What Is the First Line of Treatment for Multiple Sclerosis?

In multiple sclerosis (MS), the immune system attacks the protective covering (myelin) of nerve fibers within the brain and spinal cord. This damages the nerves and may lead to a variety of symptoms, including numbness, vision problems, muscle weakness, and walking difficulties.

Disease-modifying therapies (DMTs) are usually the first-line treatment for MS. These medications decrease the number and severity of immune system attacks and slow the natural progression of the disease.

There are multiple DMTs available, and they can be taken in different ways—by mouth, as a shot, or through an intravenous (IV) line in your vein. Since there is no standard guideline or algorithm for starting one DMT over another, selecting a drug when diagnosed with MS can be a challenging task.

This article reviews how people with MS and their healthcare team go about choosing a DMT. It also discusses how a person's response to that drug is carefully monitored.

Doctor discusses treatment with woman with multiple sclerosis

Deepak Sethi / Getty Images

Initial Treatment for MS

Most people with MS are initially diagnosed with relapsing-remitting MS (RRMS). With RRMS, patients experience relapses followed by periods of recovery, called remission.

What Is a Relapse?

A relapse, or flare-up, occurs when a person develops new neurologic symptoms or their old MS symptoms worsen. Symptoms may last days to months before they go away or improve.

In addition to RRMS, most DMTs are approved by the Food and Drug Administration (FDA) to treat the following types of MS:

When choosing among the DMT options, neurologists (specialists in conditions affecting the nervous system) and the people they treat consider several factors like the drug's safety profile, level of effectiveness, cost, and route of administration.

How active the person's disease is and their preference and lifestyle factors (e.g., desire for pregnancy or breastfeeding) are also considered.

After careful thought and discussion, one of the following three treatment approaches is generally followed:

  • Starting a highly effective DMT
  • Starting a low-risk DMT
  • Starting an oral DMT

Highly Effective DMTs

Research suggests that monoclonal antibodies are highly effective in reducing the number of MS relapses a person may experience.

Monoclonal antibodies work by targeting specific cells or markers within the immune system. They are generally selected for patients who experience frequent relapses and magnetic resonance imaging (MRI) lesions (areas of inflammation).

The following monoclonal antibodies may be prescribed as first-line treatments for MS:

Primary Progressive MS

Ocrevus is the first DMT to ever be approved for primary progressive MS (PPMS). This form of MS is characterized by slowly worsening symptoms and disability from the start of the disease. Relapses may occasionally occur later on in the disease, but not early on.

While monoclonal antibodies may offer you the best chances of keeping your MS at bay, they carry an increased risk of more worrisome side effects, including serious infections or cancer.

For example, Tysabri increases your risk of developing a rare but potentially fatal brain infection called progressive multifocal leukoencephalopathy (PML). PML is caused by the reactivation of the John Cunningham (JC) virus.

Since your risk of developing PML increases if you are positive for antibodies against the JC virus (indicating a prior infection), your neurologist will order a blood test to check you for anti-JCV antibodies before starting the drug and every six months afterward.

Positive anti-JCV antibodies may warrant discontinuation of the drug.

Likewise, with Ocrevus, there is an increased risk of serious skin infections and cancer, including breast cancer. There is also a reported case of PML in a 78-year-old man with progressive MS treated with Ocrevus.

Lastly, another possible downside of monoclonal antibodies is that some people may not want to undergo infusions or injections, perhaps because of inconvenience or a fear of needles.

Low-Risk DMTs

DMTs considered of low risk in causing serious side effects include Copaxone and Glatopa (glatiramer acetate) and the beta interferon drugs (e.g., Avonex, Rebif, Betaseron, Extavia, and Plegridy).

Copaxone and Glatopa are injected subcutaneously either every day or every three days (a higher dose is used). 

Beta interferon drugs are administered in the following manner:

  • Avonex is injected intramuscularly (into a muscle) once a week.
  • Betaseron and Extavia are injected subcutaneously every other day.
  • Rebif is injected subcutaneously three times a week.
  • Plegridy is injected subcutaneously or intramuscularly every 14 days.

While these injectable DMTs have a long-term history of being safe, research suggests they may not be as effective in reducing relapses.

The injectable DMTs also require that you (or a loved one) give yourself a shot. This may be a problem for some people.

Oral DMTs

Oral DMTs are usually preferred by people with MS who cannot tolerate injectable or infused DMTs. They are generally considered intermediate in terms of safety and effectiveness.

Oral DMTs include:

  • Tecfidera (dimethyl fumarate), Vumerity (diroximel fumarate), and Bafiertam (monomethyl fumarate) are chemically similar pills taken twice daily. They are believed to have antioxidant properties and alter the immune system in such a way that protects nerve cells from damage.
  • Gilyena (fingolimod), Mayzent (siponimod), and Zeposia (ozanimod) are similar drugs taken once a day. They work by trapping certain white blood cells in your lymph nodes, preventing them from launching attacks within your brain and spinal cord.
  • Aubagio (teriflunomide) is taken once daily and works by blocking the action of certain immune system cells involved in MS.

Pediatric MS

Gilenya is the first and only FDA-approved medication to treat children and adolescents age 10 years and older with MS.

How to Tell If Treatment Is Working

After starting a DMT, you will see your neurologist every three to six months or so to ensure that your medication is working well and safely for you.

During your appointments, your neurologist will monitor you for new relapses by performing a neurological examination and asking you about any new or worsening symptoms like fatigue, pain, or problems with balance or walking.

They may also evaluate whether your disease has progressed by asking you questions using a tool called the Expanded Disability Status Scale (EDSS).

Periodic MRIs are also performed to see if you are developing new lesions, regardless of whether or not you are having symptoms.

