TREATMENT OF REFRACTORY WEGENERS GRANULOMATOSIS WITH HUMANIZED MONOCLONAL-ANTIBODIES

Conventional immunosuppression for systemic vasculitides is limited by substantial side-effects, cumulative drug toxicity and refractoriness in some patients. Six Wegener's granulomatosis patients who had been refractory to conventional therapy for at least 6 months, were treated with humanized monoclonal antibodies specific to lymphocyte CD52 or C D4 antigens. Diagnosis was on clinicopathological grounds, supported b y the presence of autoantibodies to Proteinase 3. Histological evidenc e of persistent disease activity was obtained for each patient, Humani zed monoclonal anti-CD52, with or without anti-CD4, was given intraven ously up to 40 mg/day for up to 10 days. Remission, (programmed withdr awal of drug therapy without return of refractory disease) was achieve d in all patients. Cytotoxic drugs were discontinued at the time of mo noclonal antibody treatment and not used again; steroids were withdraw n gradually. Four patients relapsed at 1.5, 5, 10 and 18 months, and w ere treated successfully with further monoclonal antibody therapy alon e. Three years after the study began, five patients are well; one pati ent died at surgery whilst in remission. Humanized monoclonal antilymp hocyte antibodies may provide an effective treatment in patients with systemic vasculitis which is refractory to steroids or cytotoxic agent s, or who are intolerant of these drugs.