Immune tolerance induction for the eradication of inhibitors in patients with hemophilia A

Abstract

Background: Both genetic and environmental factors contribute to the formation of alloantibodies that bind to functional domains on the Factor VIII (FVIII) molecule and inhibit its function. Patients with hemophilia A who develop high-titer inhibitors are at increased risk for serious hemorrhage and disability, particularly arthropathy, because bleeding events do not respond to standard therapy. Immune tolerance induction (ITI) is usually attempted to eradicate newly diagnosed inhibitors, restore replacement FVIII pharmacokinetics, and improve bleed management and quality of life. Objective: This paper summarizes regimens used for ITI, predictors of success and failure, and adjunctive therapies for patients failing ITI therapy. Methods: This is a systematic review of published reports on ITI regimens, data from registries capturing response rates and predictors of success, and reports of adjunctive treatments used to enhance ITI therapy. Results/conclusion: Many issues remain unresolved, chief among them optimal dose and dosing regimen, choice of FVIII product, and the role of adjunctive therapy. Resolution of these issues, as well as new approaches to inhibitor management, may come from ongoing basic science research and clinical trials.

Keywords::

• Factor VIII
• hemophilia
• immune tolerance induction
• inhibitors