Immune Tolerance for the Treatment of Factor VIII Inhibitors - Twenty Years' 'Bonn Protocol'

Immune tolerance induction for patients with severe hemophilia A: a critical literature review

“…After the first German experience led to define the highdose Bonn protocol (FVIII 200-300 IU/kg daily) [16], the Malmö protocol was developed for achieving rapid responses, particularly in patients with high-titer inhibitors [17], using high-dose daily FVIII infusions in association with i.v. immunoglobulins and cyclophosphamide, together with preliminary extracorporeal immunoadsorption with a protein A Sepharose column if initial inhibitor titre was [10 BU ml.…”

Factor VIII Inhibitors: Risk Factors and Methods for Prevention and Immune Modulation

“…ITI was first reported in 1977 [76] and is currently the most accepted way to treat patients with inhibitors [77]. Most treatments involved high dose infusions (50-200 IU/kg) until Bethesda titers have been reduced or antibodies have entirely disappeared.…”

US Guidelines for immune tolerance induction in patients with haemophilia a and inhibitors

“…The "Bonn protocol" is the prototype from which subsequent ITI regimens evolved. While dosing varies, and aPCC and/or immunomodulation may or may not be included (Table 1) [5][6][7][8][9][10], all regimens use frequent, uninterrupted exposure to FVIII over a period of months to years with the goal of inducing antigenspecific tolerance and normalization of FVIII pharmacokinetics [11].…”

“…Overall ITI success rates reported in retrospective cohort studies, each evaluating 8-37 patients, ranged from 57 to 91% [5][6][7][8][9][10]. However, the value of the findings and the ability to compare results were limited by a lack of standardized treatment, data collection and definitions of tolerance.…”