Current disease-modifying treatment of multiple sclerosis.

The treatment era for multiple sclerosis began in 1993 with the approval of the first disease-modifying therapy. This changed the management of multiple sclerosis from treating acute exacerbations to focusing on preventive therapeutic options that lessen the risk for exacerbations, changes on magnetic resonance imaging, and disability as measured by the Expanded Disability Status Scale. Currently, there are 8 therapies approved to treat multiple sclerosis: beta-interferons (Avonex, Betaseron, Extavia, and Rebif), fingolimod (Gilenya), glatiramer acetate (Copaxone), mitoxantrone (Novantrone), and natalizumab (Tysabri). These agents will be reviewed including the pivotal trial data, mechanisms of action, and side effects. The timing of beginning therapy and selection of these agents must be individualized for each patient depending upon patient preference, tolerability, clinical and magnetic resonance imaging disease activity, and disease course. All of the current treatments are approved for relapsing disease. To date only the injectable agents, including interferons and glatiramer acetate, have been shown to be of benefit when started after an initial demyelinating event referred to as clinically isolated syndrome. Mitoxantrone was approved for progressive relapsing and secondary progressive multiple sclerosis, although its use is limited by potential risks such as cardiotoxicity and leukemia. Although these agents have made a significant impact on the treatment of multiple sclerosis, they are often only partially effective, so patients may continue to have disease activity. Multiple new agents are currently being tested in clinical trials and it is likely our treatment paradigms will change as more effective therapies become available.