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Dimethyl fumarate for treatment of multiple sclerosis: mechanism of action, effectiveness, and side effects.

Abstract
Dimethyl fumarate is an orally available treatment option for relapsing-remitting multiple sclerosis (MS) in a new formulation with improved gastroenteric coating. The mode of action comprises immunomodulatory effects and an activation of nuclear (erythroid-derived 2) related factor mediated antioxidative response pathways leading to additional cytoprotective effects. In two pivotal phase III trials, dimethyl fumarate, 240 mg twice daily, reduced relapse rates by about 50 % as compared with placebo. In the DEFINE trial, progression of disability was also significantly reduced. Both trials demonstrated a significant reduction of gadolinium-enhanced lesions as well as T2 lesions on cranial MRI. The studies revealed a beneficial safety profile of dimethyl fumarate. The most prevalent side effects were transient flushing and gastrointestinal tract irritation. Dimethyl fumarate has recently been approved in the USA for the treatment of relapsing-remitting MS. The compound is a welcome addition to the immunomodulatory treatment armamentarium for MS patients and physicians alike.
AuthorsRalf A Linker, Ralf Gold
JournalCurrent neurology and neuroscience reports (Curr Neurol Neurosci Rep) Vol. 13 Issue 11 Pg. 394 (Nov 2013) ISSN: 1534-6293 [Electronic] United States
PMID24061646 (Publication Type: Journal Article, Review)
Chemical References
  • Fumarates
  • Immunosuppressive Agents
  • Dimethyl Fumarate
Topics
  • Animals
  • Clinical Trials as Topic (methods)
  • Dimethyl Fumarate
  • Fumarates (adverse effects, pharmacokinetics, therapeutic use)
  • Gastrointestinal Diseases (chemically induced, immunology, metabolism)
  • Humans
  • Immunosuppressive Agents (adverse effects, pharmacokinetics, therapeutic use)
  • Multiple Sclerosis (drug therapy, immunology, metabolism)
  • Treatment Outcome

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