Vasculitis
Abstract 1265: Repeated Use of Rituximab in Refractory Wegener’s Granulomatosis: Efficacy for Glucocorticoid-Free Remission Maintenance
Authors: Jason M. Golbin, Karina A. Keogh, Fernando C. Fervenza, Steven R. Ytterberg, Ulrich Specks
Background: Without therapy, the mortality associated with the systemic form of Wegener’s granulomatosis approaches 100%. This changed radically in the 1970s with the introduction of cytotoxic agents such as cyclophosphamide. The so-called Fauci-Wolff protocol dramatically improved the immediate mortality associated with this diagnosis, but at a considerable cost. The regimen of cyclophosphamide and high-dose glucocorticoids that has become standard is associated with an unacceptably high level of untoward events, including infertility, hemorrhagic cystitis, and accelerated osteoporosis. For this reason, recent work has turned towards developing alternatives to cyclophosphamide. One such promising compound is rituximab, a B-cell specific monoclonal antibody that is now the subject of a multinational randomized controlled trial (Rituximab in ANCA-associated Vasculitis, or RAVE). Because this monoclonal antibody is not fully humanized, it has not been clear if rituximab might lose efficacy after repeated doses.
Study Design: Retrospective analysis of patients diagnosed with Wegener’s granulomatosis who were treated with at least 2 courses of rituximab at the Mayo Clinic between January 2000 and December 2005. All patients were either refractory to cyclophosphamide, or had contraindications to treatment with cyclophosphamide. A standard lymphoma protocol (i.e., 375 mg/m2 weekly for four weeks) was used.
Results: Twenty-one patients were included in this study, all of whom were PR3-ANCA positive prior to therapy, and had a mean age of 47 years. On average, patients had received approximately 3 courses of rituximab over 3 years. Relapse occurred only after reconstitution of B-cells; patients who were retreated preemptively after return of detectable B-cells did not experience disease flare. IgG levels did not decline significantly over time, and no increase in the severity or frequency of infections was noted.
Editorial Comments: This group has previously reported their success using rituximab for the treatment of Wegener’s granulomatosis in patients who had contraindications to cyclophosphamide use. This abstract updates their previous findings, and indicates that use of prolonged B-cell suppression may be a safe and effective strategy for the long-term treatment of patients with Wegener’s granulomatosis. It is important to examine this data in context; enthusiasm for the use of etanercept for the treatment of Wegener’s granulomatosis was similarly sanguine, only to be refuted by a large, randomized clinical trial (WGET). Moreover, while many case reports support the use of rituximab for the treatment of severe Wegener’s granulomatosis, its utility for the treatment of the limited form of this disease—which primarily consists of granulomatous disease of the sinuses and respiratory tract—remains controversial