A review of systemic nonspecific immunosuppressive treatment of multiple sclerosis

This article is a critical review of the literature about the effects of systemic immunosuppression on patients with multiple sclerosis. Azathioprine (or 6-mercaptopurine), chlorambucil, cyclophosphamide, levamisole, melphalan, podophyllin and other drugs by themselves and in combination therapies with adrenocortical steroids, thoracic duct drainage, and antilymphocyte sera or globulins are discussed. A decrease in frequency of relapses, rate of progression, cerebrospinal fluid gamma globulin and oligoclones, and in cerebrospinal fluid pleocytosis can be achieved, at least temporarily, by certain treatments. Lack of appropriate controls makes it difficult to evaluate these results. Therefore, immunosuppressive therapy of multiple sclerosis should be considered highly experimental. Systemic immunosuppression is difficult to achieve and maintain, has a high incidence of side effects, and the long-term consequences are not well established. More studies of drug combinations, with stratification of patients and with follow-up observations for at least 5 years, will be necessary before firm conclusions can be reached. Controlled studies of cyclophosphamide or azathioprine might be started now but other modalities also might be used in exploratory or pilot studies. These studies will require a significant investment by patients, biomedical personnel, and funding agencies, and should not be entered into casually.