Multiple Sclerosis Treatment
Initial Treatment for Relapsing Forms of MS
For newly diagnosed relapsing-remitting MS, initiate treatment with interferon beta-1a (30 mcg intramuscularly weekly) or interferon beta-1b (subcutaneously every other day), as these first-line disease-modifying therapies have established long-term safety profiles and proven efficacy in reducing relapse rates and slowing disability progression. 1, 2, 3
First-Line Disease-Modifying Therapies
The initial treatment landscape includes several options with distinct administration routes:
Interferon beta preparations remain important first-line options due to their established 25+ year safety track record and proven efficacy 2, 4
- Intramuscular IFNβ-1a: 30 mcg weekly reduces annual exacerbation rate from 0.90 to 0.61 and delays sustained disability progression (21.9% vs 34.9% at 2 years) 3
- Subcutaneous IFNβ-1a and IFNβ-1b: administered 3 times weekly or every other day 2
- Peginterferon beta-1a: extended half-life formulation requiring only once every 2 weeks administration, potentially improving adherence 2
Glatiramer acetate (20 mg subcutaneously daily) provides comparable efficacy to interferons with a different mechanism targeting myelin basic protein mimicry 4, 5
Oral therapies (fingolimod, teriflunomide, dimethyl fumarate) offer convenience but lack long-term postmarketing safety data compared to injectables 4
Managing First-Line Therapy Adverse Effects
Flu-like syndrome with interferons occurs commonly but can be effectively managed:
- Initiate dose escalation gradually over the first month 6
- Administer ibuprofen or acetaminophen prophylactically 30 minutes before injection and for 24 hours after 6
- Inject before bedtime to sleep through symptoms 6
Injection site reactions require proactive management:
- Rotate injection sites systematically 6
- Apply ice before injection and warm compresses afterward 6
- Monitor for skin necrosis with subcutaneous formulations 6
Hepatotoxicity monitoring: Check liver function tests at baseline, monthly for 3 months, then every 3-6 months during interferon therapy 6
Secondary Treatment Options
High-Efficacy Therapies for Inadequate Response
When patients experience breakthrough disease activity (new relapses, new/enlarging T2 lesions, or gadolinium-enhancing lesions) on first-line therapy, escalate to natalizumab (300 mg IV every 4 weeks) if JC virus antibody-negative, or consider alemtuzumab, ocrelizumab, or fingolimod. 7, 8, 4
Natalizumab Protocol
- Indication: Relapsing forms of MS with inadequate response to first-line therapies 8
- Dosing: 300 mg intravenous infusion over 1 hour every 4 weeks 8
- Critical safety monitoring:
Monoclonal Antibodies
- Alemtuzumab: Targets CD52, highly efficacious but carries risk of secondary autoimmune disorders 4
- Ocrelizumab/Ofatumumab: Anti-CD20 agents with favorable efficacy-safety profiles 4
Autologous Haematopoietic Stem Cell Transplantation (AHSCT)
For aggressive relapsing-remitting MS refractory to high-efficacy disease-modifying therapies, AHSCT using intermediate-intensity conditioning (cyclophosphamide-ATG or BEAM-ATG) is recommended as it achieves superior disease control compared to continued DMT escalation. 9, 7
AHSCT Eligibility Criteria
Based on ongoing randomized trials (RAM-MS, BEAT-MS, STAR-MS, NET-MS) 9:
- Age 18-55 years 9
- EDSS score 0.0-6.0 9
- Active disease: ≥1 relapse AND MRI activity (gadolinium-enhancing or new T2 lesions) in past 12 months despite DMT 9
- Failed standard or high-efficacy DMT for ≥6 months 9
AHSCT Conditioning Regimens
- Cyclophosphamide-ATG: Most commonly used over past 10 years, easier inpatient management 9
- BEAM-ATG: Carmustine, etoposide, cytarabine, melphalan with anti-thymocyte globulin 9
- Avoid low-intensity regimens (low-dose cyclophosphamide without serotherapy) due to poor efficacy 9
- Avoid high-intensity myeloablative protocols (busulfan-cyclophosphamide-ATG) outside clinical trials due to excessive toxicity 9
Pre-AHSCT Requirements
Comprehensive screening must include 7:
- Liver function, bone marrow, viral profiles (HIV, hepatitis B/C, CMV, EBV, VZV)
- Glomerular filtration rate and lung function testing
- Cardiac assessment: ECG and echocardiography
- Dental evaluation and treatment of active infections
- Fertility counseling and preservation options
- Psychological assessment
Post-AHSCT Rehabilitation
Rehabilitation should begin immediately post-AHSCT to exploit the brain's reorganizational capacity during complete inflammatory suppression. 9
- Phase 1 (weeks -4 to 0): Pre-habilitation to optimize physical and respiratory function 9
- Phase 2 (weeks 0-4): Inpatient early mobilization and respiratory exercises 9
- Phase 3 (months 1-6): Intensive outpatient rehabilitation targeting identified impairments 9
- Phase 4 (months 6+): Maintenance rehabilitation and community reintegration 9
Progressive MS Considerations
For secondary progressive MS with continued inflammatory activity (gadolinium-enhancing lesions), consider:
- IFNβ-1b: Demonstrated slowing of progression independent of baseline disability 5
- Mitoxantrone: Effective but limited by cumulative cardiotoxicity (maximum lifetime dose constraints) 6, 5
- AHSCT: May be considered in early secondary progressive MS with ongoing inflammation 9
Primary progressive MS has limited treatment options and should be distinguished from secondary progressive MS, as response rates differ significantly. 9
Monitoring Protocol
Standard MRI Surveillance
- Baseline: 1.5T minimum field strength, slice thickness ≤3mm, T2-weighted, T2-FLAIR, and gadolinium-enhanced T1-weighted sequences 7
- Follow-up frequency 7:
- High-risk patients (active disease, recent escalation): Every 3-4 months
- Stable patients: Every 6 months in first year, then annually
- Maintain consistent protocols across serial scans to facilitate comparison 7
Clinical Monitoring
- Cognitive assessment: Symbol Digit Modalities Test (SDMT) at baseline and every 6 months 7
- EDSS scoring: Document at each visit to detect sustained disability progression 9
- Relapse documentation: Distinguish true relapses from pseudorelapses (infection, heat) 7
Critical Pitfalls to Avoid
- Do not unnecessarily prolong DMT withdrawal before AHSCT, as this increases relapse risk 7
- Do not underestimate carryover effects of alemtuzumab (lymphodepletion persists 12+ months) before AHSCT 7
- Do not rely on imaging alone—clinical assessment remains essential for treatment decisions 7
- Do not continue ineffective therapy—early escalation prevents irreversible disability accumulation 4, 5
- Do not use natalizumab in JC virus antibody-positive patients without careful risk-benefit discussion given PML risk 8