Riteesha G. Reddy, MD, is a board-certified rheumatologist and internist at a private practice in Dallas, Texas.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects nearly 1 million people in the United States. There is no cure for MS, but disease-modifying therapies (DMTs) can delay disability and slow the condition's progression.

The Food and Drug Administration (FDA) approved several new DMTs to treat MS in the last few years. The emergence of these drugs has been a remarkable step in changing the outlook on living with MS. It has also provided patients with multiple options for treating their disease.

This article will review these newer DMTs, including how they work, their common side effects and contraindications, and their dosing schedule.

Multiple sclerosis (MS) occurs when a person's immune system attacks and damages the protective myelin covering surrounding nerve fibers within the central nervous system (CNS). The CNS is composed of your brain, spinal cord, and the optic nerves of your eyes.

DMTs are medications that help prevent the immune system from launching these attacks and damaging myelin. Most MS DMTs are approved to treat relapsing MS.

Relapsing MS includes the following MS types:

By reducing the number and severity of relapses and slowing the natural progression of your disease, DMTs serve as an essential first step in treating MS.

Sphingosine 1-phosphate receptor (S1PR) modulators are MS DMTs that work by trapping immune system cells in the lymph nodes, preventing them from entering the central nervous system and causing damage.

Gilenya (fingolimod) was the first sphingosine 1-phosphate receptor modulator to be approved for MS.

Three more SP1R modulators were approved to treat relapsing forms of MS in adults. These drugs are all taken by mouth once daily and include:

Common side effects of all three above drugs include elevation of liver enzymes (seen on a blood test) and high blood pressure.

Upper respiratory tract infections may also occur when taking Ponvory, and headaches may occur when taking Mayzent.

Additional common side effects of Zeposia include:

Possible serious side effects of all three S1PR modulators include:

Due to potential side effects, your MS healthcare provider will require that you undergo an eye evaluation, electrocardiogram (ECG), and various blood tests, including a complete blood count and liver function panel, prior to starting Ponvory, Mayzent, or Zeposia,

Ponvory, Mayzent, and Zeposia are all contraindicated (advised against) in people with the following conditions:

Mayzent is also contraindicated in people who have a specific genotype (genetic variation) called CYP2C9*3/*3. This genotype increases the blood levels of Mayzent.

Zeposia is additionally contraindicated in people with severe, untreated sleep apnea (in which breathing stops and starts repeatedly during sleep) and people who are taking a type of drug called a monoamine oxidase inhibitor.

Mavenclad (cladribine)  is an oral medication taken in two annual treatment courses. Each yearly treatment course consists of two cycles (lasting four or five days) separated by about four weeks.

Mavenclad was approved in 2019 to treat relapsing-remitting MS and active secondary progressive disease in adults.

Mavenclad works by temporarily lowering the number of T and B lymphocytes in your body. T and B lymphocytes are white blood cells that normally work to protect your body against infection and disease. 

Due to this lowering of infection-fighting cells, a blood test that measures your lymphocyte counts must be performed before, during, and after treatment with Mavenclad.

The most common side effects of Mavenclad are upper respiratory tract infections, headache, and low white blood cell counts.

There is also an increased risk of life-threatening infections, including tuberculosis (TB, a bacterial infection of the lungs), hepatitis B or C (conditions causing inflammation of the liver), shingles (viral infection causing a painful rash), and a rare brain infection called progressive multifocal leukoencephalopathy (PML). Mavenclad has also been linked to an increased risk of cancer.

While a highly effective drug, due to its safety profile, Mavenclad is typically only recommended for people who cannot tolerate or who do not respond to other DMTs.

Mavenclad is contraindicated in patients with the following conditions:

Mavenclad is also contraindicated in people of any sex who have reproductive potential and who do not plan to use effective contraception during Mavenclad treatment and for six months after the last dose in each treatment course. 

Vumerity (diroximel fumarate) is a capsule taken twice daily by mouth and was approved in 2019 for relapsing MS in adults.

Vumerity is in the same class of drugs as Tecfidera (dimethyl fumarate), a DMT approved by the FDA in 2013, but has been found to be better tolerated, especially when it comes to gastrointestinal side effects. It's believed to work through various anti-inflammatory and antioxidant properties.

The most common side effects of Vumerity are:

Vumerity is contraindicated in those with a known hypersensitivity to diroximel fumarate or dimethyl fumarate, and to patients already taking Tecfidera.

