What medications are used to treat multiple sclerosis (MS)?

Medications for Multiple Sclerosis (MS)

Autologous hematopoietic stem cell transplantation (AHSCT) is recommended as an appropriate escalation therapy for people with highly active MS in whom high-efficacy disease-modifying therapy has failed. 1

First-Line Disease-Modifying Therapies (DMTs)

• Injectable therapies:

  • Interferon beta-1a (Avonex, Rebif) - reduces relapses and delays disability progression in relapsing forms of MS 2, 3
  • Interferon beta-1b (Betaseron, Extavia) - effective for relapsing forms of MS 3, 4
  • Glatiramer acetate (Copaxone) - reduces relapse rates by approximately 29% compared to placebo 3, 4
  • Peginterferon beta-1a - shown to reduce relapse rates compared to placebo 5

• Oral therapies:

  • Dimethyl fumarate (Tecfidera) - reduces relapses and new MRI lesions in relapsing forms of MS 6, 3
  • Teriflunomide (Aubagio) - primarily works by reducing new inflammatory lesion formation 7, 3
  • Fingolimod (Gilenya) - first FDA-approved oral DMT, reduces brain atrophy compared to placebo 8, 9
  • Cladribine - reduces brain atrophy compared to placebo 8, 5

High-Efficacy DMTs

• Monoclonal antibodies:
  • Natalizumab (Tysabri) - administered intravenously monthly, highly effective but associated with risk of progressive multifocal leukoencephalopathy (PML) 9, 5
  • Ocrelizumab - effective for both relapsing MS and primary progressive MS, reduces brain atrophy 8, 5
  • Alemtuzumab - shows superior efficacy in reducing annualized relapse rates compared to interferon beta-1a 8, 5
  • Rituximab and daclizumab - have shown beneficial results in clinical trials 10

Treatment Algorithm Based on MS Type

For Relapsing-Remitting MS:

1. Initial therapy: Start with injectable (interferons, glatiramer acetate) or oral (dimethyl fumarate, teriflunomide) DMTs based on patient factors 3, 4
2. If inadequate response: Escalate to higher-efficacy therapies like fingolimod, natalizumab, ocrelizumab, or alemtuzumab 1, 5
3. For highly active disease: Consider AHSCT after failure of high-efficacy DMT 1

For Progressive MS:

• Primary Progressive MS: Ocrelizumab is approved and shows efficacy 8, 3
• Secondary Progressive MS with inflammatory activity: Consider AHSCT only for those with early and inflammatory active disease 1

Considerations for AHSCT in MS

• AHSCT has shown superior efficacy compared to DMTs in selected patients with relapsing-remitting MS 1
• The MIST trial demonstrated superior progression-free survival at 5 years (90% vs 25%) for AHSCT compared to DMTs 1
• Recommended conditioning protocols include intermediate-intensity regimens such as BEAM-ATG or cyclophosphamide-ATG 1
• Patient selection is crucial - best results are seen in younger patients with shorter disease duration and fewer previous DMTs 1

Common Pitfalls and Considerations

• Treatment timing: Early treatment with high-efficacy DMTs is more effective than delayed treatment 1
• Monitoring: Regular monitoring for adverse effects is essential, particularly with higher-efficacy therapies 2, 6
• Vaccination: Vaccines should be administered 4-6 weeks before starting immunosuppressive therapies or 4-6 months after the last treatment course 8
• Pregnancy considerations: DMTs have varying pregnancy-related risks that must be considered for women of childbearing age 1
• Brain atrophy: Monitor for pseudoatrophy effect (excessive decrease in brain volume within first 6-12 months of treatment) which should not be mistaken for disease progression 8

Comparative Efficacy

• Network meta-analysis shows risk ratios for relapse reduction compared to placebo: alemtuzumab (0.49), ocrelizumab (0.49), natalizumab (0.51), fingolimod (0.57), dimethyl fumarate (0.65), teriflunomide 14mg (0.78), glatiramer acetate (0.80), and interferons (0.81-0.87) 5
• AHSCT has shown superior efficacy to high-efficacy DMTs in selected patients, with 5-year relapse-free survival of 85% versus 15% 1