When to Talk to Your Neurologist

Contact your neurologist if you are experiencing new or recurring neurological symptoms for at least 24 hours. You may be having a relapse or a pseudo-relapse (temporary worsening of symptoms caused by external factors, like heat or infection).


Pseudo-relapses are "false" relapses (not caused by an increase in disease activity) and are harmless. Symptoms go away shortly after the external factor is removed (e.g., you cool down if overheated).

If you are experiencing relapses on your new DMT, your neurologist may consider switching you to a different DMT.

Be sure to also talk to your neurologist if you are experiencing bothersome side effects, or if you are experiencing a lifestyle change that may affect how you care for your MS—for example, pregnancy or a change in your insurance.

Seek medical attention right away by calling your healthcare provider or going to your nearest emergency room if your symptoms are severe and/or debilitating (e.g., severe weakness or loss of balance).

Other Treatment Options for MS

While DMTs are the mainstay of treatment for MS, a type of bone marrow transplant called autologous hematopoietic stem cell transplantation (aHSCT) may be a reasonable option for people whose disease continues to be very aggressive despite the use of DMTs.

With aHSCT, a person’s immune system is "reset" using hematopoietic (blood-forming) stem cells taken from their own body. With a new, healthy immune system, the attacks on myelin and nerve fibers will theoretically be thwarted.

Experimental MS therapies are also being explored that help repair damaged myelin within the brain and spinal cord.

One such therapy is a mesenchymal stem cell transplant. With this transplant, stem cells are isolated from a person's fat, skin, or bone marrow, multiplied and altered within a laboratory, and then administered back into the body.


There are no formal treatment guidelines to follow for selecting an MS disease-modifying therapy (DMT). Instead, you and your neurologist will consider multiple factors, including how active your disease is, and the individual drug's safety profile and level of effectiveness.

After choosing and starting a DMT, your MS care team will monitor you closely for side effects. They will also keep track of your symptoms and ask you to undergo periodic MRIs in order to see how well the drug is working.

A Word From Verywell

Whether you are newly diagnosed or switching medications, starting a new DMT is no easy task. The best thing you can do is educate yourself about your options and be open and honest with your MS healthcare provider about your concerns.

You may also consider connecting with others who have taken the DMT you are starting on. Joining an MS support group like MS World or MSFriends is a good place to start.

Frequently Asked Questions

  • Does early treatment of MS help?

    Yes. Treating MS as early as possible is associated with better outcomes for patients.

  • When should you start treatment for MS?

    Treatment for MS should be started as soon as possible after diagnosis. This is because the earlier you start a disease-modifying therapy (DMT), the better chance you have of slowing your disease progression and reducing the number of relapses you have.

  • What is the second line of treatment for multiple sclerosis?

    Second-line treatments for MS are given when the initially selected DMT cannot be tolerated or is not effective. For example, if a person's disease progresses on an interferon drug, they may be switched to an oral or infused drug, such as Gilenya (fingolimod) or Ocrevus (ocrelizumab), respectively.

    Sometimes DMTs are considered second-line treatments because of safety concerns. This is the case with Mavenclad (cladribine) and Lemtrada (alemtuzumab).

12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Kalincik T, Diouf I, Sharmin S et al. Effect of disease-modifying therapy on disability in relapsing-remitting multiple sclerosis over 15 years. Neurology 2021;96(5):e783-e797. doi:10.1212/WNL.0000000000011242

  2. Rae-Grant A, Day GS, Marrie RA et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90(17):777-788. doi:10.1212/WNL.0000000000005347

  3. Olek MJ, Mowry E. (2022). Initial disease-modifying therapy for relapsing-remitting multiple sclerosis in adults. González-Scarano F, ed. UpToDate. Waltham, MA: UpToDate.

  4. Kalincik T, Brown JWL, Robertson N et al. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study. Lancet Neurol. 2017;16(4):271-281. doi:10.1016/S1474-4422(17)30007-8

  5. Mancinelli CR, De Rossi N, Capra R et al. Ocrelizumab for the treatment of multiple sclerosis: safety, efficacy, and pharmacology. Ther Clin Risk Manag. 2021;17:765–776. doi:10.2147/TCRM.S282390

  6. Patel A, Sul J, Gordon ML. Progressive Multifocal Leukoencephalopathy in a Patient With Progressive Multiple Sclerosis Treated With Ocrelizumab Monotherapy. JAMA Neurol. 2021 Jun; 78(6): 1–6. doi:10.1001/jamaneurol.2021.0627

  7. Fogarty E, Schmitz S, Tubridy N, Walsh C, Barry M. Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: Systematic review and network meta-analysis. Mult Scler Relat Disord. 2016;9:23-30. doi:10.1016/j.msard.2016.06.001

  8. Faissner S, Gold R. Oral therapies for multiple sclerosis. Cold Spring Harb Perspect Med. 2019;9(1):a032011. doi:10.1101/cshperspect.a032011

  9. Food and Drug Administration. FDA expands approval of Gilenya to treat multiple sclerosis in pediatric patients.

  10. Sormani MP, Muraro PA, Schiavetti I, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a meta-analysisNeurology. 2017;88(22):2115-2122. doi:10.1212/WNL.0000000000003987

  11. Bejargafshe MJ, Hedayati M, Zahabiasli S, Tahmasbpour E, Rahmanzadeh S, Nejad-Moghaddam A. Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosisStem Cell Investig. 2019;6:44. doi:10.21037/sci.2019.10.06

  12. Kavaliunas A, Manouchehrinia A, Stawiarz L. Importance of early treatment initiation in the clinical course of multiple sclerosis. Mult Scler. 2017;23(9):1233-1240. doi:10.1177/1352458516675039

By Colleen Doherty, MD
 Colleen Doherty, MD, is a board-certified internist living with multiple sclerosis.