Best Treatments for Multiple Sclerosis
Primary Recommendation
For relapsing-remitting MS with highly active disease that has failed high-efficacy disease-modifying therapy, autologous haematopoietic stem cell transplantation (AHSCT) is the most effective treatment, demonstrating 87% progression-free survival at 10 years and is now endorsed as standard of care rather than a last resort. 1, 2
Treatment Algorithm by Disease Subtype and Activity
Relapsing-Remitting MS (RRMS)
First-Line Treatment:
- Start with high-efficacy DMTs immediately rather than moderate-efficacy options: ocrelizumab, ofatumumab, natalizumab, alemtuzumab, or cladribine 1, 2
- Early aggressive treatment yields superior long-term outcomes compared to traditional stepped-care approaches 1, 2
- Natalizumab is FDA-approved for relapsing forms of MS including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease 3
- Dimethyl fumarate is FDA-approved for relapsing forms of MS 4
Escalation to AHSCT:
- Consider AHSCT after failure of a single high-efficacy DMT if aggressive features are present (frequent relapses, incomplete recovery, high MRI lesion frequency, rapid disability onset) 1, 2
- Refer patients with highly active, treatment-refractory MS as early as possible for AHSCT evaluation 1
Secondary Progressive MS (SPMS)
AHSCT is indicated ONLY for early inflammatory active disease with ALL of the following criteria: 1, 2
- Clinical or MRI inflammatory activity documented within past 12 months
- EDSS score <6.0
- Age <45 years
- Disease duration <10 years
If AHSCT criteria not met:
- No specific FDA-approved therapies exist for non-inflammatory SPMS
- Continue monitoring for inflammatory activity that might change eligibility
Primary Progressive MS (PPMS)
Ocrelizumab is the only FDA-approved DMT specifically for primary progressive MS, though efficacy is limited to slowing disability progression. 2, 5, 6
AHSCT may be considered only if: 1, 2
- Early inflammatory active disease present
- EDSS <6.0
- Age <45 years
- Short disease duration
- Documented clinical and radiological inflammatory activity
Optimal AHSCT Candidate Profile
The European Society for Blood and Marrow Transplantation defines optimal candidates as: 1, 2
- Age <45 years (NOT recommended if >55 years)
- Disease duration <10 years (NOT recommended if >20 years)
- EDSS score <4.0 (NOT recommended if >6.0)
- High focal inflammation present (NOT recommended if absent)
- Relapsing-remitting MS subtype
- Failed ≥1 high-efficacy DMT after meaningful treatment period
- No major cognitive impairment
Long-term outcomes: 2
- 87% progression-free survival at 10 years in optimal candidates
- 71% progression-free survival at 10 years for relapsing-remitting MS
- 1.4% transplant-related mortality
Critical Exclusion Criteria for AHSCT
Absolute contraindications: 1, 2
- Age >55 years
- EDSS >6.0
- Absence of focal inflammation
- No inflammatory activity in past 12 months
- Major cognitive impairment
- Secondary progressive MS without inflammatory activity
- Primary progressive MS without early inflammatory features
Monitoring Protocol
High-risk patients (highly active disease, recent treatment change): 2, 7
- MRI surveillance every 3-4 months
- Include T2-weighted, T2-FLAIR, and gadolinium-enhanced T1-weighted sequences
- MRI every 6 months in first year
- Then annually if stable
- Maintain consistent protocols for serial comparison
Critical pitfall to avoid: 7
- Pseudoatrophy effect causes excessive brain volume decrease within first 6-12 months of treatment due to resolution of inflammation—this should NOT be mistaken for disease progression
Treatment Failure Criteria
Breakthrough disease is defined as: 2, 5
- ≥1 clinical relapse occurring ≥3 months after DMT initiation
- New MRI activity (new T2 lesions or gadolinium-enhancing lesions)
- Incomplete recovery from relapses
- Continued disability progression despite treatment
Age-Specific Considerations
Patients <45 years with disease duration <10 years: 5
- Optimal candidates for intensive treatments including AHSCT if indicated
- Should continue therapy even if currently stable if history of highly active disease
Patients >55 years with stable disease: 7
- Consider treatment discontinuation
- Risk of infections and adverse effects may outweigh benefits of continued immunosuppression
Post-AHSCT Rehabilitation
Rehabilitation must begin immediately after AHSCT to exploit neuroplasticity during complete inflammatory suppression: 7
- Pre-habilitation phase before transplant
- Early mobilization during recovery
- Intensive outpatient rehabilitation
- Maintenance rehabilitation long-term
Common Pitfalls to Avoid
Delayed referral for AHSCT: 1
- Patients should be referred early when treatment-refractory disease is identified, not as a last resort after extensive disability accumulation
Inappropriate washout periods: 5
- Carryover effects between different DMTs can cause complications
- Specific washout protocols must be followed when switching therapies
Misinterpreting pseudoatrophy: 7
- Brain volume loss in first 6-12 months on DMT reflects inflammation resolution, not progression
- Do not switch therapies based on this finding alone
Using AHSCT in wrong population: 1, 2
- AHSCT is NOT appropriate for non-inflammatory progressive MS
- AHSCT is NOT appropriate for patients with EDSS >6.0 or age >55 years
- AHSCT requires documented inflammatory activity within past 12 months for progressive forms