What are the treatment options for multiple sclerosis?

Treatment Options for Multiple Sclerosis

Disease-modifying therapies (DMTs) are the cornerstone of multiple sclerosis treatment, with high-efficacy options such as natalizumab, ocrelizumab, and ofatumumab recommended for highly active disease, reducing annual relapse rates by 29-68% compared to placebo. 1

Disease-Modifying Therapies by MS Subtype

Relapsing Forms of MS (including clinically isolated syndrome, relapsing-remitting, and active secondary progressive)

First-Line Options:

• Injectable therapies:
  • Interferon beta preparations (IFNβ-1a, IFNβ-1b, peginterferon beta-1a) 2, 3
    • Administration: Subcutaneous or intramuscular, frequency varies from every other day to once every 2 weeks
    • Common side effects: Injection site reactions, flu-like symptoms
  • Glatiramer acetate

Higher-Efficacy Options (for highly active disease or inadequate response to first-line):

• Oral therapies:

  • Sphingosine 1-phosphate receptor modulators
  • Fumarates
  • Teriflunomide
  • Cladribine (Mavenclad) - for highly active relapsing MS 1

• Monoclonal antibodies:

  • Natalizumab (Tysabri) 4
    • Dosage: 300 mg intravenous infusion over one hour every four weeks
    • Important risk: Progressive multifocal leukoencephalopathy (PML)
    • Risk stratification: Based on JCV antibody status and index
  • Ocrelizumab
  • Ofatumumab

Primary Progressive MS

• Ocrelizumab - the only FDA-approved option for primary progressive MS 1

Treatment Selection Algorithm

1. Determine MS subtype:

   • Relapsing-remitting MS (RRMS)
   • Secondary progressive MS (SPMS) with activity
   • Primary progressive MS (PPMS)
   • Clinically isolated syndrome (CIS)

2. Assess disease activity:

   • Clinical relapses
   • MRI activity (new/enlarging T2 lesions, gadolinium-enhancing lesions)
   • Disability progression

3. Consider patient factors:

   • Age
   • Pregnancy planning
   • Comorbidities
   • Risk tolerance

4. Treatment initiation:

   • For mild-moderate RRMS: Start with injectable therapies (interferons or glatiramer acetate)
   • For highly active RRMS or SPMS with activity: Consider high-efficacy options (natalizumab, ocrelizumab, ofatumumab)
   • For PPMS: Ocrelizumab
   • For CIS: Early intervention with injectable therapies

5. Monitoring and follow-up:

   • Regular clinical assessment using Expanded Disability Status Scale (EDSS)
   • Annual brain MRI with standardized protocol 1
   • JCV antibody testing every 6 months for patients on natalizumab 1

Monitoring Recommendations

Clinical Monitoring

• Regular assessment using Expanded Disability Status Scale (EDSS)
• Consider combining EDSS with Multiple Sclerosis Functional Composite (MSFC) for better sensitivity
• Systematic assessment of cognitive outcomes
• Collection of patient-reported outcomes including fatigue and quality of life measures 1

Imaging Monitoring

• Annual brain MRI is recommended for all MS patients
• MRI protocol should include:
  • T2-weighted FLAIR sequences
  • T2-weighted fast/turbo spin echo sequences
  • Gadolinium-enhanced T1-weighted sequences
  • Diffusion-weighted imaging (for patients at risk of PML) 1

Special Considerations

Risk Management for Natalizumab

• PML risk is stratified by anti-JCV antibody status
• JCV antibody testing should be performed every 6 months
• MRI surveillance frequency depends on JCV antibody status and index 1

Vaccination Recommendations

• Complete hepatitis B vaccination before starting potent MS therapy
• Administer vaccines 4-6 weeks before starting or 4-6 months after ending certain treatments
• No concurrent use of live vaccines
• Recommended vaccines: COVID-19, shingles, flu, and RSV 1

Treatment for Refractory Cases

For patients who fail to respond to conventional DMTs, autologous hematopoietic stem cell transplantation (AHSCT) may be considered in the following cases:

• 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

Common Pitfalls and Caveats

1. Delayed treatment initiation: Early identification and treatment during the first 2-10 years of symptom onset is critical to prevent long-term disability.

2. Underestimating subclinical disease activity: Regular MRI monitoring is essential even in the absence of clinical symptoms.

3. Inadequate risk stratification: Particularly for natalizumab, where PML risk varies significantly based on JCV antibody status.

4. Inappropriate treatment selection: Matching treatment intensity to disease activity is crucial for optimal outcomes.

5. Insufficient monitoring: Regular clinical and MRI monitoring is essential to detect breakthrough disease activity early.

The evidence strongly supports early intervention with appropriate DMTs based on disease subtype and activity level, with regular monitoring to assess treatment response and detect potential complications.