What is the treatment for multiple sclerosis (MS)?

Treatment of Multiple Sclerosis

Disease-modifying therapies (DMTs) are the cornerstone of multiple sclerosis treatment, with high-efficacy DMTs recommended as early intervention for patients with highly active disease to reduce inflammation, prevent relapses, and slow disability progression. 1, 2

Classification and Initial Assessment

• Multiple sclerosis is classified into relapsing-remitting (RRMS), secondary progressive (SPMS), and primary progressive (PPMS) forms, with treatment approaches varying by subtype 1
• Complete baseline MRI with contrast-enhanced T1 and T2/FLAIR sequences is essential to establish disease burden and monitor treatment response 1
• EDSS (Expanded Disability Status Scale) assessment helps determine treatment eligibility and monitor disease progression 1

First-Line Treatment Options

For Relapsing Forms of MS:

• FDA-approved injectable therapies:

  • Interferon beta-1a (Avonex) for relapsing forms including clinically isolated syndrome, relapsing-remitting, and active secondary progressive disease 3
  • Glatiramer acetate for relapsing forms of MS 2

• Oral therapies:

  • Dimethyl fumarate reduces brain atrophy compared to placebo 2
  • Fingolimod reduces brain atrophy compared to placebo 2
  • Teriflunomide decreases risk of conversion to MS in patients with clinically isolated syndrome 4

• Monoclonal antibodies:

  • Natalizumab for relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease 5
  • Ocrelizumab for both relapsing MS and primary progressive MS 2
  • Alemtuzumab more effective than interferon beta-1a in reducing annualized relapse rates in patients who experienced relapse on prior therapy 4

Treatment Strategy

• Current evidence supports early escalation and induction strategies rather than stepped care approaches 6, 1
• High-efficacy DMTs (alemtuzumab, natalizumab, ocrelizumab, ofatumumab) are more effective when initiated early in the disease course 6, 1
• For patients with markers of aggressive disease (frequent relapses, incomplete recovery, high lesion load on MRI, rapid disability onset), consider high-efficacy DMTs from the beginning 1

For Progressive Forms of MS:

• Ocrelizumab is approved for primary progressive MS 2, 7
• Autologous hematopoietic stem cell transplantation (AHSCT) is only indicated for secondary progressive or primary progressive MS with early, inflammatory active disease 6

Advanced Treatment Options

• For highly active MS not responding to high-efficacy DMTs, AHSCT can be considered as an appropriate escalation therapy 6
• AHSCT is most beneficial in patients:
  • Under 45 years of age 6
  • Disease duration less than 10 years 6
  • High focal inflammation 6
  • EDSS score less than 4.0 6

Monitoring Treatment Response

• Annual MRI brain scans are recommended for most patients 1
• More frequent monitoring (every 3-4 months) is needed for patients at high risk of serious adverse events, particularly those on natalizumab with risk factors for PML 1, 5
• Treatment failure is defined by continued relapses, new MRI lesions, or disability progression despite therapy 1

Safety Considerations

• Natalizumab increases risk of progressive multifocal leukoencephalopathy (PML), requiring careful monitoring and risk stratification based on JC virus antibody status, treatment duration, and prior immunosuppressant use 5
• Vaccines should be administered 4-6 weeks before starting immunosuppressive therapies or 4-6 months after the last treatment course 2
• For patients on interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, or S1P modulators, vaccination can occur at any time during treatment 2

Treatment Adjustments

• Early referral for AHSCT consideration is recommended for patients with highly active, treatment-refractory MS 6
• AHSCT is not recommended for patients over 55 years, those with disease duration >20 years, or those without focal inflammation 6, 1
• For patients over 55 years with stable disease, consider discontinuation of treatment as benefits may be outweighed by infection risks and other adverse effects 1

Common Pitfalls to Avoid

• Pseudoatrophy effect can cause excessive decrease in brain volume within 6-12 months of treatment due to resolution of inflammation, which should not be mistaken for disease progression 2
• Appropriate washout periods between different DMTs are essential to avoid complications from carryover effects 2
• Delaying treatment initiation can lead to irreversible neurological damage and poorer long-term outcomes 8