Multiple Sclerosis Agents

Review
In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
.

Excerpt

Multiple sclerosis is a chronic demyelinating disorder of the central nervous system of unknown etiology. It is most likely caused by a gradual, intermittent autoimmune destruction of myelin. The disorder is characterized by a relapsing-remitting course, but in a small proportion of patients, it is unremittingly progressive even from the onset. The disease typically presents between the ages of 20 and 40 years and is more common in women than men. Rates of multiple sclerosis vary geographically, being highest in Northern parts of Europe and the United States and in Canada. Multiple sclerosis affects an estimated 400,000 persons in the United States and is the most common cause of neurologic disability in young adulthood.

Therapies of multiple sclerosis can be divided into disease modifying agents and symptomatic therapies. The disease modifying agents are largely immunomodulatory drugs including interferon beta-1a (Avonex, 1994 and Rebif, 2003), interferon beta-1b (Betaseron and Extavia, 1993), peginterferon beta-1a (Plegridy, 2014), glatiramer acetate (Copaxone and Glatopa 1996), alemtuzumab (Lemtrada, 2001), natalizumab (Tysabri, 2004), mitoxantrone (generic, 2006), fingolimod (Gilenya, 2010), teriflunomide (Aubagio, 2012), three fumarates (dimethyl fumarate: Tecfidera, 2013; diroximel fumarate: Vumerity, 2019; and monomethyl fumarate: Bafiertam, 2020), ocrelizumab (Ocrevus, 2017), daclizumab (Zinbryta, 2017; withdrawn 2018), cladribine (Mavenclad, 2018), siponimod (Mayzent, 2019), ozanimod (Zeposia, 2020) and Ponesimod (Ponvory, 2021). Disease modifying agents that are used in resistant cases of multiple sclerosis some of which are not specifically approved for this use (off-label use) include methotrexate, cyclophosphamide, and intravenous immunoglobulins. The disease modifying agents are more effective in relapsing-remitting forms of disease than in the more severe and intractable progressive forms. Symptomatic therapies developed for multiple sclerosis include dalfampridine (4-aminopyrine; Ampyra, 2010), a potassium channel blocker that improves mobility and walking speed in patients with relapsing-remitting forms of multiple sclerosis.

While transient, asymptomatic and mild-to-moderate serum aminotransferase elevations occur not uncommonly with most of the drugs used to treat multiple sclerosis, clinically apparent hepatotoxicity is rare. Nevertheless, several convincing instances of acute liver injury have been reported for the various forms of interferon beta, glatiramer acetate, dimethyl fumarate, alemtuzumab, daclizumab, and fingolimod. Importantly, clinically apparent liver injury was usually first attributed to these agents several years after their introduction, and initially they were not believed to be hepatotoxic. Thus, many of the more recently introduced agents (fingolimod, siponimod, ozanimod, ponesimod, teriflunomide, cladribine, and the fumarates) have not had wide enough general use to state that they do not cause clinically apparent liver injury, and all have been associated occasionally with marked but transient increases in serum aminotransferase levels.

Publication types

  • Review