Dimethyl Fumarate for Treatment of Multiple Sclerosis: Mechanism of Action, Effectiveness, and Side Effects
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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.
KeywordsMultiple sclerosis Neuroinflammation Oral Immunotherapy Neuroprotection Clinical trial Dimethyl fumarate Effectiveness Side effects
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Conflict of Interest
Ralf A. Linker has been a consultant for Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis Pharma, and TEVA Pharma, has received grant support from Biogen Idec, Merck Serono, and Novartis Pharma, has received honoraria from Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis, and TEVA Pharma, has patents (planned, pending, or issued) for Biogen Idec, has received payment for development of educational presentations including service on speakers bureaus from Novartis Pharma, and has received travel/accommodation expenses covered or reimbursed by Bayer, Biogen Idec, Genzyme, Merck Serono, Novartis Pharma, and TEVA Pharma.
Ralf Gold has received grant support from Biogen Idec for investor-sponsored experimental trials, has received a consulting fee or honorarium for the board or speaker honoraria for Biogen Idec, and has received support for travel to meetings for study or otherwise for steering committee meetings for Biogen Idec.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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