Established and novel disease‐modifying treatments in multiple sclerosis

<jats:title>Abstract</jats:title><jats:p>Multiple sclerosis (<jats:styled-content style="fixed-case">MS</jats:styled-content>) is a presumed autoimmune disorder of the central nervous system, resulting in inflammatory demyelination and axonal and neuronal injury. New diagnostic criteria that incorporate magnetic resonance imaging have resulted in earlier and more accurate diagnosis of <jats:styled-content style="fixed-case">MS</jats:styled-content>. Several immunomodulatory and immunosuppressive therapeutic agents are available for relapsing forms of <jats:styled-content style="fixed-case">MS</jats:styled-content>, which allow individualized treatment based upon the benefits and risks. Disease‐modifying therapies introduced in the 1990s, the beta‐interferons and glatiramer acetate, have an established track record of efficacy and safety, although they require administration via injection. More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha‐4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example <jats:styled-content style="fixed-case">CD</jats:styled-content>52 (alemtuzumab) or <jats:styled-content style="fixed-case">CD</jats:styled-content>20 (ocrelizumab and ofatumumab). These agents can be highly efficacious, but sometimes have serious potential complications (natalizumab is associated with progressive multifocal leukoencephalopathy; alemtuzumab is associated with the development of new autoimmune disorders). Three new oral therapies (fingolimod, teriflunomide and dimethyl fumarate, approved for <jats:styled-content style="fixed-case">MS</jats:styled-content> treatment from 2010 onwards) provide efficacy, tolerability and convenience; however, as yet, there are no long‐term postmarketing efficacy and safety data in a general <jats:styled-content style="fixed-case">MS</jats:styled-content> population. Because of this lack of long‐term data, in some cases, therapy is currently initiated with the older, safer injectable medications, but patients are monitored closely with the plan to switch therapies if there is any indication of a suboptimal response or intolerance or lack of adherence to the initial therapy. For patients with <jats:styled-content style="fixed-case">MS</jats:styled-content> who present with highly inflammatory and potentially aggressive disease, the benefit‐to‐risk ratio may support initiating therapy using a drug with greater potential efficacy despite greater risks (e.g. fingolimod or natalizumab if <jats:styled-content style="fixed-case">JC</jats:styled-content> virus antibody‐negative). The aim of this review is to discuss the clinical benefits, mechanisms of action, safety profiles and monitoring strategies of current <jats:styled-content style="fixed-case">MS</jats:styled-content> disease‐modifying therapies in clinical practice and of those expected to enter the market in the near future.</jats:p>