Rituximab for autoimmune haemophilia: a proposed treatment algorithm

Abstract

We previously reported durable complete responses following brief courses of rituximab and prednisone with or without cyclophosphamide in four patients with autoimmune haemophilia and inhibitor titres of 5-60 BU. We report here responses to this monoclonal anti-CD20 antibody in four additional patients, including two patients with inhibitor titres >200 BU. Factor VIII levels became normal 2-35weeks after 4 or 8 weekly doses of rituximab, brief courses of prednisone and in one patient immunoglobulin. Complete responses are ongoing at 10 months in two patients. Two patients relapsed: a patient whose initial inhibitor titre was 525 BU relapsed at 3.5 months and a long-term prednisone-dependent patient at 8.5 months. Both responded to second courses of rituximab and prednisone and are in remission. Our experience suggests that rituximab is a safe and effective addition to immunosuppression with prednisone and cyclophosphamide to treat autoimmune haemophilia, and may permit early discontinuation or even avoidance of these potentially toxic agents. High-titre inhibitor patients, however, may require multiple courses of rituximab or the addition of cyclophosphamide. Pending randomized studies, we propose an algorithm based on our experience and other reports for incorporating rituximab in the treatment of this rare disorder.

Rituximab in the treatment of autoimmune haematological disorders

“…Six patients who initially responded to rituximab treatment but who subsequently relapsed responded to rituximab re-treatment, achieving sustained remissions Aggarwal et al, 2005;Field et al, 2007).…”

“…Although singleagent rituximab can treat acquired haemophilia rapidly and effectively in many cases, patients with high autoantibody titres may only achieve partial responses or may attain a complete response only very slowly (Table III). However, improved responses can be achieved by increasing the number of doses of rituximab or by combining rituximab with cyclophosphamide and/or corticosteroids Aggarwal et al, 2005). The time taken to achieve a response with rituximab ranged from 1 to 65 weeks (Table III).…”

“…Moreover, in young female patients, such treatment can compromise fertility (Maillard et al, 2006). In contrast, rituximab was well tolerated with few side effects and no infectious complications reported in patients with acquired haemophilia (Wiestner et al, 2002;Fischer et al, 2003;Jy et al, 2003;Stasi et al, 2004;Aggarwal et al, 2005;Clatworthy & Jayne, 2006;Maillard et al, 2006;Santoro et al, 2007), and was an effective alternative for patients unable to receive cytotoxic therapy (Jy et al, 2003;Marietta et al, 2003;Stasi et al, 2004;Berezné et al, 2006;Maillard et al, 2006). Aggarwal et al (2005) have proposed an algorithm for the treatment of autoimmune haemophilia.…”

Rituximab for the treatment of acquired antibodies to factor VIII

“…All together we were able to identify ten published articles or short reports, [15][16][17][18][19][20][21][22][23][24] eight abstracts [25][26][27][28][29][30][31][32] and one unpublished observation. 33 These reports presented the results of treatment with rituximab in a total number of 43 patients.…”

Acquired Factor VIII Inhibitors: Pathophysiology and Treatment

“…"Off label" use of rituximab has been studied in acquired hemophilia, showing promising results of durable remission. 34,[54][55][56][57][58][59][60] The usual dose is 375 mg/m 2 each week for 4 weeks. Most responses are seen within the first 2 weeks of therapy, and the general consensus is that it should be considered in pa-tients who are resistant to first-line therapy or cannot tolerate standard immunosuppressive therapy.…”