Presentation: Efficacy of Rituximab in Limited Wegener’s Granulomatosis with Refractory Granulomatous Manifestations (2007)

2009 Efficacy of Rituximab in Limited Wegener’s Granulomatosis with Refractory Granulomatous Manifestations

PURPOSE: Limited Wegener’s granulomatosis (WG) is frequently treated with a combination of glucocorticoids and methotrexate. Patients with limited WG, however, may experience a relapsing and remitting course. How such patients should be treated--particularly when they are refractory to standard-of-care therapies--is not clear. Rituximab is a monoclonal anti-CD20 antibody that has been used successfully to treat multiple forms of autoimmune and rheumatic diseases, but its role in the treatment of limited WG remains uncertain.
METHODS: Eight patients with limited WG who were refractory to (or intolerant of) standard immunosuppressive therapies were evaluated at the Johns Hopkins Hospital or the Mayo Clinic Rochester, and were treated with rituximab using a standard lymphoma protocol (i.e., 375 mg/m2 weekly for four weeks).
RESULTS: Four men and 4 women with limited WG were treated with rituximab. The mean age of the patients was 39 years (range: 19 to 58 years old). Seven patients had chronic sinusitis; in addition, 5 of the 8 patients had other granulomatous manifestations of Wegener’s, including pulmonary nodules, orbital pseudotumor, and subglottic stenosis. Patients had failed an average of 3 immunosuppressive agents, not including glucocorticoids (range: 1 to 6). Six patients had failed (or were intolerant of) therapy with cyclophosphamide; all 8 had failed therapy with methotrexate. At the time of treatment, 4 of the 8 patients were ANCA negative. Rituximab successfully induced prolonged disease remission in all 8 patients. Three patients were re-treated preemptively with rituximab after return of peripheral blood B-cell levels. Four patients were successfully re-treated with rituximab after disease flare (which occurred a mean of 13 months after the first treatment with rituximab, and 3 months after B-cell reconstitution).
CONCLUSIONS: Rituximab is an effective therapy for patients with limited Wegener’s granulomatosis, and may be sufficient to induce prolonged remission, even among patients with refractory disease and predominantly necrotizing granulomatous disease manifestations.

 P. Seo, None; U. Specks, None; K.A. Keogh, None.