Disease-Modifying Therapies for Multiple Sclerosis

Treatment with a disease-modifying therapy (DMT) is crucial for most people with MS, since inflammation and progression typically continue even when no new symptoms are present. For this reason, most neurologists recommend starting a DMT as soon as possible if appropriate for that individual.

The Benefits of Taking a Disease-Modifying Therapy

• Disease-modifying therapies (DMTs) work to reduce the number and severity of symptom flare-ups, while also reducing the number of active lesions that appear on magnetic resonance imaging (MRI) scans.
• In addition, DMTs can delay and reduce the risk of progression of the disease and related disability.
• When individuals begin a treatment regimen early in their disease course, disease activity is slowed for most people with MS.



• Getting early treatment and staying on a DMT for MS may also delay and reduce the risk of conversion from relapsing-remitting MS (RRMS) to secondary-progressive MS (SPMS). This latter form of MS that follows RRMS exhibits a steady worsening, with or without relapses.
• Without treatment, about half of individuals with RRMS convert to SPMS within 10 years. However, since the introduction of the first DMT in 1993, those taking a DMT may experience either a reduced risk of conversion to SPMS or a delayed conversion to SPMS.

The Disease-Modifying Therapies and How They Work

MS is an autoimmune disease, where one’s immune system becomes misdirected and attacks the body’s myelin (the protective covering of the nerves) and eventually the axons (nerves of the central nervous system, or CNS). This misdirection of the immune system involves a cascade of events leading to the damage caused by MS, and each of the approved DMTs is designed to interfere in some way with this cascade of events – with the goal of slowing damage to the CNS.

To follow is an overview of how some of these DMTs work to slow MS disease activity, along with some of the corresponding medication names. These groupings are ordered according to when the first of each drug class became available, and the approval date is given for each medication.

Interferons

• Betaseron^® (interferon beta-1b) [1993]
• Avonex^® (interferon beta-1a) [1996]
• Rebif^® (interferon beta-1a) [2002]
• Plegridy^® (peginterferon beta-1a) [2014]

These are naturally occurring immune system proteins. They modulate the immune system by reducing the body’s immune response, and they also have antiviral properties. These are taken by self-injection.

Other immunomodulators

• Copaxone^® (glatiramer acetate) [1996] – This medication modifies immune processes that favor Th2 cells, which quiet inflammation and help block damaging T cells. It is taken by self-injection.
• Aubagio^® (teriflunomide) [2012] – This medication blocks an enzyme necessary for the growth of overactive immune cells. It is taken orally.

Sphingosine-1-phosphate (S1P) receptor modulators

• Gilenya^® (fingolimod, FTY720) [2010]
• Mayzent^® (siponimod) [2019]
• Zeposia^® (ozanimod) [2020]
• Ponvory^® (ponesimod) [2021]

These medications block potentially damaging immune-system cells (lymphocytes) from leaving lymph nodes, lowering their number in the blood and tissues. These medications are taken orally.

Dimethyl fumarate (DMF) medications

• Tecfidera^® (dimethyl fumarate) [2013]
• Vumerity^® (diroximel fumarate) [2019]
• Bafiertam^® (monomethyl fumarate) [2020]

This type of medication is absorbed in the gastrointestinal (GI) tract, where it’s converted and becomes the active agent monomethyl fumarate (MMF). DMF medications are selective immunosuppressants with neuroprotective and immunomodulatory effects. DMF medications are taken orally.

Monoclonal antibodies

• Tysabri^® (natalizumab) [2004]
• Lemtrada^® (alemtuzumab) [2014] (also considered a short-term immunosuppressant)
• Ocrevus^® (ocrelizumab) [2017]
• Kesimpta^® (ofatumumab) [2020]
• Briumvi^® (ublituximab-xiiy) [2022]
• Tyruko^® (natalizumab-sztn) [2023]
• Ocrevus Zunovo^® (ocrelizumab and hyaluronidase-ocsq) [2024]

These anti-inflammatory disease-modifying therapies deplete white blood cells called B cells. Four of these six are given via IV infusion, while one is taken by self-injection (Kesimpta) and one is given via injection by a medical professional (Ocrevus Zunovo).

Short-term immunosuppressants

• Novantrone^® (mitoxantrone) [2000] – This medication suppresses T cell, B cell, and macrophage activity thought to lead the attack on the myelin sheath. Novantrone^® is given via IV infusion. Please note that due to the potential for severe side effects, Novantrone is rarely, if ever, prescribed for individuals with MS.
• Mavenclad^® (cladribine) [2019] – This medication works by temporarily reducing the number of T and B cells (lymphocytes). Mavenclad selectively targets, depletes, and then reconstitutes immune system cells.

How Disease-Modifying Therapies Are Developed for MS

Beginning in the mid-1990s, nearly all of the disease-modifying therapies (DMTs) approved by the United States Food and Drug Administration (FDA) were only available for adults with relapsing-remitting MS (RRMS). This is the most common form of MS – initially experienced by 85% of those diagnosed with MS – and the easiest to observe for flare-ups and changes in symptoms.

When studying a potential medication to slow the disease process in RRMS, researchers can easily record the frequency and severity of relapses, as well as compare changes as seen on MRI. With the progressive forms of MS – secondary-progressive and primary-progressive – changes are more gradual and often don’t have the flare-ups experienced by those with RRMS, so measuring changes is less clear and requires far more time.

As studies in MS advanced, so has our understanding of the disease process and how the immune system affects different areas of the central nervous system (CNS). Several measures of disease progression have been developed to help assess changes in function, while improvements in MRI technology have enabled researchers to view lesions more closely to better determine ongoing disease activity.

Biomarkers also play an important role in evaluating disease activity, which not only helps to confirm a diagnosis and determine an optimal treatment plan, but also assists greatly with the study of experimental medications. A biomarker is something that can be measured to give us meaningful information about a patient’s health. In MS, this can include imaging or radiological findings, most notably on an MRI, as well as humoral biomarkers, with “humoral” referring to bodily fluids. Often relating to antibodies and immune responses, these include substances found in the blood or cerebrospinal fluid.

Due to these advancements in our understanding of MS as well as measures and technology, medications are now approved for both relapsing and progressive forms of MS in adults, and at least one DMT is also approved for pediatric MS. As noted earlier, we have also learned that early treatment means a greater reduction in risk of progression.

For those with clinically isolated syndrome (CIS) or radiologically isolated syndrome (RIS) – both of which are often precursors to an MS diagnosis – early treatment can delay or reduce the risk of being diagnosed with MS. While these are significant advances in the treatment of MS, research continues at a rigorous pace to find additional therapies aimed at treating all forms of MS.

In Conclusion

Treatments for MS have come a long way since the first disease-modifying therapy (DMT) was approved by the FDA in 1993. Options have gone from one to more than 20, with many more experimental medications in development for the treatment of MS. As research uncovers additional details on how MS affects the body, these experimental medications will provide different modes of action to slow disease activity in new and innovative ways.

Please visit MSAA’s Ultimate MS Treatment Guide for specific details on each of the disease-modifying therapies for MS.

Please note that MSAA does not endorse or recommend any specific drug or treatment. Individuals are advised to consult with a physician about the potential benefits and risks of the different treatment therapies.