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

Multiple Sclerosis Management: Treatment Options

The management of multiple sclerosis (MS) should follow a stepped approach using disease-modifying therapies (DMTs) based on disease subtype and activity, with autologous hematopoietic stem cell transplantation (AHSCT) reserved for cases refractory to high-efficacy DMTs. 1

Disease-Modifying Therapies (DMTs)

First-Line Therapies

• Interferon beta preparations:

  • FDA-approved for relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease 2
  • Available formulations include subcutaneous (SC) IFNβ-1b, SC IFNβ-1a, intramuscular IFNβ-1a, and SC peginterferon beta-1a (requires less frequent administration) 3
  • Reduce relapse rates by 29-68% compared to placebo 1
  • Common adverse effects: injection site reactions and flu-like symptoms 3

• Glatiramer acetate:

  • Alternative first-line option for relapsing forms of MS
  • Similar efficacy profile to interferons 4

• Teriflunomide:

  • Oral first-line option 4

High-Efficacy Therapies

• Natalizumab:

  • Indicated as monotherapy for relapsing forms of MS 5
  • Recommended for patients with highly active disease 1
  • Risk of progressive multifocal leukoencephalopathy (PML) necessitates:
    • JCV antibody testing every 6 months
    • Risk stratification based on anti-JCV antibody status and index
    • Regular MRI surveillance 1
    • Available only through a restricted TOUCH® Prescribing Program 5

• Ocrelizumab:

  • High-efficacy option for relapsing MS
  • Only FDA-approved option for primary progressive MS 1

• Ofatumumab:

  • High-efficacy option for relapsing forms of MS 1

• Cladribine (Mavenclad):

  • Deoxyadenosine analogue prodrug that preferentially depletes lymphocytes
  • Effective in highly active relapsing MS 1

Advanced Treatment Option: AHSCT

Autologous hematopoietic stem cell transplantation (AHSCT) has shown promising results in specific MS populations:

• Candidates for AHSCT:

  • Young patients (<45 years) with early disease showing inflammatory activity
  • Patients who have failed ≥1 high-efficacy DMT with poor prognostic factors
  • Patients with increasing EDSS scores despite treatment 1

• Evidence supporting AHSCT:

  • MIST trial showed 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 (No Evidence of Disease Activity) at 5 years 1

• AHSCT protocol includes four rehabilitation phases:

  1. Pre-habilitation (before transplantation)
  2. Acute rehabilitation (weeks 0-4)
  3. Subacute rehabilitation (weeks 8-12)
  4. Community rehabilitation (weeks 12-26) 6

Monitoring and Follow-up

• MRI monitoring:

  • Annual brain MRI recommended to assess disease activity even without clinical symptoms 1
  • Follow-up MRI 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

• Clinical monitoring:

  • Regular assessment using Expanded Disability Status Scale (EDSS)
  • Consider combining EDSS with Multiple Sclerosis Functional Composite (MSFC) for better sensitivity 6
  • Cognitive outcomes should be systematically assessed 6
  • Patient-reported outcomes including fatigue and quality of life measures should be collected 6

Treatment of Relapses

• Corticosteroids:
  • Intravenous methylprednisolone is the standard treatment for acute relapses 4
  • Monthly pulsed methylprednisolone (1g IV) can be considered as add-on therapy to interferon beta or glatiramer acetate to reduce relapse rates 7

Special Considerations

• Vaccination:

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

• Treatment discontinuation:

  • Monitor for Immune Reconstitution Inflammatory Syndrome (IRIS) if treatment is discontinued 1
  • For MS reactivation after AHSCT, management should be individualized 6

• Pregnancy considerations:

  • Interferon beta-1a remains an important therapeutic option around pregnancy planning and lactation 8

Importance of Early Intervention

Early identification and treatment during the first 2-10 years of symptom onset is critical to prevent long-term disability and improve patient outcomes. Delaying treatment or underestimating subclinical disease activity can lead to worse outcomes 1.