Rituximab as first‐line treatment for the management of adult patients with non‐severe hemophilia A and inhibitors

Abstract

patients with non-severe hemophilia A and inhibitors. J Thromb Haemost 2014; 12: 897-901.Summary. Background: The role of immunosuppression in the management of patients with congenital hemophilia and inhibitors is uncertain. The use of rituximab has been limited to case reports and case series. In most reports, rituximab was used as second-line or third-line treatment following failure of conventional immune tolerance induction therapy, and more commonly in pediatric patients. Objectives: The objective of this study was to describe our experience with rituximab for the eradication of factor VIII inhibitors in adult patients with non-severe hemophilia A. Patients: We retrospectively reviewed the medical records of adult patients with non-severe hemophilia A and a diagnosis of FVIII inhibitor treated with rituximab (four weekly doses of 375 mg m À2 ) as first-line treatment at our hemophilia center. Results: We identified nine consecutive adult patients with hemophilia A (moderate, n = 5; mild, n = 4) at our institution between 2000 and 2013, with a median age of 54 years (range, 24-77 years) at the time of inhibitor diagnosis. No patient received concomitant immune tolerance induction therapy. All nine patients had successful eradication of FVIII inhibitors. The median time from the first dose of rituximab to a clinical response was 95 days (range, 12-278 days). The median follow-up was 56 months (range, 13-139 months). Following inhibitor eradication, eight patients were rechallenged with FVIII concentrates. Two patients developed inhibitor recurrence associated with surgery. Conclusion: This case series demonstrates that rituximab is a useful first-line treatment to achieve sustained inhibitor eradication in adult patients with non-severe hemophilia A.

Inhibitors in haemophilia A and B: Management of bleeds, inhibitor eradication and strategies for difficult‐to‐treat patients

“…Nevertheless, in the INSIGHT study (International Study on Etiology of Inhibitors in Patients with a Moderate or Mild Form of Hemophilia A, Influences of Immuno‐Genetic & Hemophilia Treatment Factor), which included 101 non‐severe patients with haemophilia A and inhibitors, inhibitors disappeared in the majority of patients (72/101; 72%), either spontaneously (51/73; 70%), or after eradication treatment (21/28; 75%) . In patients with mild haemophilia A, FVIII inhibitors may share features with FVIII autoantibodies that occur commonly in acquired haemophilia A, and this may explain why immunosuppressive therapy can be effective in reducing the inhibitor titre in some patients …”

Management of adult non‐severe haemophilia A patients with inhibitors: a practice‐pattern survey

“…In a systematic review of 49 haemophilia patients with inhibitors, rituximab appeared to be more effective in NSHA patients when administered concomitantly with FVIII concentrates [7]. We reported our single-centre retrospective review of nine consecutive patients with NSHA over a 13-year period; this study demonstrated successful use of singleagent rituximab as first-line therapy for inhibitor eradication with sustained success in seven of the nine patients [6].…”

“…Immunosuppressive (IS) drugs, such as corticosteroids and rituximab, either alone or in combination with ITI, have also been used for inhibitor eradication, with inconsistent success rates [4,6,7]. We reported our single-centre retrospective review of nine consecutive patients with NSHA over a 13-year period; this study demonstrated successful use of singleagent rituximab as first-line therapy for inhibitor eradication with sustained success in seven of the nine patients [6]. We reported our single-centre retrospective review of nine consecutive patients with NSHA over a 13-year period; this study demonstrated successful use of singleagent rituximab as first-line therapy for inhibitor eradication with sustained success in seven of the nine patients [6].…”

“…Limited data are available on ITI in patients with NSHA, although in general, this approach appears to be less effective than in SHA [4,5]. Immunosuppressive (IS) drugs, such as corticosteroids and rituximab, either alone or in combination with ITI, have also been used for inhibitor eradication, with inconsistent success rates [4,6,7]. In a systematic review of 49 haemophilia patients with inhibitors, rituximab appeared to be more effective in NSHA patients when administered concomitantly with FVIII concentrates [7].…”

Inhibitor screening in non‐severe haemophilia patients; a major challenge

“…However, limited data are available on this regimen in non‐severe haemophilia patients, and this approach appears to be less effective than in patients with severe haemophilia (Kempton et al , ). Immunosuppressive drugs, such as corticosteroids and rituximab, either alone or in combination with immune tolerance introduction, have also been used for inhibitor eradication, but with inconsistent success rates (Kempton et al , ; Lim et al , ). Due to the antibodies neutralising FVIII concentrates, by‐passing agents, such as activated recombinant FVII or activated prothrombin complex concentrates are potential alternatives (Matino et al , ).…”