Treatment of an Adult Patient with Hemophilia A and High Titer Inhibitor with Rituximab and Prednisone.

Abstract

Development of inhibitors is a serious complication in hemophilia A patients (factor VIII deficiency) who receive plasma-derived or recombinant products. It occurs in about 20–30% of patients with severe or moderate hemophilia A. The presence of a high titer inhibitor (titer > 5BU), is associated with increased morbidity and mortality, complicates disease management, and increases cost of treatment. Treatments used for the management of acute bleeds include high doses of human FVIII, porcine FVIII, prothrombin complex concentrates, FVIII bypassing activity (FEIBA), and recombinant VIIa (rVIIa)). The induction of immune tolerance (IT)with daily high doses of FVIII has been reported to eradicate the inhibitor in 60–80% of patients; although it is a very costly procedure, the response appears to be dependent on the level of the inhibitor with patients with low inhibitor titer (<10 BU) responding better to IT treatment. To rapidly reduce/eradicate the alloimmune factor VIII antibodies immunomodulatory agents, including immunoglobulin, corticosteroids, cyclophosphamide, azathioprine, and plasmapheresis have been used. Rituximab, an anti-CD20 monoclonal antibody, eliminates circulating B cells and has been shown to reduce/eradicate alloimmune factor VIII antibodies in children with severe hemophilia A. We report the clinical course and response to rituximab treatment in a 24 year old male with moderate hemophilia A and high titer inhibitor. The patient presented with a massive retroperitoneal bleed with Hb 6.4g/dL and an inhibitor titer of 41 BU reaching a maximum of 111 BU over the next four weeks. For the acute bleeding episode, he received FEIBA and rVIIa. For the treatment of inhibitor, he was given rituximab 375 mg/m2 × 4 together with prednisone 1 mg/Kg daily. Prednisone was slowly tapered off over the next several weeks. Three months later, his inhibitor titer had decreased to 35 BU and remained below 15 BU for the next 30 weeks. The course of this patient's response suggests that rituximab in combination with prednisone may rapidly reduce inhibitor titer in adult patients with hemophilia and high titer inhibitor. It is possible the rituximab therapy may replace IT therapy or be used as an adjunct to IT therapy. Also, the combination of rituximab and prednisone treatment may reduce/prevent the exposure of young patients to cytotoxic chemotherapy. Randomized clinical trials will be required to determine whether the combination of rituximab and prednisone is a better option compared to cytoxan and prednisone to reduce/eradicate inhibitors in young adult hemophilia patients with high titer inhibitor. [Display omitted]