Class: Fumeric acids, Nrf2 activators

Name: Dimethyl fumarate (Tecfidera®); Diroximel fumarate (Vumerity®); Monomethyl fumarate (Bafiertam®)

Frequency: Twice daily, with differing dosages for each product. All are oral medications.

Mechanism of Action: Exact mechanism is unknown, but thought to work by inhibiting what is known as Nrf-2 Activation.

Effectiveness: Moderately effective: decreases relapses by 50%; decreases MRI activity by 50%; decreases brain atrophy by 30%.

Possible Side Effects: Up to 40% will experience some form of GI problem, including nausea, vomiting, abdominal pain or diarrhea, in the first several weeks, and similarly up to 40% may experience flushing for 10-30 minutes about 30 minutes after taking the DMT. These are taken with food, and slowly escalated over the first month to limit these effects. GI problems are likely less with Vumerity and possibly less with Bafiertam. There have been a handful of cases of PML***, especially in patients over 50 and with low white blood cells, lymphocytes.

Oral BG-12, also known as dimethyl fumarate I, is an oral treatment for people with relapsing-remitting multiple sclerosis (RRMS) that received FDA approval in 2013. The oral therapy was a new class in treatment for MS in that it appears to have dual anti-inflammatory and neuroprotective effects. Originally used to treat psoriasis, the drug received Fast Track designation from the U.S. Food and Drug Administration (FDA) in 2008 as a treatment for MS.

BG-12, an oral fumarate derivative, has been shown to activate the Nrf2 transcriptional pathway—the first compound to do so. This pathway is thought to defend against oxidative-stress induced neuronal death, protect the blood-brain barrier, and support maintenance of myelin integrity in the central nervous system—all key elements to treating MS.

Video recorded in 2015.

*** PML (Progressive Multifocal Leukoencephalopathy): PML is a rare but serious brain infection that is caused by the JC Virus (JCV). PML is seen in MS patients who are JC virus (JCV) positive and on disease modifying therapies known to increase the risk of PML. At least 50% of the general population has been exposed to JCV, but the infection is generally asymptomatic. But, in immunocompromised patients, including those taking certain MS DMTs, the JC Virus can infect the brain and result in PML. PML The first case of PML in MS was discovered in 2005 with the use of Tysabri.