Current view and outcome of ITI therapy - A change over time?

Abstract

Introduction: Inhibitor development in people with haemophilia is a serious complication that may require intensive and costly interventions. The goal of inhibitor management should be permanent inhibitor eradication through immune tolerance induction (ITI), but well-designed studies are lacking and the management of patients is therefore defined by the experience and views of the clinician.

Objectives: To explore the current clinical practice and outcome of ITI therapy in Europe and how this may have changed over the last decade, as well as to provide consensus recommendations to guide clinicians in their clinical practice.

Methods: A survey was conducted among 16 European haemophilia comprehensive care centres to evaluate current ITI treatment regimens and success rates in severe and mild/moderate haemophilia A and haemophilia B. In addition, an updated literature review was performed as guidance for providing recommendations.

Results: We demonstrated successful inhibitor treatment in 86% of severe haemophilia A patients with low responding (LR) and 59% of patients with high responding (HR) inhibitors. Some new trends in the management of patients with inhibitors were identified, including a tendency to use low-dose regimens (<50IU/kg/d) in both children and adults with HR inhibitors possibly based on similar success rates demonstrated in the I-ITI study compared to a high-dose protocol. Data on ITI therapy in mild and moderate haemophilia as well as haemophilia B were limited.

Conclusions: The outcome of ITI therapy seems to be stable over time, and treatment regimens remain heterogeneous. The use of low dose regimens however is considered more frequently.

Keywords: Haemophilia; ITI regimens; Immune tolerance induction; Immunosuppression; Inhibitors.