From the Guidelines
For patients with active multiple sclerosis, autologous haematopoietic stem cell transplantation (AHSCT) should be considered as an escalation therapy for those with highly active MS and in whom high-efficacy disease-modifying therapies (DMTs) have failed, as recommended by recent guidelines from ECTRIMS and EBMT 1.
Key Considerations
- AHSCT has been endorsed as a standard of care for the treatment of relapsing–remitting MS that is refractory to conventional DMTs 1.
- High-efficacy DMTs, such as monoclonal antibodies (alemtuzumab, natalizumab, ocrelizumab, and ofatumumab), are more effective when treatment is initiated early 1.
- Treatment selection depends on disease severity, relapse frequency, MRI activity, patient preferences, and potential side effects.
Treatment Approach
- First-line options include injectable medications like interferon beta and glatiramer acetate, and oral medications such as fingolimod, dimethyl fumarate, and teriflunomide.
- For more aggressive MS, higher-efficacy options include natalizumab, ocrelizumab, or alemtuzumab.
- During acute relapses, high-dose corticosteroids like methylprednisolone are used to reduce inflammation and shorten symptom duration.
Comprehensive Management
- Comprehensive MS management also includes symptom-specific treatments for issues like fatigue, pain, and spasticity, along with physical therapy, occupational therapy, and psychological support.
- Development and adoption of risk scores and biomarkers to assist clinicians with prompt and robust selection of people who are eligible for AHSCT are encouraged 1.
From the FDA Drug Label
TYSABRI is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. REBIF is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
The treatment options for active multiple sclerosis (MS) include:
- Natalizumab (IV): indicated as monotherapy for the treatment of relapsing forms of MS, including active secondary progressive disease, in adults 2 2.
- Interferon beta-1a (SQ): indicated for the treatment of relapsing forms of MS, including active secondary progressive disease, in adults 3.
Key considerations:
- The expected benefit of treatment should be weighed against the potential risks, such as the risk of progressive multifocal leukoencephalopathy (PML) associated with natalizumab 2.
From the Research
Treatment Options for Active Multiple Sclerosis (MS)
The treatment of active multiple sclerosis (MS) involves the use of disease-modifying therapies (DMTs) that aim to reduce relapses and delay disability progression. Some of the key treatment options include:
- Intramuscular (IM) interferon (IFN) beta-1a (Avonex)
- Subcutaneous (SC) IFN beta-1a (Rebif)
- SC IFN beta-1b (Betaseron; Extavia)
- SC glatiramer acetate (Copaxone) 4
- Oral DMTs such as fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera) 4
- Monoclonal antibodies like alemtuzumab, daclizumab, and ocrelizumab 4, 5
Disease-Modifying Therapies (DMTs)
DMTs are classified into several classes, including:
- Interferons
- Glatiramer acetate
- Teriflunomide
- Sphingosine 1-phosphate receptor modulators
- Fumarates
- Cladribine
- Monoclonal antibodies 6 These DMTs have varying mechanisms of action and routes of administration, and their efficacy rates range from 29% to 68% in reducing annualized relapse rates compared to placebo or active comparators 6, 7
Treatment Approaches
There are two main treatment approaches for MS:
- Escalation approach: starting with a modestly effective DMT and escalating to a higher efficacy DMT when there is evidence of clinical and/or radiologic breakthrough activity 5, 8
- Early aggressive treatment approach: starting patients on a higher efficacy DMT early in the disease course 5 Clinical trials such as the TRaditional versus Early Aggressive Therapy for MS (TREAT-MS) trial and the Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the treatment of Relapsing-remitting MS (DELIVER-MS) trial are ongoing to compare these treatment strategies and their impact on clinical and radiologic outcomes 5
Efficacy and Acceptability of DMTs
A systematic review and network meta-analysis of randomized controlled trials compared the efficacy and acceptability of DMTs in patients with relapsing-remitting MS, and found that all DMTs were superior to placebo in reducing the relapse rate during the 2 years of follow-up 7 The study also found that alemtuzumab, ocrelizumab, natalizumab, and fingolimod had a relatively higher response and lower dropout rates than did the other DMTs 7