVIII kg −1 daily, or every other day; 'high responders' (≥5 BU) received 100 IU FVIII kg −1 every 12 h. Results: Forty of 48 patients (83.3%), had at least one risk factor for poor ITI‐prognosis at ITI start (i.e. age ≥7 years, >2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response ; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success . ITI outcome was significantly associated with inhibitor titre level at ITI start ( P = 0.0068), number of poor prognosis factors for ITI success ( P = 0.0187), monthly bleeding rate during ITI ( P = 0.0005) and peak inhibitor titre during ITI ( P = 0.0007). Twenty‐two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success . Conclusion: Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success.