IMMUNOTHERAPY IN MULTIPLE-SCLEROSIS .1.

The efficacies of corticosteroids and azathioprine (part 1) and of cyc lophosphamide, immune globulin, cyclosporine, interferons, copolymer 1 , and cladribine (part 2) in patients with multiple sclerosis (MS) are reviewed. MS is an inflammatory, demyelinating disease of the CNS tha t commonly affects young adults. The involvement of various immune mec hanisms in MS suggests a role for immunomodulating therapy. The goals of immunotherapy vary with the clinical stage of the disease and inclu de (1) improving recovery from exacerbations, (2) decreasing the numbe r or severity of relapses, (3) preventing the development of chronic p rogressive disease from a relapsing-remitting course, and (4) decreasi ng further progression in patients with chronic progressive disease. I n clinical trials, corticotropin and corticosteroids have been found t o accelerate recovery from exacerbations. Tapering is of ten effective after high-dose induction therapy. Long-term maintenance regimens do not alter disease progression and are not recommended. Azathioprine pr oduces modest benefits with respect to relapse rates and disease progr ession after two or more years of treatment; adverse effects are mild to moderate. Azathioprine should not be used in patients with aggressi ve disease who may approach severe disability in 6-18 months. Cyclopho sphamide, because of its modest impact on disease progression and its potentially severe adverse effects, including cancer, should be reserv ed for patients with aggressive relapsing-remitting or chronic progres sive disease in whom other treatments have failed to work; maintenance therapy is necessary after induction. Intravenous immune globulin may benefit patients with severe relapses; however, its efficacy remains unproven. Cyclosporine also cannot be recommended because of its modes t efficacy, marked adverse effects, and high cost. Interferon beta-lb is a more specific immunotherapy that has been found to decrease the n umber and severity of relapses. This treatment should be considered in patients with relapsing-remitting disease who are having two or more exacerbations per year. Copolymer 1 and cladribine have shown some pro mising early results. Although various immunotherapeutic drugs can pro vide relief in patients with MS, none is capable of reversing disease progression, and some can cause serious adverse effects. Better unders tanding of the immunologic basis of MS may lead to more specific immun otherapies with more lasting benefits.