Anti-CD20 therapy of treatment-resistant Wegener's granulomatosis: favourable but temporary response

Rituximab is a genetically engineered chimeric monoclonal immunoglobulin (Ig) G(1) antibody. It binds the CD20 trans-membrane surface antigen expressed by mature B cells but not by antibody secreting plasma cells, and removes the cells by activating complement, inducing cell-mediated lysis, ? and by apoptosis ( 1, 2). Mainly used for the treatment of non-Hodgkin's lymphomas, rituximab has recently been tried with favourable responses in rheumatoid arthritis, systemic lupus erythematosus, and other chronic immunological diseases ( 3 - 6). Wegener's granulomatosis (WG) is a granulomatous vasculitis with high morbidity and mortality ( 7, 8). It is thought that anti-neutrophil cytoplasmatic antibodies ( ANCA) with specificity for proteinase 3 ( PR3) are possibly involved in the pathogenesis of the disease ( 9, 10). Conventional therapy with cyclophosphamide and corticosteroids generally succeeds in inducing remission, but relapses frequently follow. Among the biological agents, tumour necrosis factor-alpha (TNF-alpha) inhibitors have been tried with some success ( 11). Based on a case report ( 12) we recently treated three refractory WG patients with rituximab and achieved almost complete but temporary remission. CD20+ cells disappeared rapidly in peripheral blood, only to rise prior to subsequent disease flares occurring at 34, 63, and 54 weeks, respectively ( Figure 1). A new flare occurred in one patient at 86 weeks. At the end of the observation periods ( 54, 102, and 120 weeks), only one patient had proteinuria. Chest radiographs became normal in two patients, while infiltrates remained unchanged in the third. Granulomatous retro-orbital or sinus masses in two patients seemed unresponsive to therapy.