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.

• Authors: S De Vita, L Quartuccio, M Isola, C Mazzaro, P Scaini, M Lenzi, M Campanini, C Naclerio, A Tavoni, M Pietrogrande, C Ferri, M T Mascia, P Masolini, A Zabotti, M Maset, D Roccatello, A L Zignego, P Pioltelli, A Gabrielli, D Filippini, O Perrella, S Migliaresi, M Galli, S Bombardieri, G Monti
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 64 Issue 3 Pg. 843-53 (Mar 2012) ISSN: 1529-0131 [Electronic] United States
• PMID: 22147661 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 by the American College of Rheumatology.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Antiviral Agents
• Glucocorticoids
• Immunologic Factors
• Rituximab
• Cyclophosphamide
• Azathioprine

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Murine-Derived (therapeutic use)
• Antiviral Agents (therapeutic use)
• Azathioprine (therapeutic use)
• Combined Modality Therapy
• Cryoglobulinemia (complications, pathology, therapy)
• Cyclophosphamide (therapeutic use)
• Drug Resistance, Viral (drug effects)
• Drug Substitution
• Drug Therapy, Combination
• Female
• Glucocorticoids (therapeutic use)
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Immunologic Factors (therapeutic use)
• Male
• Middle Aged
• Plasmapheresis
• Remission Induction
• Rituximab
• Severity of Illness Index
• Treatment Outcome
• Young Adult