Bafiertam (monomethyl fumarate) is similar to Vumerity and Tecfidera, but it has a different chemical structure. It was approved in 2020 to treat relapsing MS and is taken by mouth twice daily.

The most common side effects of Bafiertam are:

Bafiertam is contraindicated in those with a known hypersensitivity to monomethyl fumarate, diroximel fumarate, or dimethyl fumarate, and to patients already taking Vumerity or Tecfidera.

Ocrevus (ocrelizumab) is an infused medication (delivered into a vein) taken once every six months. It was approved in 2017 to treat relapsing forms of MS and primary progressive MS (PPMS)  in adults.

Primary progressive MS is a type of MS characterized by gradually worsening symptoms and disability over time, in the absence of discrete relapses.

Ocrevus is a monoclonal antibody that targets and destroys B cells that have a CD20 receptor, which is a type of marker located on their surface. When Ocrevus binds to CD20, the B cells are destroyed and removed from the body.

Ocrevus is considered highly effective in reducing MS relapses, and as such, appears to be a promising drug in the treatment of people with aggressive disease. That said, long-term data regarding its benefit and safety still needs to be performed.

The most common side effects of Ocrevus are:

Serious infections, including PML and those caused by the herpes simplex virus (herpes) and varicella-zoster virus (shingles), have been reported with Ocrevus. There may also be an increased risk of cancer, including breast cancer.

Ocrevus is contraindicated in those with an active hepatitis B viral infection and those with a history of a life-threatening infusion reaction to the drug.

The approval of several new MS disease-modifying therapies (DMTs) since 2016 has not only improved lives but has also provided hope that a cure for MS is on the horizon. The vast majority of these medications are approved to treat relapsing forms of MS.

They work to slow the disease down and have varying levels of effectiveness and safety profiles. DMTs also come in different forms that may be taken orally, injected, or infused.

If you have been recently diagnosed with MS and are starting a DMT (or you are thinking about changing DMTs), it's important to carefully consider the drug's level of effectiveness, potential side effects, and route of administration. You will also want to think about how the drug may affect various lifestyle choices, like family planning.

While it's sensible to reach out to others about their experience with a particular DMT, remember that what works well for someone else may not be the right medication choice for you.

There is no single best drug for treating MS. MS disease-modifying therapies (DMTs) vary widely in their level of effectiveness and safety profile. For example, the infused monoclonal antibody drugs Tysabri (natalizumab) and Ocrevus (ocrelizumab) are considered highly effective in reducing MS relapses. However, compared to older MS DMTs, they are associated with an increased risk of serious infections.

While more research is needed, it appears that Mavenclad and Ocrevus have similar levels of effectiveness when it comes to reducing MS relapses.

One MS DMT Tecfidera (dimethyl fumarate) is associated with stomach problems, including nausea, vomiting, diarrhea, pain, and indigestion. The good news is that a similar drug Vumerity (diroximel fumarate) tends to be better tolerated, especially when it comes to stomach-related side effects.

National MS Society. MS prevalence.

Dargahi N, Katsara M, Tselios T, et al. Multiple sclerosis: immunopathology and treatment update. Brain Sci. 2017;7(12):78. doi:10.3390/brainsci7070078

Food and Drug Administration. Highlights of prescribing information (Ponvory).

Food and Drug Administration. Highlights of prescribing information (Mayzent).

Food and Drug Administration. Highlights of prescribing information (Zeposia).

Food and Drug Administration. Highlights of prescribing information (Mavenclad).

Food and Drug Administration. Highlights of prescribing information (Vumerity).

Food and Drug Administration. Highlights of prescribing information (Bafiertam)

Food and Drug Administration. Highlights of prescribing information (Ocrevus).

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Berardi A, Siddiqui MK, Treharne C, Harty G, Wong SL. Estimating the comparative efficacy of cladribine tablets versus alternative disease modifying treatments in active relapsing-remitting multiple sclerosis: adjusting for patient characteristics using meta-regression and matching-adjusted indirect treatment comparison approaches. Curr Med Res Opin. 2019;35(8):1371-1378. doi:10.1080/03007995.2019.1585779

Naismith RT, Wundes A, Ziemssen T et al. Diroximel fumarate demonstrates an improved gastrointestinal tolerability profile compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: results from the randomized, double-blind, phase III EVOLVE-MS-2 study. CNS Drugs. 2020;34(2):185-196. doi:10.1007/s40263-020-00700-0

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