What is the recommended treatment regimen for relapsing forms of Multiple Sclerosis (MS)?

From the Guidelines

Dimethyl fumarate (Tecfidera) is a recommended oral disease-modifying therapy for relapsing forms of Multiple Sclerosis, taken twice daily, as part of a comprehensive treatment plan that includes regular monitoring and symptomatic treatments. The treatment regimen for relapsing forms of MS typically involves starting disease-modifying therapies (DMTs) as early as possible after diagnosis. First-line options include injectable medications like interferon beta or glatiramer acetate, or oral options like fingolimod, dimethyl fumarate, or teriflunomide 1. For more aggressive disease, monoclonal antibodies like natalizumab or ocrelizumab may be used. Treatment selection depends on disease severity, patient preferences, side effect profiles, and comorbidities.

Some key points to consider when using dimethyl fumarate include:

• Starting dose: 120 mg twice daily for the first 7 days, then increased to 240 mg twice daily
• Monitoring: regular MRI scans and neurological examinations every 6-12 months to assess efficacy
• Side effects: gastrointestinal symptoms, flushing, and lymphopenia are common, but usually decrease over time
• Contraindications: severe renal impairment, moderate to severe hepatic impairment, and known hypersensitivity to dimethyl fumarate or any component of the formulation. Recent guidelines from ectrims and the ebmt also discuss the use of autologous haematopoietic stem cell transplantation (AHSCT) for treatment of MS, but this is typically reserved for refractory cases or aggressive forms of the disease 1.

In terms of AHSCT, some key recommendations include:

• Intermediate-intensity conditioning protocols, such as BEAM–ATG or cyclophosphamide–ATG, are recommended to achieve the best balance of efficacy and risk in most settings
• Low-intensity regimens are not recommended outside clinical trials owing to poor evidence of efficacy
• High-intensity, myeloablative conditioning protocols are not recommended outside clinical trials owing to a higher risk of toxicity. It's essential to weigh the benefits and risks of each treatment option and consider individual patient factors, such as disease severity and comorbidities, when making treatment decisions.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Starting dose: 120 mg twice a day, orally, for 7 days (2. 1) Maintenance dose after 7 days: 240 mg twice a day, orally (2.1)

The recommended treatment regimen for relapsing forms of Multiple Sclerosis (MS) with dimethyl fumarate is a starting dose of 120 mg twice a day for 7 days, followed by a maintenance dose of 240 mg twice a day. It is essential to swallow the delayed-release capsules whole and intact, and they can be taken with or without food 2.

• Key points:
  • Starting dose: 120 mg twice a day for 7 days
  • Maintenance dose: 240 mg twice a day
  • Administration: orally, with or without food
  • Capsules: swallow whole and intact, do not crush, chew, or sprinkle contents on food

From the Research

Dimethyl Fumarate for Relapsing Forms of Multiple Sclerosis (MS)

• Dimethyl fumarate (Tecfidera®) is approved for the treatment of relapsing forms of multiple sclerosis (MS) 3.
• It has been shown to be an effective treatment in reducing clinical relapse and MRI measures of disease activity, and improving some aspects of health-related quality of life (HR-QoL) 3, 4.

Treatment Regimen

• The recommended treatment regimen for dimethyl fumarate is twice-daily oral administration 3.
• A dose of 240 mg orally three times daily or twice daily has been shown to reduce the number of patients with a relapse and the annualised relapse rate over two years of treatment in comparison with placebo 4.

Efficacy and Safety

• Dimethyl fumarate has been shown to have an acceptable tolerability profile, with the most common adverse events being flushing and gastrointestinal events, which are typically mild or moderate in severity 3, 4.
• Uncommon adverse events include lymphopenia and leukopenia, which are more likely to occur with dimethyl fumarate than with placebo 4.
• Management strategies, such as administering dimethyl fumarate with food, using a slower-dose titration schedule, and applying temporary dose reductions, can help to address tolerability issues 5.

Patient-Reported Outcomes

• Patient-reported outcomes (PROs) have shown that dimethyl fumarate is associated with improved health-related quality of life, reduced work productivity impairment, and less impairment in fatigue and depression scales 6.
• PROs can provide a more patient-centered approach to MS care and help to better address the aspects of patient care that are not captured by objective assessment tools 6.

Mechanisms of Action

• Dimethyl fumarate has been proposed to have anti-inflammatory, neuroprotective, and myelin-protective mechanism actions, making it a possible candidate for MS treatment 7.
• Its exact mechanisms of action are not fully understood, but it is thought to involve the modulation of immune responses and the protection of the central nervous system 7.