What are the treatment options for multiple sclerosis (MS)?

Treatment Options for Multiple Sclerosis

For relapsing-remitting MS, initiate high-efficacy disease-modifying therapies (DMTs) early in the disease course rather than using a traditional escalation approach, as this strategy improves long-term outcomes and prevents irreversible disability accumulation. 1, 2

Disease-Modifying Therapies by MS Subtype

Relapsing-Remitting MS (RRMS)

High-Efficacy DMTs (First-Line Options):

• Monoclonal antibodies including ocrelizumab, ofatumumab, natalizumab, and alemtuzumab are the most effective options when initiated early in the disease course. 1, 2
• Cladribine is also classified as high-efficacy and should be considered in the same category as monoclonal antibodies. 1
• These agents reduce annualized relapse rates by 29-68% compared with placebo or active comparators. 3

Moderate-Efficacy DMTs:

• Interferon beta-1a (intramuscular and subcutaneous formulations) and interferon beta-1b are indicated for relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. 4
• Glatiramer acetate (subcutaneous) provides moderate efficacy but is associated with lower adherence due to injection requirements. 5
• Oral agents including fingolimod, teriflunomide, and dimethyl fumarate offer convenient administration but lower efficacy than high-efficacy DMTs. 5, 3

Active Secondary Progressive MS

• Natalizumab is FDA-approved as monotherapy for active secondary progressive disease in adults. 6
• High-efficacy DMTs used for RRMS are also indicated when there is documented inflammatory activity. 1

Primary Progressive MS

• Ocrelizumab is the only FDA-approved DMT specifically for primary progressive MS, though its efficacy is primarily limited to slowing disability progression. 2, 3

Treatment Strategy Algorithm

For Newly Diagnosed RRMS

Initiate high-efficacy DMT immediately if ANY of the following are present: 1, 2

• Frequent relapses (≥2 per year)
• Incomplete recovery from relapses
• High frequency of new MRI lesions
• Rapid onset of disability
• Age <45 years with disease duration <10 years
• High focal inflammation on MRI
• EDSS score <4.0

Do NOT use traditional stepped escalation starting with moderate-efficacy agents, as this approach leads to worse long-term outcomes. 1, 2, 7

For Treatment-Refractory Disease

Consider autologous haematopoietic stem cell transplantation (AHSCT) when: 1

• Patient has failed ≥1 high-efficacy DMT after a meaningful treatment period
• Age <45 years
• Disease duration <10 years
• EDSS score <4.0
• Documented high focal inflammation on MRI
• No major cognitive impairment
• Excellent performance status
• No active infections or multiple medical comorbidities

AHSCT achieves 87% progression-free survival at 10 years in selected patients with relapsing-remitting MS, superior to continued DMT escalation. 1

For Progressive MS with Inflammatory Activity

AHSCT should only be considered for: 1

• Young individuals (<45 years)
• Short disease duration
• Well-documented clinical AND radiological evidence of inflammatory disease activity within the past 12 months
• Early progressive disease (not advanced)

Do NOT offer AHSCT for: 1

• Progressive MS without detectable inflammatory lesion activity
• Age >55 years
• Disease duration >20 years
• EDSS score >6.0
• Absence of focal inflammation
• Long-standing, advanced forms with severe disability

Critical Safety Considerations

Natalizumab-Specific Monitoring

• Progressive multifocal leukoencephalopathy (PML) risk increases with anti-JCV antibody positivity, duration of therapy, and prior immunosuppressant use. 6
• High-risk patients require brain MRI every 3-4 months to monitor for PML. 8, 6
• Natalizumab must be used as monotherapy only—never combine with other immunosuppressants. 6

Hepatitis B Screening

• All patients must be screened for hepatitis B core antibodies and surface antigens prior to initiating high-efficacy DMTs. 8
• If hepatitis B core antibody is positive: administer prophylaxis or monitor HBV DNA with pre-emptive antiviral treatment. 8
• If surface antigen is positive: administer antiviral prophylaxis under specialist control throughout immunosuppressive therapy. 8

AHSCT-Specific Risks

• Transplant-related mortality ranges from 0-2.8%, with higher rates in patients with advanced progressive disease. 1
• Requires multidisciplinary expertise across neurology, haematology, neuroradiology, physiotherapy, and laboratory medicine. 1

Monitoring Protocol

MRI Surveillance

• Every 3-4 months for highly active disease or recent treatment change. 8
• Every 6 months in the first year of treatment. 8
• Annually if disease remains stable. 2, 8

Clinical Monitoring

• Assess EDSS score at each visit to track disability progression. 9
• Evaluate for incomplete recovery after relapses as a trigger for DMT adjustment. 2

Common Pitfalls to Avoid

• Pseudoatrophy effect: Excessive brain volume decrease within the first 6-12 months of treatment due to resolution of inflammation should not be mistaken for disease progression. 2, 8
• Inappropriate washout periods: Inadequate transitions between DMTs can lead to complications from carryover effects or disease reactivation. 2, 8
• Delayed escalation: Waiting too long to escalate to high-efficacy therapy or AHSCT in aggressive disease allows irreversible disability accumulation. 1, 2
• Insurance misapplication: Ensure insurance companies apply MS treatment criteria, not criteria for unrelated conditions like Alzheimer's disease. 8