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

Latest Treatments for Multiple Sclerosis

High-Efficacy Disease-Modifying Therapies as First-Line Treatment

For relapsing-remitting MS, initiate high-efficacy disease-modifying therapies (DMTs) immediately rather than using moderate-efficacy options or stepped escalation, as early aggressive treatment yields superior long-term outcomes. 1

• Start with ocrelizumab, ofatumumab, natalizumab, alemtuzumab, or cladribine as initial therapy for treatment-naive relapsing-remitting MS 1, 2
• This represents a paradigm shift from traditional stepped approaches, supported by real-world evidence demonstrating that delayed initiation of high-efficacy therapy results in worse long-term disability outcomes 3
• Interferon beta preparations (IFNβ-1a intramuscular, IFNβ-1a subcutaneous, IFNβ-1b subcutaneous) remain FDA-approved for relapsing forms of MS but are now considered moderate-efficacy options 4, 5

Autologous Hematopoietic Stem Cell Transplantation (AHSCT)

AHSCT represents the most effective escalation therapy for highly active relapsing-remitting MS that has failed high-efficacy DMTs, with 87% progression-free survival at 10 years in optimal candidates. 1, 2

Optimal Candidate Criteria for AHSCT

• Age <45 years 6, 1
• Disease duration <10 years 6, 1
• EDSS score <4.0 6, 1
• High focal inflammation on MRI 6, 1
• Failed ≥1 high-efficacy DMT after a meaningful treatment period 6, 1

When to Refer for AHSCT

• Refer patients with highly active, treatment-refractory MS immediately after failure of first high-efficacy DMT if aggressive disease features are present (frequent relapses ≥2/year, incomplete recovery from relapses, high frequency of new MRI lesions, rapid disability onset) 6, 1
• AHSCT as first-line therapy should only be considered for rapidly evolving, severe MS with poor prognosis, offered within a clinical trial or observational study 6

AHSCT Exclusion Criteria

• Age >55 years 6
• Disease duration >20 years 6
• EDSS score >6.0 6
• Absence of focal inflammation 6
• Multiple medical comorbidities 6
• Active infections 6
• Long-standing, advanced MS with severe disability carries high risk and low benefit 6

Treatment for Progressive MS

Secondary Progressive MS

• AHSCT can be considered only for young patients (<45 years) with early secondary progressive MS of short disease duration who have well-documented clinical and radiological evidence of active inflammatory disease 6, 1
• Patients must demonstrate clinical or MRI inflammatory activity within the past 12 months 6, 2
• AHSCT is not supported for progressive MS without detectable inflammatory lesion activity due to lack of evidence 6

Primary Progressive MS

• Ocrelizumab is the only FDA-approved DMT specifically indicated for primary progressive MS, though efficacy is limited to slowing disability progression 1, 2
• AHSCT may be considered only for early inflammatory active disease with EDSS <6.0 and age <45 years 2

MRI Monitoring Protocol

• Perform brain MRI at least annually for stable patients 1, 2
• Increase MRI frequency to every 3-4 months for high-risk patients (highly active disease, recent treatment changes, or those on natalizumab due to progressive multifocal leukoencephalopathy risk) 1, 3, 2
• Include T2-weighted and T2-FLAIR sequences for detecting new or enlarging lesions, and gadolinium-enhanced T1-weighted sequences to identify active inflammatory lesions 1, 2

Age-Based Treatment Considerations

• Continue aggressive DMT even if clinically stable, particularly if disease duration <10 years or history of highly active disease before stabilization 1, 3
• Consider discontinuing DMT in patients >55 years with stable disease, as infection risks and other adverse effects may outweigh benefits of continued immunosuppression 1, 3

Natalizumab-Specific Considerations

• Natalizumab is indicated as monotherapy for relapsing forms of MS in adults 7
• Natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection that usually leads to death or severe disability 7
• Risk factors for PML include presence of anti-JCV antibodies, duration of therapy, and prior use of immunosuppressants 7
• Natalizumab dosing should be withheld immediately at the first sign or symptom suggestive of PML 7
• Available only through a restricted REMS program called the TOUCH® Prescribing Program 7

Critical Pitfalls to Avoid

• Do not delay referral for AHSCT evaluation in patients with breakthrough disease on first high-efficacy DMT who have aggressive disease features — outcomes are significantly better when AHSCT is performed earlier in the disease course 6, 1, 3
• Do not offer AHSCT to patients with long-standing progressive MS without inflammatory activity — this population has high procedural risk with minimal benefit 6
• Do not use stepped escalation approaches starting with moderate-efficacy DMTs — this outdated strategy results in worse long-term disability outcomes compared to early high-efficacy therapy 1, 3

Post-AHSCT Rehabilitation

• Begin intensive rehabilitation immediately after AHSCT to exploit neuroplasticity during complete inflammatory suppression 1
• Use a phased approach including pre-habilitation, early mobilization, intensive outpatient rehabilitation, and maintenance rehabilitation 1