What is the role of Dimethylfumarate (Multiple Sclerosis treatment) in Multiple Sclerosis (MS)?

From the Guidelines

Dimethyl fumarate is a valuable treatment option for relapsing-remitting multiple sclerosis (RRMS), with a standard dosing regimen and potential side effects that can be managed with proper monitoring and patient education. The medication works by activating the Nrf2 pathway, reducing oxidative stress and inflammation, and has been shown to decrease the frequency of MS relapses and slow disease progression 1.

Key Considerations

• The standard dosing regimen for dimethyl fumarate begins with 120 mg twice daily for 7 days, then increases to the maintenance dose of 240 mg twice daily.
• Common side effects include flushing and gastrointestinal symptoms like nausea, diarrhea, and abdominal pain, which typically improve over time.
• Taking the medication with food can help minimize these effects.
• Before starting treatment, patients should have baseline blood tests including complete blood count, liver function tests, and a tuberculosis screening.
• Regular monitoring of lymphocyte counts is necessary as dimethyl fumarate can cause lymphopenia.

Efficacy and Safety

• Dimethyl fumarate has shown efficacy in reducing relapse rates by approximately 50% and decreasing new MRI lesions, making it a valuable option in the treatment arsenal for multiple sclerosis 1.
• The medication is contraindicated in pregnancy, and women of childbearing potential should use effective contraception.
• Patients should be aware that flushing reactions can be reduced by taking aspirin 30 minutes before the dose.
• In the context of COVID-19 vaccination, patients being treated with dimethyl fumarate can be vaccinated at any time during their treatment, despite the likely vaccine response attenuation 1.

Monitoring and Follow-up

• Brain MRI screening is recommended every 3-4 months for patients at high risk of PML (JCV seropositive, treatment duration ≥18 months) who are treated with natalizumab, and once a year for patients at low risk of PML (JCV seronegative) 1.
• Enhanced pharmacovigilance, including brain MRI every 3-4 months for up to 12 months, is required in patients who switch from natalizumab to other therapeutics, including dimethyl fumarate 1.

From the FDA Drug Label

Dimethyl fumarate delayed-release capsules are indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Dimethyl fumarate delayed-release capsules are a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

The role of Dimethylfumarate in Multiple Sclerosis (MS) is to treat relapsing forms of the disease, including:

• Clinically isolated syndrome
• Relapsing-remitting disease
• Active secondary progressive disease in adults 2, 2, 2.

From the Research

Role of Dimethylfumarate in Multiple Sclerosis

• Dimethyl fumarate is an effective treatment for relapsing-remitting multiple sclerosis (RRMS), with benefits maintained over the longer term 3.
• It reduces clinical relapse and MRI measures of disease activity, and improves some aspects of health-related quality of life (HR-QoL) 3, 4.
• The treatment dosage of dimethyl fumarate is typically 240 mg orally twice daily, which has been shown to reduce the number of patients with a relapse and disability worsening over two years of treatment compared to placebo 5.
• Dimethyl fumarate has an acceptable tolerability profile, with the most common adverse events being flushing and gastrointestinal events, which are generally mild or moderate in severity 3, 5, 4.

Efficacy and Safety

• Studies have shown that dimethyl fumarate reduces the annualised relapse rate and the number of patients with disability worsening over two years of treatment compared to placebo 5.
• The treatment median follow-up time on-drug was 12 months, with 15.8% of patients developing lymphopenia grade 2 or higher 6.
• Baseline lymphocyte counts and older age were significant predictors of lymphopenia, while higher baseline eosinophil counts predicted flushing/gastrointestinal adverse effects 6.
• Higher baseline monocyte counts were predictive of breakthrough disease activity, and neutrophil and platelet to lymphocyte ratios were increased at month 3 6.

Patient Experience and Adherence

• Patient-reported outcomes (PROs) assessment revealed stabilization or boost in health-related quality of life and work productivity of patients treated with dimethyl fumarate compared to placebo 7.
• However, literature suggests that intolerance to side effects, especially gastrointestinal adverse effects and flushing, is one of the major causes of compromised therapeutic compliance 7.
• Several prevention and mitigation strategies, such as patient counseling, dose up-titration, pretreatment with aspirin, use of symptomatic therapy, and frequent blood monitoring, have demonstrated to be effective in tackling these adverse effects and promoting adherence to dimethyl fumarate 7.