Pharmacology and clinical efficacy of dimethyl fumarate (BG-12) for treatment of relapsing–remitting multiple sclerosis

Figures & data

Table 1 Summary of oral drugs for the treatment of relapsing-remitting multiple sclerosis

Therapy	Pivotal trials	Principal proposed mechanism of action	Administration	Common adverse events	Serious adverse events
Fingolimod	TRANSFORMS^Citation23 FREEDOMS^Citation22	Decreased expression of S1p1 on lymphocytes, resulting in sequestration of lymphocytes in lymphoid tissue.	0.5 mg oral tablet taken daily	Nasopharyngitis; headache; fatigue; lymphopenia; nausea; increased liver enzymes; back pain; diarrhea.	Disseminated varicella zoster; herpes simplex encephalitis; bradycardia; cardiac arrhythmias; bronchoconstriction; macular edema; skin neoplasms.
Teriflunomide	TEMSO^Citation55 TENERE^Citation56	Inhibition of pyrimidine biosynthesis in rapidly dividing cells.	14 mg oral tablet taken daily	Nasopharyngitis; gastrointestinal disturbance; back pain; elevated alanine aminotransferase; headache; fatigue; limb pain; urinary tract infection.	Hepatotoxicity; neutropenia; rhabdomyolysis; trigeminal neuralgia; neoplasm (solid tumors).
Dimethyl fumarate (BG-12)	DEFINE^Citation45 CONFIRM^Citation46	Decreases proinflammatory cytokines; decreases entrance of lymphocytes into CNS by decreased expression of adhesion molecules.	240 mg oral tablet taken either twice or thrice daily	Episodic flushing; gastrointestinal disturbance; headache; nasopharyngitis; fatigue.	Serious infection; gastroenteritis; neoplasm (solid tumor); gastritis.
Laquinimod*	ALLEGRO^Citation57 BRAVO^Citation58	Unknown in EAE; decreases entrance of lymphocytes into CNS; axon protection; decreases proinflammatory cytokines; increases levels of brain neurotrophic growth factor.	0.6 mg oral tablet taken daily	Chest pain; arthralgia; viral infection.	Hepatotoxicity; abnormal menstrual bleeding; exacerbation of preexisting glaucoma.

* Note: Laquinimod has not yet been approved for the treatment of MS.

Abbreviations: CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; MS, multiple sclerosis

Figure 1 Chemical structure of dimethyl fumarate (BG-12).

Figure 2 Effects of fumaric acid esters on immune and accessory cells.

Abbreviations: Th, T-helper; TNF, tumor necrosis factor; ICAM-1, intercellular adhesion molecule 1; VCAM-1, vascular cell adhesion molecule-1.

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