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 thirdline Food and Drug Administration (FDA) approved medications include natalizumab and alemtuzumab.

A standardised frankincense extract reduces disease activity in relapsing-remitting multiple sclerosis (the SABA phase IIa trial)

“…It is now widely recommended that anti-inflammatory treatment be started early in the relapsing phase of the disease to prevent the development of chronic neuroinflammation and neurodegeneration 2. Several anti-inflammatory drugs have been licensed, but most of these act broadly on the immune system, and require close monitoring for risks and side effects 3. The long-term treatment of MS that is initiated early in the course of the disease therefore requires a—as yet unavailable—very well-tolerated, safe, oral immunomodulatory treatment, particularly for those patients with only mild clinical involvement and indications of a benign course.…”

The Rapidly Changing Landscape of Multiple Sclerosis Immunomodulatory Therapy: A Retrospective Chart Review in the United Arab Emirates

“…For example, fingolimod was shown to carry the risk of bradycardia and atrioventruicular conduction block as well as macular edema, leading to regulations requiring increased monitoring before use [5,16]. Another oral medication, teriflunomide, was found to be teratogenetic, limiting its use in pregnant and nursing women [17].…”

“…Another oral medication, teriflunomide, was found to be teratogenetic, limiting its use in pregnant and nursing women [17]. The excitement surrounding the development of natalizumab, the first humanized monoclonal antibody for the treatment of MS, was also tempered after the emergence of the rare but dangerous side effect of progressive multifocal leukoencephalopathy [5]. Additionally, the most recent antibody, alemtuzumab, was shown to be associated with significant secondary autoimmune conditions including thyroid disease and idiopathic thrombocytopenic purpura [18].…”

“…Natalizumab, the first monoclonal antibody approved for the treatment of MS, was developed in 2004 and is administered via monthly infusions. Most recently on the market is alemtuzumab, approved as a third line therapy in 2013 and ocrelizumab just approved by the FDA in March 2017 [5].…”

“…Therefore, there was significant excitement over the development of the first oral DMT, fingolimod, introduced in 2010. This was followed by two others, teriflunomide and dimethyl fumarate (DMF) [5]. These newer oral medications allow patients to avoid injection-related side effects and improve the ease of medication administration.…”