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

Treatment Options for Multiple Sclerosis

For patients with multiple sclerosis, a stepped approach using disease-modifying therapies (DMTs) based on disease subtype and activity is recommended, with autologous hematopoietic stem cell transplantation (AHSCT) reserved for cases refractory to high-efficacy DMTs. 1, 2

Disease-Modifying Therapies by MS Subtype

Relapsing Forms of MS (RRMS, CIS, Active SPMS)

• First-line options:

  • Interferon beta-1b (Betaseron): Reduces relapse rates and delays disability progression 3
  • Glatiramer acetate (Glatopa): Effective for relapsing forms of MS 4
  • Note: These medications require frequent injections and may take up to 6 months to become fully effective 2

• High-efficacy options (for highly active disease or suboptimal response to first-line therapy):

  • Natalizumab (Tysabri): 300mg IV infusion every four weeks; reduces annual relapse rates by 68% compared to placebo 2, 5
    • CAUTION: Requires JCV antibody monitoring every 6 months due to PML risk 2, 5
    • Contraindicated in JCV-positive patients with prolonged treatment duration
  • Ocrelizumab: CD20-directed monoclonal antibody; highly effective for relapsing MS 2
  • Ofatumumab: Alternative high-efficacy option 2
  • Cladribine (Mavenclad): Effective for highly active relapsing MS 2

Primary Progressive MS

• Ocrelizumab: The only FDA-approved treatment for primary progressive MS 2

Secondary Progressive MS with Activity

• All DMTs approved for relapsing forms can be used 3, 4
• Evidence suggests AHSCT may slow disability progression compared to standard immunotherapy in active SPMS 1

Monitoring Disease Activity and Treatment Response

1. MRI monitoring:

   • Annual brain MRI for all MS patients 2
   • Enhanced monitoring (every 3-4 months) for:
     • JCV-positive patients on natalizumab (treatment ≥18 months)
     • Patients switching between DMTs 2

2. Treatment failure indicators:

   • New relapses
   • Increasing disability (EDSS score)
   • New T2 or gadolinium-enhancing lesions on MRI 2
   • Note: New T2 lesions within first 6 months of therapy may not indicate treatment failure 2

Autologous Hematopoietic Stem Cell Transplantation (AHSCT)

AHSCT should be considered for:

• Patients who have failed ≥1 high-efficacy DMT with poor prognostic factors
• Patients with increasing EDSS scores despite treatment
• Young (<45 years) individuals with early disease and evidence of inflammatory activity 1, 2

The MIST trial demonstrated AHSCT superiority over conventional DMTs with:

• 90% vs 25% progression-free survival at 5 years
• 85% vs 15% relapse-free survival at 5 years
• 78% vs 3% NEDA-3 at 5 years 1

Safety Considerations

1. Before starting treatment:

   • Complete hepatitis B vaccination
   • Administer appropriate vaccines 4-6 weeks before starting therapy 2
   • No concurrent use of live vaccines 2

2. During treatment:

   • Monitor for treatment-specific adverse effects:
     • Interferons: Flu-like symptoms, injection site reactions 6, 7
     • Natalizumab: PML risk (requires strict monitoring protocol) 5
     • AHSCT: Short-term risks during procedure, but potential for long-term remission 1

3. After discontinuing treatment:

   • Monitor for Immune Reconstitution Inflammatory Syndrome (IRIS) 2

Treatment Algorithm

1. New diagnosis:

   • Determine MS subtype (relapsing vs. progressive)
   • Assess disease activity (clinical relapses, MRI activity)
   • Consider age, comorbidities, and pregnancy plans

2. For relapsing forms with mild-moderate activity:

   • Start with first-line DMT (interferon beta-1b or glatiramer acetate)
   • Monitor with annual MRI and clinical assessment

3. For highly active disease or suboptimal response:

   • Switch to high-efficacy therapy (natalizumab, ocrelizumab, ofatumumab, cladribine)
   • Consider AHSCT for patients <45 years with inflammatory activity who fail high-efficacy DMTs

4. For primary progressive MS:

   • Ocrelizumab is the only approved option

5. For all patients:

   • Assess treatment response regularly
   • Consider switching therapy if breakthrough disease activity occurs

The treatment landscape for MS has evolved significantly, with multiple effective options available that can substantially reduce disease activity and improve quality of life when appropriately selected based on MS subtype, disease activity, and individual patient factors.