Current and emerging multiple sclerosis therapeutics.

Greenberg, Benjamin M; Khatri, Bhupendra O; Kramer, John F

For a disease whose cause remains elusive, there has been a paradoxical growth in multiple sclerosis (MS) therapeutics. During the past 17 years, six therapeutic drugs for MS were brought to market. All of these disease-modifying therapies (DMTs) have shown a beneficial effect in reducing the number of exacerbations in double-blind placebo-controlled trials, and three drugs (subcutaneous [SC]/IM interferon beta-1a, natalizumab) have been shown to reduce relapses, decrease MRI activity, and reduce the risk of sustained disability after 2 years of treatment. No controlled studies exist to show long-term benefit with any of the current DMTs. Immunosuppressive drug (ISD) therapies continue to play a role in the management of patients who fail to respond to immunomodulatory agents. These agents, however, have shown mixed data in terms of efficacy and put patients at higher risk for the development of secondary cancers. Plasma exchange for severe relapses not responsive to corticosteroid therapy has regained interest in the past few years. Furthermore, six new agents that will dramatically impact our ability to prevent disability in patients with MS are in late-stage or have completed phase 3 clinical development. Determining the risk-benefit calculations that we will need to employ toward these new drugs and the algorithms for switching therapies will be critical issues in the next 5 years. This article highlights the clinical efficacy of the current DMTs/ISDs and discusses the current treatment options for clinically isolated syndrome, relapsing-remitting MS (RRMS), and exacerbations of RRMS. It also addresses the management of a suboptimal response to the DMTs; discusses the challenge of primary progressive MS; and presents an overview of emerging therapeutic options.