Disease-modifying therapies for multiple sclerosis
Fact-checked by Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are medications that can change the course of the disease by reducing disease activity and/or slowing the accumulation of disability over time.
In MS, the immune system launches an inflammatory attack in the brain and spinal cord, damaging the protective myelin sheath that surrounds nerve fibers and helps them transmit electrical signals efficiently. This damage disrupts communication between the brain and the rest of the body, giving rise to the disease’s symptoms.
All currently approved DMTs essentially work by dampening the activity of the immune system to reduce the inflammation that drives MS. By limiting these inflammatory attacks, DMTs can help prevent new lesions from forming, lower the risk of relapses, and slow the accumulation of disability.
Notably, DMTs cannot repair existing nerve damage or reverse symptoms that have already developed. For this reason, it is generally recommended that MS patients start treatment with a DMT as early as possible to help preserve neurological function and delay long-term disability.
DMT approval by MS type
When regulatory agencies approve a DMT, the approval specifies which types of MS the medication is indicated to treat. MS is generally categorized into four main types:
- clinically isolated syndrome (CIS)
- relapsing-remitting MS (RRMS)
- secondary progressive MS (SPMS)
- primary progressive MS (PPMS)
MS can also be described as active or nonactive, depending on whether a person experiences relapses or shows signs of ongoing disease activity on MRI scans.
In the U.S., more than 20 DMTs are approved for treating relapsing forms of MS, which include CIS, RRMS, and active SPMS. These medications primarily work by reducing the active inflammation that drives relapses and lesion formation.
By contrast, nonrelapsing forms of the disease — such as PPMS and nonactive SPMS — are mainly driven by chronic inflammation in the brain and spinal cord that causes the gradual loss of nerve cells. Most current medications are unable to effectively target this “smoldering” inflammation, making progressive MS types more difficult to treat.
In the U.S., Ocrevus and Ocrevus Zunovo are approved for treating PPMS, while mitoxantrone remains the only therapy theoretically approved for nonactive SPMS. However, mitoxantrone is now rarely used due to its risk of serious side effects, including heart damage and blood cancers.
Approved DMTs
More than 20 DMTs are currently approved for the treatment of MS in the U.S. These medications differ in how often they are taken, how they work to control the disease, and how they are administered. DMTs are commonly grouped as injection, oral, or infusion therapies.
DMTs administered by injection
All injectable therapies are approved for treating relapsing forms of MS, including CIS, RRMS, and active SPMS. They differ mainly in how often and where they are injected.
- Avonex (interferon beta-1a): Given as a weekly intramuscular, or into-the-muscle, injection.
- Betaseron (interferon beta-1b): Administered via subcutaneous injections, or under the skin, every other day.
- Copaxone (glatiramer acetate injection): Injected subcutaneously either once daily or three times per week. Generic forms of this medication are available.
- Extavia (interferon beta-1b): A bioequivalent version of Betaseron with a similar dosing regimen.
- Kesimpta (ofatumumab): Self-administered once monthly as a subcutaneous injection.
- Ocrevus Zunovo (ocrelizumab and hyaluronidase-ocsq): Administered as a 10-minute subcutaneous injection once every six months. It is also approved for PPMS.
- Plegridy (peginterferon beta-1a): Given every two weeks by intramuscular or subcutaneous injection.
- Rebif (interferon beta-1a): Injected subcutaneously three times per week.
Oral DMTs
All oral DMTs are also approved to treat relapsing forms of MS, but not all therapies are approved for all three MS types. For example, Mavenclad is not recommended for CIS due to its safety profile.
- Aubagio (teriflunomide): Taken as once-daily tablets. Generic forms of this medication are available.
- Bafiertam (monomethyl fumarate): Taken twice daily as capsules.
- Gilenya (fingolimod): Taken once per day in the form of capsules, it is approved for children and adults ages 10 and older. Generic versions are also available.
- Mavenclad (cladribine): A short-course oral treatment taken as tablets. It is given in two treatment courses over two years. Each course consists of two treatment cycles, each lasting about four to five days and spaced roughly one month apart. Due to its safety profile, Mavenclad is generally recommended for patients who failed to respond to, or could not tolerate, other MS treatments. Generic versions are also available.
- Mayzent (siponimod): Taken as once-daily tablets.
- Ponvory (ponesimod): Taken once per day as tablets.
- Tascenso ODT (fingolimod): Taken once daily as oral disintegrating tablets. It is a bioequivalent formulation of Gilenya that’s also approved for children and adults ages 10 and older.
- Tecfidera (dimethyl fumarate): Taken as twice-daily capsules. Generic versions are available.
- Vumerity (diroximel fumarate): Taken as twice-daily capsules. Generic versions are also available.
- Zeposia (ozanimod): Taken as once-daily capsules.
DMTs administered by infusion
Infusion therapies are administered directly into the bloodstream, generally at a hospital or infusion center. These medications are all used to treat relapsing forms of MS, though their exact indications vary. Infusion schedules range from every few weeks to twice a year.
- Briumvi (ublituximab-xiiy): Given in hour-long infusions every six months.
- Lemtrada (alemtuzumab): Given as a once-daily infusion for five consecutive days during the first year, followed by a three-day course one year later. It is only approved for adults with RRMS and active SPMS and typically reserved for people who have had an inadequate response to at least two other therapies. Lemtrada is only available in the U.S. through a restricted distribution program.
- Mitoxantrone: Administered via infusion once every three months. It is approved for worsening relapsing MS and SPMS.
- Ocrevus (ocrelizumab): Given by infusion every six months. It is also approved for PPMS.
- Tysabri (natalizumab): Administered via hour-long infusions every four weeks. It is only available in the U.S. through a restricted distribution program. A biosimilar version is also available.
Strategies for selecting a DMT
Several factors influence the choice of which DMT to start or switch to, including disease activity, safety profile, tolerability, patient preference, and access. In general, when healthcare professionals treat a person with MS for the first time, they tend to follow one of two main strategies: escalation or induction.
The escalation strategy, which historically has been more common, involves starting with a moderately effective DMT that has a well-established safety profile. These “first-line” therapies are generally considered lower-risk options. If the disease continues to be active, the patient may then be switched to a “second-line” therapy that is more potent but may carry a higher risk of side effects.
Common first-line DMTs used in the escalation approach include:
- fumarates (Bafiertam, Tecfidera, Vumerity, and generics)
- glatiramer acetate (Copaxone and generics)
- interferon therapies, such as Avonex, Betaseron, Extavia, Plegridy, and Rebif
- teriflunomide (Aubagio and generics)
The induction strategy takes a more aggressive approach right from the start. It often involves starting treatment with a highly effective DMT — often one that was once considered a second-line therapy — to rapidly suppress disease activity and delay long-term disability progression. While these therapies are generally more potent, they can also pose greater risks and require closer monitoring.
High-efficacy DMTs that may be used in induction treatment include:
- anti-CD20 antibody therapies (Briumvi, Ocrevus, Ocrevus Zunovo, and Kesimpta)
- S1P receptor modulators (Gilenya, Mayzent, Zeposia, Ponvory, Tascenso ODT, and generics)
- Lemtrada
- Mavenclad and generics
- Tysabri and biosimilars
In recent years, early use of high-efficacy therapies has become increasingly recognized as the best strategy to delay long-term disability progression. Early and aggressive control of disease activity has been shown to have lasting benefits, and many neurologists around the world are now moving toward this treatment approach.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
