Rituximab for Treatment of Hemophilia A with High-Responder Inhibitors

Background: The development of inhibitors is a complication factor replacement therapy in hereditary factor VIII deficiency. Several management options are available for the treatment of inhibitor. Rituximab, a monoclonal antibody against CD20, reduces inhibitor level in rare bleeding disorders. The aim of this study was to evaluate the effectiveness of rituximab in lowering or eliminating the levels of factor VIII inhibitors in patients with severe hemophilia A. Materials and Methods: This cross sectional study was conducted on ten male patients with severe hemophilia A with inhibitor titer ≥5 Bethesda Units/ml (BU) during 100 weeks in comprehensive hemophilia care center in Imam Khomeini Hospital. The recruitment period began in September 2010 and continued through November 2012. Patients received rituximab 375 mg/m² weekly from week 1 through 4. Inhibitor titer was measured monthly on week 6 to 22, Then on week 24, 36, 52, and 100. All patients received four doses of rituximab. Results: Major response occurred on four patients (40%).Three patients had a minor response and three patients with no response to treatment. Adverse events were included renal impairment, headache and increase liver transaminase. No severe allergic reaction was observed. Conclusion: Rituximab is useful for eradication or lowering inhibitor titer in severe hemophilia A with high-titer inhibitor. Further clinical trials studies need to evaluate efficacy and safety of the rituximab as an adjunctive therapy in combination immune tolerance induction strategies.