What are the simplified guidelines for pharmacotherapy in Multiple Sclerosis (MS)?

From the Guidelines

Pharmacotherapy for multiple sclerosis (MS) should prioritize disease-modifying therapies (DMTs) that reduce relapses, slow disease progression, and manage symptoms, with treatment selection guided by disease activity, patient preferences, and potential side effects. When considering DMTs, first-line treatments for relapsing-remitting MS include injectable medications like interferon beta and glatiramer acetate, as well as oral options such as fingolimod, dimethyl fumarate, and teriflunomide 1. For more aggressive disease or inadequate response to first-line treatments, higher-efficacy options like natalizumab, ocrelizumab, and alemtuzumab may be considered, with specific monitoring requirements for side effects like progressive multifocal leukoencephalopathy (PML) 1.

Key Considerations for DMT Selection

• Disease activity and progression
• Patient preferences regarding administration route
• Potential side effects and monitoring requirements
• Pregnancy plans and JC virus antibody status
• Regular monitoring for side effects and adjustment of treatment as needed

Monitoring and Safety Protocols

• Baseline testing including blood work, MRI, and sometimes JC virus antibody status
• Regular MRI screening for patients at high risk of PML, such as those treated with natalizumab 1
• Enhanced pharmacovigilance, including brain MRI every 3-4 months for up to 12 months, for patients switching from natalizumab to other therapeutics 1

Symptom Management

• Additional medications for fatigue, spasticity, pain, and bladder dysfunction
• Mechanisms of action including modulating immune responses, preventing immune cell migration into the central nervous system, or depleting specific immune cell populations to reduce inflammatory attacks on myelin 1

From the FDA Drug Label

Teriflunomide is a pyrimidine synthesis inhibitor 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. Fingolimod 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 patients 10 years of age and older. AVONEX is 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.

The guidelines for pharmacotherapy for MS include:

• Teriflunomide: 7 mg or 14 mg orally once daily, with or without food 2
• Fingolimod: dosing information not provided in the label excerpt 3
• Interferon beta-1a: 30 micrograms once a week, with titration to reduce flu-like symptoms 4 Key considerations:
• Monitor liver function and blood cell counts
• Consider discontinuation if depression, hepatic injury, or other adverse reactions occur
• Use effective contraception in females of reproductive potential during treatment with teriflunomide 2

From the Research

Pharmacotherapy for MS

• The mainstays of treatment in relapsing-remitting multiple sclerosis include interferon beta and glatiramer acetate 5.
• These drugs have been used for two decades and have undergone significant advances in understanding their immune function and dysfunction, as well as clinical trial design 5.
• The clinical use of interferon beta and glatiramer acetate includes evaluating tolerability, side effects, and efficacy measures 5.

Treatment Recommendations

• The initial phases of relapsing-remitting multiple sclerosis are characterized by a mainly inflammatory pathology, which gives way to a largely neurodegenerative process as the disease evolves 6.
• Disease-modifying therapies aim to control inflammation, and the window of opportunity for use is early in the disease course 6.
• Approximately 30% of patients treated with first-line immunomodulators show a suboptimal response during the first 1-2 years and require a switch to an alternative therapy 6.
• Regular monitoring of disease and therapy in patients with MS is essential, including clinical evaluations and brain magnetic resonance imaging (MRI) every 6 months in the first year of treatment 6.

Disease-Modifying Therapies

• First-line disease-modifying therapies include interferon beta and glatiramer acetate 7.
• Patients with a poor prognosis may require a timely switch to a second-line agent 6.
• Lifestyle modifications, such as smoking cessation, vitamin D supplementation, and a healthy diet, may improve long-term outcomes 7.
• Treatment decisions should be made in collaboration with patients using the shared decision-making approach 7.

Treatment Outcomes

• Glatiramer acetate has been shown to be effective in treatment-naïve and prior interferon-beta-1b-treated multiple sclerosis patients 8.
• Subcutaneous interferon β-1a and dimethyl fumarate have been compared in a real-world study, with no difference observed in time to overall non-persistence between the two treatment groups 9.
• However, dimethyl fumarate-treated patients had a higher risk of experiencing a discontinuation and an adverse event compared to subcutaneous interferon β-1a-treated patients 9.