A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis

Abstract

Objective. To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV).Methods. Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months.Results. Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ؎ SD of 11.9 ؎ 5.4 at baseline to 7.1 ؎ 5.7 at month 2; P < 0.001) up to month 24 (4.4 ؎ 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated.Conclusion. RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.Mixed cryoglobulinemia, which is also known as cryoglobulinemic syndrome or cryoglobulinemic vasculitis (CV), is a systemic vasculitis that is primarily mediated by immune complexes and is associated with hepatitis C virus (HCV) infection and B cell lymphoproliferation (1-5). HCV infection might be crucial for

Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases

“…This trial compared RTX (without or with low-dose steroids) to a conventional immunosuppressive treatment including corticosteroids, cyclophosphamide, azathioprine, or plasma exchange. This trial documented the superiority of RTX over standard therapy [54]. Duration of response to RTX of MC manifestations is difficult to define due to the lack of long-term follow-up data in most studies.…”

Hepatotropic Viral Infection Associated Systemic Vasculitides—Hepatitis B Virus Associated Polyarteritis Nodosa and Hepatitis C Virus Associated Cryoglobulinemic Vasculitis

“…69 Two randomized controlled trials published recently, have shown the efficacy of rituximab as compared to conventional therapy. 70,71 Role of expansion of T regulatory (Treg) cells with subcutaneous IL 2 injections and associated clinical improvement in patients with refractory HCV associated CV may suggest that low dose IL2 may promote tolerance but we will have to wait for further studies. 72 In future, other anti B cell targeted therapies like ocrelizumab and ofatumumab (anti CD20), epratuzumab (anti CD22) and belimumab (anti BAFF) might also prove useful in management of severe systemic/refractory manifestations.…”

B cell activating factor (BAFF) in the natural history of chronic hepatitis C virus liver disease and mixed cryoglobulinaemia

“…It is possible that factors such as cytokines, growth factors and host genetic background may also link chronic HCV infection and lymphoproliferation [8,9].…”