REFRACTORY WEGENERS-GRANULOMATOSIS - A MODEL FOR SHORTER IMMUNOTHERAPY OF AUTOIMMUNE-DISEASES

Background: Humanised monoclonal antibodies are immunomodulatory tools with high specificity and sustained therapeutic potential. We investi gated the effectiveness of treatment with monoclonal antibodies to lym phocyte CD52 and CD4 in patients with Wegener's granulomatosis that ha d proved intractable despite conventional treatment. We also investiga ted whether repeated courses of monoclonal antibody treatment alone co uld be used to control relapses in patients in remission. Method: We s tudied 17 consecutive patients with refractory Wegener's granulomatosi s seen between lune 1992 and lune 1996. In all patients, treatment wit h prednisolone and cyclophosphamide or azathioprine for at least six m onths had been unsuccessful, and all were followed up for at least six months after monoclonal antibody treatment. Diagnosis was established on clinical, serological and histological criteria. Disease activity in the upper airways, lungs or kidneys at referral was documented by w hole-body scintiscanning, computed tomography, or isotope measurement of the glomerular filtration rate, as well as by tissue biopsy, where appropriate. Monoclonal antibodies to CD52 followed by CD4 were given intravenously in courses lasting five days each. Results: Remission (p rogrammed withdrawal of drug treatment with no return of refractory di sease) was obtained in 16 patients after one course of CD52 +/- CD4, a nd confirmed by serial studies of abnormalities found before treatment . In one patient, disease remained unchecked. In responders, cytotoxic drugs were stopped during monoclonal antibody treatment and were not used again, while steroids were tapered off gradually. Disease relapse s occurred in nine. Monoclonal antibodies alone controlled these durin g follow-up that totalled 30 patient years. Neither systemic opportuni stic infection nor lymphoma development complicated this regimen. Conc lusion: Monoclonal antibody treatment may be better and safer for dise ases, such as Wegener's granulomatosis, that require long-term cytotox ic and steroid treatment because it speeds remission and avoids the ia trogenic complications of cumulative drug toxicity.