What Are Disease-Modifying Therapies (DMTs)?
Disease-Modifying Therapies, or DMTs, are a class of medications used to treat multiple sclerosis (MS) [1.5.2]. Unlike treatments that only manage symptoms, the primary goals of DMTs are to reduce the frequency and severity of relapses, slow the accumulation of disability, and limit new inflammatory activity in the central nervous system (CNS) [1.5.4]. Research indicates that early and ongoing treatment with a DMT is the most effective strategy for managing the long-term course of MS [1.8.1]. There are more than 20 FDA-approved DMTs, which can be classified in several ways, most commonly by their administration route or their efficacy level [1.4.4].
Types of DMTs by Administration Route
The most common way to group DMTs is by how they are taken. This often plays a significant role in treatment decisions, balancing efficacy with patient lifestyle and convenience [1.8.1].
Injectable DMTs
For many years, self-injected medications were the primary treatment for MS. These drugs have a long track record of safety and moderate efficacy [1.3.6]. They generally work by modulating the immune system to reduce inflammation [1.5.2].
- Interferons: This class includes drugs like Avonex, Betaseron, Plegridy, and Rebif [1.2.1]. They are thought to work by reducing the inflammatory response that occurs in MS [1.5.2]. Common side effects include flu-like symptoms and injection-site reactions [1.6.2, 1.6.4].
- Glatiramer Acetate (Copaxone): This synthetic protein mimics a component of myelin and is believed to induce immune cells that reduce CNS inflammation [1.5.2]. It is also administered via self-injection [1.2.5].
- Ofatumumab (Kesimpta): A newer injectable medication, Kesimpta is a high-efficacy monoclonal antibody that works by depleting B cells, a type of white blood cell involved in MS inflammation. It is self-injected monthly [1.5.2, 1.2.6].
Oral DMTs
The introduction of oral DMTs offered a more convenient option for many patients. These daily or twice-daily pills have various mechanisms of action and efficacy levels [1.3.2].
- S1P Receptor Modulators: This class includes fingolimod (Gilenya), siponimod (Mayzent), ozanimod (Zeposia), and ponesimod (Ponvory) [1.2.1]. They work by trapping certain white blood cells (lymphocytes) in the lymph nodes, preventing them from entering the CNS and causing damage [1.5.2].
- Fumarates: Dimethyl fumarate (Tecfidera), diroximel fumarate (Vumerity), and monomethyl fumarate (Bafiertam) fall into this category [1.2.1]. They are thought to activate a pathway that helps limit inflammation and cellular damage [1.5.2]. Flushing and gastrointestinal issues are common side effects [1.5.6].
- Other Oral Agents: Other notable oral DMTs include teriflunomide (Aubagio), which blocks the proliferation of specific T and B cells, and cladribine (Mavenclad), a short-course therapy that temporarily reduces T and B lymphocyte counts [1.5.2].
Infused DMTs
Infused DMTs are administered directly into a vein (IV), typically in a clinical setting. This category includes some of the highest-efficacy treatments available [1.4.2]. Infusions are given on schedules ranging from every four weeks to once every six months, or even in yearly cycles [1.2.2].
- Anti-CD20 Monoclonal Antibodies: This powerful class of drugs targets and depletes B cells. It includes ocrelizumab (Ocrevus), rituximab (used off-label), and ublituximab (Briumvi) [1.3.3]. Ocrevus is notably the only DMT approved for primary progressive MS (PPMS) in addition to relapsing forms [1.2.6].
- Natalizumab (Tysabri): This high-efficacy therapy works by blocking certain immune cells from crossing the blood-brain barrier into the CNS [1.5.2]. It is given as a monthly infusion [1.2.2].
- Alemtuzumab (Lemtrada): This is an immune reconstitution therapy given in two yearly courses that depletes T and B lymphocytes [1.5.2]. Due to its risk profile, it is generally reserved for patients who have not responded to other DMTs [1.2.6].
Comparison of Common DMTs
| Drug Name (Brand) | Administration Route | General Mechanism | Common Side Effects |
|---|---|---|---|
| Interferon Beta-1a (Avonex) | Injection | Reduces inflammatory processes of the immune system [1.5.2] | Flu-like symptoms, injection site reactions [1.6.2] |
| Dimethyl Fumarate (Tecfidera) | Oral | Activates a pathway to reduce inflammation and oxidative stress [1.5.2, 1.5.3] | Flushing, nausea, diarrhea [1.5.6] |
| Fingolimod (Gilenya) | Oral | Traps lymphocytes in lymph nodes, preventing CNS entry [1.5.2] | Headache, slowed heart rate (first dose), increased infection risk [1.6.5] |
| Ocrelizumab (Ocrevus) | Infusion | Depletes B cells, a key part of the inflammatory attack in MS [1.5.2] | Infusion reactions, upper respiratory infections [1.9.3] |
| Natalizumab (Tysabri) | Infusion | Prevents immune cells from crossing the blood-brain barrier [1.5.2] | Headache, fatigue, increased risk of PML (a rare brain infection) [1.9.3] |
Choosing the Right DMT
Selecting a DMT is a personalized decision made in partnership with a neurologist [1.8.1]. Key factors include:
- Efficacy: DMTs are often categorized as moderate or high efficacy. Treatment strategies may involve starting with a moderate-efficacy drug and escalating if needed, or starting with a high-efficacy therapy from the beginning, especially for more active disease [1.3.6].
- Safety and Side Effects: Each drug has a unique risk profile that must be weighed against its benefits [1.6.5]. This includes common side effects and rare but serious risks like Progressive Multifocal Leukoencephalopathy (PML) associated with certain drugs [1.6.5].
- Lifestyle and Convenience: The method and frequency of administration (daily pill vs. twice-yearly infusion) are major considerations for patients [1.8.1].
- Disease Type: Most DMTs are approved for relapsing forms of MS (CIS, RRMS, and active SPMS), while only Ocrevus is approved for PPMS [1.2.6].
Conclusion
The landscape of multiple sclerosis treatment has been transformed by the development of numerous Disease-Modifying Therapies. With options ranging from self-injections and daily pills to high-efficacy infusions, patients and their healthcare providers can tailor treatment to an individual's specific disease activity, safety considerations, and lifestyle preferences [1.8.3]. The ongoing evolution of DMTs continues to offer new hope for better managing MS and slowing its progression.
Authoritative Link: National MS Society - Disease-Modifying Therapies
