Treatment Options for Relapsing-Remitting Multiple Sclerosis (RMS)
For treatment-naïve patients with relapsing-remitting MS, high-efficacy therapies (HETs) such as ocrelizumab, ofatumumab, natalizumab, alemtuzumab, or cladribine should be initiated early to minimize neurological damage accumulation, rather than following traditional escalation approaches with interferon beta or glatiramer acetate. 1
High-Efficacy Therapies (First-Line Options)
Monoclonal Antibodies and Immune Reconstitution Therapies:
Natalizumab (Tysabri) is FDA-approved as monotherapy for relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, administered as 300 mg IV infusion every 4 weeks. 2 However, natalizumab carries significant PML risk that increases with anti-JCV antibody positivity, duration of therapy beyond 2 years, and prior immunosuppressant use. 2
Ocrelizumab and ofatumumab are anti-CD20 monoclonal antibodies that demonstrate superior efficacy in treatment-naïve RRMS patients, with emerging evidence supporting their use as first-line agents. 1
Alemtuzumab and cladribine represent immune reconstitution strategies that provide sustained disease control after limited treatment courses, particularly effective in early, active RRMS. 3, 1
Autologous hematopoietic stem cell transplantation (AHSCT) using cyclophosphamide + ATG or BEAM + ATG conditioning achieves 70-80% NEDA-3 rates and 80-100% progression-free survival in relapsing-remitting MS patients with recent inflammatory activity. 3 In Swedish cohorts of RRMS patients followed for 10 years, AHSCT achieved 87% progression-free survival with zero transplant-related mortality. 3
Moderate-Efficacy Therapies (Traditional First-Line)
Injectable Immunomodulators:
Interferon beta-1b (Betaseron) is FDA-approved for relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. 4
Interferon beta-1a and glatiramer acetate reduce relapse rates by approximately one-third and are indicated for mobile patients with at least two relapses in the past two years. 5 These agents demonstrate sustained efficacy for 4-6 years and reduce MRI measures of disease activity. 6
Critical Selection Criteria for AHSCT
Optimal Candidate Profile:
Age 18-55 years with relapsing-remitting MS and EDSS score 0.0-6.0. 3
Disease duration ≤10 years from diagnosis with recent inflammatory activity (one or more clinical relapse AND MRI activity in the previous 12 months). 3
MRI activity defined as one or more gadolinium-enhancing lesion OR one or more new T2 lesions. 3
Prior failure of standard DMTs (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, natalizumab) or monoclonal antibodies. 3
AHSCT demonstrates near-complete progression-free survival and disability improvement in patients aged <45 years with short disease duration (<5 years), clinically and radiologically active disease, and high brain lesion load. 3
Monitoring Requirements
MRI Surveillance Protocol:
For early relapsing-remitting MS with active inflammation, perform MRI every 6-12 months using gadolinium-DTPA enhancement to detect active inflammation. 3, 7
Approximately 80% of new lesions show gadolinium enhancement in relapsing-remitting MS, making contrast essential for detecting subclinical activity. 3, 8
For breakthrough disease or therapy escalation, increase MRI frequency to every 3-4 months. 7
Clinical assessments alone substantially underestimate true disease activity, as most inflammatory activity occurs asymptomatically. 7, 8
Common Pitfalls to Avoid
Treatment Delays:
The traditional escalation approach (starting with interferons/glatiramer acetate and escalating only after failure) allows accumulation of irreversible neurological damage that could be prevented with early HET initiation. 1
Disease activity varies dramatically between patients (1 to 207 active lesions over 6 months in untreated RRMS patients), making serial MRI monitoring essential rather than relying on clinical assessment alone. 3, 8
AHSCT Misconceptions:
AHSCT is no longer reserved for advanced, progressive MS—contemporary practice focuses on relapsing-remitting MS with recent inflammatory activity, where outcomes are dramatically superior (71-87% progression-free survival at 10 years versus 33-57% in progressive MS). 3
Transplant-related mortality has decreased from 2.8% in early cohorts with advanced disease to 0-1.4% in contemporary RRMS cohorts. 3
Natalizumab Safety: