What is the recommended treatment for a patient with relapsing-remitting multiple sclerosis?

Treatment of Relapsing-Remitting Multiple Sclerosis

For relapsing-remitting multiple sclerosis, initiate disease-modifying therapy (DMT) with either interferon beta formulations, glatiramer acetate, or oral agents as first-line options, with escalation to high-efficacy infusion therapies (natalizumab, ocrelizumab, or alemtuzumab) reserved for patients with highly active disease or breakthrough activity on standard therapy. 1, 2

First-Line Disease-Modifying Therapies

Injectable Therapies

• Interferon beta formulations are FDA-approved for relapsing forms of MS and reduce annual relapse rates by 29-68% compared to placebo 3, 4, 5

  • Subcutaneous interferon beta-1a (3 times weekly) 4
  • Intramuscular interferon beta-1a (weekly) 4, 6
  • Subcutaneous interferon beta-1b (every other day) 7
  • Peginterferon beta-1a (every 2 weeks) offers less frequent dosing with similar efficacy 7, 8

• Glatiramer acetate is an alternative first-line injectable option with comparable efficacy to interferons 9, 5

Common Adverse Effects of Injectables

• Flu-like symptoms and injection site reactions are the most frequent side effects 7, 8
• Patient education and mitigation strategies are essential for adherence 7
• Switching between interferon formulations is viable if tolerability issues arise 7, 8

Oral Therapies

• Fingolimod (sphingosine 1-phosphate receptor modulator) is FDA-approved for relapsing MS in patients ≥10 years old 3
• Teriflunomide and fumarates are additional oral first-line options 5
• Cladribine represents an oral high-efficacy option 5

High-Efficacy Escalation Therapies

When to Escalate

• Escalate to high-efficacy DMT for patients with highly active MS who have failed standard DMT for ≥6 months 1
• Consider escalation for breakthrough disease activity (new relapses or MRI lesions) on first-line therapy 1, 2

Infusion Therapy Options

Natalizumab (300 mg IV every 4 weeks):

• Recommended as escalation therapy for breakthrough disease, particularly in JC virus antibody-negative patients 1, 10
• Critical warning: Increases risk of progressive multifocal leukoencephalopathy (PML), an often fatal brain infection 10
• Risk factors for PML include: anti-JCV antibody positivity, duration of therapy >2 years, and prior immunosuppressant use 10
• Available only through TOUCH® Prescribing Program REMS 10
• Monitor for any new neurological symptoms suggestive of PML with MRI and CSF analysis when indicated 10

Ocrelizumab:

• Approved for both relapsing-remitting MS and primary progressive MS 1
• The only FDA-approved treatment specifically for primary progressive disease 1

Alemtuzumab:

• High-efficacy DMT option for escalation in highly active MS 1
• Associated with secondary autoimmune adverse effects including thyroid disease 5

Monitoring Disease Activity

MRI Surveillance Protocol

• Obtain initial MRI at 3-6 months after starting DMT to establish baseline disease activity 2
• For active disease: perform MRI every 6 months for the first 1-2 years 2
• Transition to annual MRI once disease is stable 2
• Use consistent protocols with T2-weighted sequences and gadolinium enhancement 2

Interpreting MRI Results

• New non-enhancing T2 lesions indicate active disease and warrant treatment intensification 2
• New T2 lesions on 6-12 month follow-up do not automatically indicate treatment failure but require clinical correlation 11

Advanced Treatment Options

Autologous Hematopoietic Stem Cell Transplantation (AHSCT)

• Consider AHSCT for aggressive relapsing-remitting MS refractory to high-efficacy DMTs 1, 2
• Optimal candidates: Age <45 years, disease duration <5 years, recent inflammatory activity on MRI, lower EDSS scores 2
• Outcomes: 80-100% progression-free survival, 70-80% achieve no evidence of disease activity (NEDA) 2
• Long-term data shows 87% progression-free survival at 10 years with 1.4% transplant-related mortality 2
• Use intermediate-intensity conditioning regimens 1

Acute Relapse Management

Corticosteroid Treatment

• Administer high-dose corticosteroids (methylprednisolone or ACTH) to hasten recovery from acute relapses 9
• Monitor nutritional intake and ensure adequate hydration during treatment 11

Rehabilitation During Relapse

• Implement four-phase rehabilitation approach 11:
  • Phase 1 (Pre-treatment): Enhance neuromuscular and respiratory function
  • Phase 2 (Weeks 0-4): Gentle mobilization when medically stable; contraindicate exercise if platelets <20 × 10⁹/L
  • Phase 3 (Weeks 8-12): More intense physical therapy
  • Phase 4 (Weeks 12-26): Community rehabilitation for independence

Nutritional Considerations

• Do not rely on vitamin D supplementation alone to manage relapses—studies show inconsistent results in reducing relapse rates 12, 11
• Vitamin D doses studied ranged from 10,000-40,000 IU weekly with no significant difference in annualized relapse rates versus placebo 12
• Consider omega-6 fatty acid supplementation (may decrease relapse severity), but avoid omega-3 supplementation (no proven benefit) 11

Important Safety Considerations

Contraindications and Warnings

• Never combine natalizumab with immunosuppressants due to increased PML risk 10
• Adverse effects across DMT classes include infections, bradycardia, heart blocks, macular edema, infusion reactions, and secondary autoimmune conditions 5
• Life expectancy with MS is reduced (75.9 vs 83.4 years in general population) 5

Monitoring Requirements

• Regular clinical assessments for new neurological symptoms 10
• Surveillance for infections, particularly with high-efficacy therapies 5
• JC virus antibody testing before and during natalizumab therapy 10