Refractory Wegener's granulomatosis: a model for shorter immunotherapy of autoimmune diseases.
BACKGROUND
Humanised monoclonal antibodies are immunomodulatory tools with high specificity and sustained therapeutic potential. We investigated the effectiveness of treatment with monoclonal antibodies to lymphocyte CD52 and CD4 in patients with Wegener's granulomatosis that had proved intractable despite conventional treatment. We also investigated whether repeated courses of monoclonal antibody treatment alone could be used to control relapses in patients in remission.


METHODS
We studied 17 consecutive patients with refractory Wegener's granulomatosis seen between June 1992 and June 1996. In all patients, treatment with prednisolone and cyclophosphamide or azathioprine for at least six months 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 whole-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 (programmed withdrawal of drug treatment with no return of refractory disease) was obtained in 16 patients after one course of CD52 +/- CD4, and 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 relapses occurred in nine. Monoclonal antibodies alone controlled these during follow-up that totalled 30 patient years. Neither systemic opportunistic infection nor lymphoma development complicated this regimen.


CONCLUSIONS
Monoclonal antibody treatment may be better and safer for diseases, such as Wegener's granulomatosis, that require long-term cytotoxic and steroid treatment because it speeds remission and avoids the iatrogenic complications of cumulative drug toxicity.
Lockwood
C M
CM
University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm; D001327:Autoimmune Diseases / Q000628:therapy*; D015704:CD4 Antigens / Q000276:immunology; D000074301:CD52 Antigen; D006023:Glycoproteins / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000628:therapy*; D006801:Humans; D012074:Remission Induction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015704:CD4 Antigens; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins