International workshop on immune tolerance induction: consensus recommendations¹

Abstract

Summary. Although immune tolerance induction (ITI) has been used for 30 years to eliminate inhibitors and restore normal factor pharmacokinetics in patients with hemophilia, there is a paucity of scientific evidence to guide therapeutic decisionmaking. In an effort to provide direction for physicians and hemophilia treatment center staff members, an international panel of hemophilia opinion leaders met to develop consensus recommendations for ITI in patients with severe and mild hemophilia A and hemophilia B. These recommendations draw on the available published literature and the collective clinical experience of the group and are rated based on the level of supporting evidence .

Clinical Characteristics and Prognostic Factors in Hemophiliacs with Intracranial Hemorrhage: A Single-Center, Retrospective Experience

“…The patients' first clotting factor exposure at a high dose was thought to have contributed to inhibitor development. The only proven strategy for eradicating inhibitors and achieving antigen-specific tolerance to clotting factors is ITI [18,19]. ITI involves the repeated administration of FVIII concentrates over a period of weeks to years, with the goal of inducing antigen-specific tolerance [20].…”

Optimizing management of immune tolerance induction in patients with severe haemophilia A and inhibitors: towards evidence‐based approaches

“…Immune tolerance induction (ITI) by means of regular and prolonged administration of FVIII concentrates is currently the only strategy proven to eradicate persistent HR inhibitors (DiMichele et al, 2007). High success rates (60-80%) have been reported with heterogeneous treatment regimens .…”

“…Moreover, economic implications of such a complication are strikingly relevant (Gringeri et al, 2003). Restoring FVIII treatment efficacy is therefore a leading objective after inhibitor diagnosis, especially in children (Gringeri & Mannucci, 2005;Astermark et al, 2006c;Hay et al, 2006;DiMichele et al, 2007), because resuming FVIII prophylaxis they may preserve healthy joints long-term (Manco-Johnson et al, 2007).…”

“…In this scenario, with the aim at providing useful information to haemophilia treaters, an European board (Astermark et al, 2006c) and more recently, an international panel of haemophilia opinion leaders (DiMichele et al, 2007) developed consensus recommendations for ITI on the basis of the available published literature and the collective clinical experience of the groups. Recommendations were rated based on the level of supporting evidence, being in most cases the lowest (IV), and only for some issues reaching level IIb.…”

“…However, tolerance had been defined by normalization of FVIII recovery and half-life in only one of these patients (DiMichele & Kroner, 2002). Clinical and laboratory criteria for assessing ITI outcome proposed for the I-ITI study were established by consensus at the Second International Conference on ITI and recently revised (Table III; DiMichele et al, 2007).…”