Immunosuppressive drugs in multiple sclerosis

Corticotropin, adrenal cortical steroids, alkylating agents, and antimetabolites are being used to treat multiple sclerosis (MS). The benefits of these substances must be carefully weighed against the risks. While the steroids appear to improve neurologic function lost in acute relapses, they do not affect progression. They may increase the frequency of relapses or predispose patients to earlier relapses than expected during the natural course of the illness. The alkylating agent cyclophosphamide appears to temporarily improve neurologic function, decrease spinal fluid immunoglobulin, and prevent progression. Cancer of the bladder and leukemia are serious long-term risks in a young population. Chlorambucil appears relatively ineffective and leukemogenic. Relapse rate and progression are most likely ameliorated by several years9 treatment with the antimetabolite azathioprine. The long-term risks to the patient and his or her children are unknown. Controlled clinical trials of 5 to 10 years9 duration with even longer follow-up will be necessary to delineate risk and benefit. No factors that will predict response to the drugs are known. Since the immunosuppressive drugs will probably be required for life in many patients, we may be faced with a choice between control of symptoms and signs at age 30 or increased risk of cancer at age 60.