Update on disease-modifying therapies for multiple sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). It predominantly affects young women and is one of the most common causes of disability in young adults. MS is characterized by formation of white matter lesions in the CNS as a result of inflammation, demyelination, and axonal loss. Treatment has been a focus of neurological research for over 60 years. A number of disease-modifying therapies (DMTs) have become available making MS a treatable disease. These compounds target the inflammatory response in MS. They work by decreasing the chances of relapse, decreasing the chances of new lesion formation seen on MRI of the CNS and slowing the accumulation of disability. The first drugs for MS to be available were interferon-β and glatiramer acetate. These work by modulating the inflammatory response via different mechanisms that are briefly discussed. Newer agents have since become available and have significantly changed the dynamics of MS treatment. These include fingolimod, dimethyl fumarate and teriflunomide, which are oral agents. Other second-line and third-line Food and Drug Administration (FDA) approved medications include natalizumab and alemtuzumab. Natalizumab is considered one of the most potent treatments for relapse prevention. However, the high risk of progressive multifocal leukoencephalopathy (PML), which is caused by JC virus infection in the brain, tempers the more widespread use of this agent; nevertheless, JC virus antibody tests have helped to stratify the risk of PML. Alemtuzumab, which also has a considerable side effect profile, is likewise highly efficacious. Ocrelizumab, a monoclonal antibody to CD20 on B cells, is a highly effective agent for MS that is likely to be approved soon by the FDA. MS is a major contributor to healthcare costs and it is critical that healthcare providers be aware of the availability and benefits of DMTs. It is imperative that prompt and adequate treatment be established on diagnosis. Changes in therapy should be considered when there is evidence of disease activity as well as accumulation of disability or safety or tolerability concerns.