Advances in the management of relapsing-remitting multiple sclerosis: role of oral dimethyl fumarate (BG-12).

Abstract

Multiple sclerosis is a complex and chronic inflammatory disease of the central nervous system which affects an estimated 2.3 million individuals worldwide. Genetic research has uncovered over 100 immune-related genes associated with the disease and has provided a multitude of potential therapeutic targets. To date, 13 US Food and Drug Administration-approved disease-modifying therapies designed to influence the aberrant immune system are available for the indication of relapsing forms of the disease. BG-12 is a novel oral multiple sclerosis therapeutic with a unique putative mechanism of action that activates the Nrf2 anti-oxidant pathway. Despite the enthusiasm for multiple therapeutic options, including oral options, the practitioner is faced with the difficult task of providing guidance for patients regarding optimal sequencing of therapeutics without sensitive clinical biomarkers to match a particular therapy's putative mechanism of action to the patient's specific pathophysiology. Moreover, while BG-12 has a preferred route of administration, there is limited safety data with which to guide counseling in the clinic. Dimethyl fumarate (DMF or BG-12) is one of three available oral therapies which will be discussed in this review in terms of its pharmacokinetic profile, putative mechanism of action, clinical effectiveness, safety, tolerance, and patient-reported experience. BG-12's potential as a first-line therapy and as a sequencing therapeutic to aid in transition off natalizumab will be discussed.