What is the recommended treatment for multiple sclerosis (MS)?

Treatment Recommendations for Multiple Sclerosis

For patients with relapsing forms of multiple sclerosis (MS), early initiation of disease-modifying therapy (DMT) is strongly recommended, with high-efficacy DMTs being preferred for those with highly active disease, while autologous hematopoietic stem cell transplantation (AHSCT) should be considered for patients with treatment-refractory MS. 1, 2

Disease-Modifying Therapies for Relapsing Forms of MS

First-Line Treatment Options

• FDA-approved DMTs for relapsing forms of MS (including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease):
  • Interferon beta-1a (IM and SQ formulations) 3, 4
  • Dimethyl fumarate 5
  • Glatiramer acetate
  • Teriflunomide

High-Efficacy DMTs

• Monoclonal antibodies:
  • Natalizumab
  • Ocrelizumab
  • Ofatumumab
  • Alemtuzumab
• Sphingosine 1-phosphate receptor modulators (fingolimod)
• Cladribine

Treatment Algorithm Based on Disease Activity

For Newly Diagnosed MS:

1. Mild-to-Moderate Disease Activity:

   • Start with first-line agents (interferons, glatiramer acetate, teriflunomide, dimethyl fumarate)
   • Monitor for breakthrough disease activity

2. Highly Active Disease at Onset:

   • Initiate high-efficacy DMTs (natalizumab, ocrelizumab, ofatumumab)
   • Consider JCV antibody status before starting natalizumab to assess PML risk 2

3. Treatment Monitoring:

   • Regular brain MRI assessment (yearly)
   • Clinical evaluation for new neurological symptoms
   • JCV antibody testing every 6 months for patients on natalizumab 2

For Treatment-Refractory MS:

1. After Failure of First-Line DMTs:

   • Escalate to high-efficacy DMTs

2. After Failure of High-Efficacy DMTs:

   • Consider AHSCT for patients with:
     • Age <45 years
     • Disease duration <10 years
     • EDSS score <4.0
     • Evidence of inflammatory activity 1

3. For Rapidly Evolving Severe MS:

   • Consider AHSCT as part of a clinical trial or observational study 1

Treatment for Progressive Forms of MS

For Secondary Progressive MS with Active Disease:

• Ocrelizumab
• Siponimod
• Consider AHSCT only for those with:
  • Early disease
  • Short disease duration
  • Evidence of inflammatory activity 1

For Primary Progressive MS:

• Ocrelizumab is the only FDA-approved treatment 6
• AHSCT may be considered only for those with early, inflammatory active disease 1

Important Considerations and Caveats

Timing of Treatment:

• Early initiation of DMTs is crucial to prevent irreversible neurological damage 7, 8
• Long-term studies show that early treatment with high-efficacy DMTs like natalizumab provides better outcomes compared to traditional first-line therapies 8

Treatment Selection Factors:

• Disease activity (relapse frequency, MRI lesions)
• Risk tolerance
• Comorbidities
• Pregnancy planning
• Route of administration preferences

Treatment Switching:

• Consider washout periods when switching between DMTs to avoid complications from overlapping immune effects 2
• Monitor for breakthrough disease (new relapses or MRI activity)

AHSCT Considerations:

• Not recommended for:
  • Patients >55 years
  • Disease duration >20 years
  • EDSS score >6.0
  • Absence of inflammatory activity
  • Multiple medical comorbidities 1

Vaccination Recommendations:

• Complete hepatitis B vaccination series before starting potent MS therapy
• Administer vaccines 4-6 weeks before starting ocrelizumab or 4-6 months after ending treatment 2

Early diagnosis and prompt initiation of appropriate DMT are essential for optimizing long-term outcomes in MS. The treatment landscape continues to evolve with newer therapies offering improved efficacy, though careful consideration of benefit-risk profiles remains critical.