Efficacy of rituximab in limited Wegener's granulomatosis with refractory granulomatous manifestations.

OBJECTIVE: Patients with limited Wegener's granulomatosis (WG) 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.

RESULTS: Four men and 4 women with limited WG were treated with rituximab. Patients' mean age was 39 years. All patients had predominantly necrotizing granulomatous disease manifestations, including chronic sinusitis, pulmonary nodules, orbital pseudotumor, and subglottic stenosis. Patients had failed an average of 3 immunosuppressive agents, not including glucocorticoids. Six patients had failed (or were intolerant of) therapy with cyclophosphamide; all 8 had failed therapy with methotrexate. At the time of treatment, 3 of the 8 patients were antineutrophil cytoplasmic antibody-negative. Rituximab successfully induced disease remission in all 8 patients. Three patients were retreated preemptively with rituximab after return of peripheral blood B-cells. Five patients were successfully retreated with rituximab after disease flare.

CONCLUSION: Rituximab is an effective therapy for patients with limited WG and may be sufficient to induce sustained remission, even among patients with refractory disease and predominantly necrotizing granulomatous disease manifestations.