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Relapsing-Remitting MS (RRMS) Treatments Explained

Updated on July 09, 2021
Medically reviewed by
Evelyn O. Berman, M.D.
Article written by
Kelly Crumrin

  • There are about 20 different disease-modifying therapies (DMTs) currently available to treat relapsing-remitting multiple sclerosis (RRMS).
  • Some DMTs may be taken orally, while others are injected or infused intravenously.
  • Your doctor may recommend a DMT based on factors including your disease activity, your risk for developing serious side effects, and which treatments you have tried before.
  • The only way to know whether a DMT will be effective is to begin taking it.

As of June 2021, there were 20 different disease-modifying therapies approved by the U.S. Food and Drug Administration (FDA) for treating multiple sclerosis (MS). Each DMT has been proven in multiple clinical trials to reduce the frequency of clinical attacks (also called relapses, flare-ups, or exacerbations) and the development of new lesions on the brain and spinal cord, which make up the central nervous system. Some DMTs have also been proven to slow the accumulation of disability.

Overall, DMTs slow disease progression and might help keep relapsing-remitting multiple sclerosis stable. Some DMTs have also been approved to treat other types of MS, such as secondary progressive MS and clinically isolated syndrome.

With so many treatment options, how can someone diagnosed with relapsing-remitting MS know which MS treatment will be best for them? For some people, how a DMT is taken and how often it is taken are important factors. Some prefer a medication taken orally over one taken by injection or intravenous infusion. Others prefer a more convenient dosage schedule with medication taken only a few times a year.

It can also help to know how doctors view which DMTs should be prescribed first and how different classes of DMTs work.

Evaluating the Risks and Benefits of DMTs

Treatments for relapsing-remitting MS, like all medications, have possible risks. Some side effects are more common, and others are extremely rare. Risk-averse people may prefer to avoid DMTs with a potential for serious side effects, even if those side effects occur very rarely. Others may prefer to focus on which DMT will be most effective in modifying the course of their RRMS, even if they carry a low risk for severe adverse effects. It is important to note that an individual’s risk for developing serious side effects is dependent on many factors. Your doctor can help you understand your risk for side effects with any medication.

Some DMTs have contraindications — circumstances that raise the risk for serious side effects in people with other health conditions in addition to MS. For instance, some DMTs are not recommended for people who test positive for John Cunningham virus — also known as JC virus — antibodies. Other DMTs may not be safe for people with liver dysfunction. If you have any other health problems or conditions, your doctor may avoid prescribing certain DMTs.

Doctors may recommend DMTs based on many factors. One important factor is RRMS disease activity. An individual’s RRMS may be active or inactive. Active disease is defined as having a clinical relapse or detecting new lesions on a magnetic resonance imaging (MRI) scan over a period of time, usually a year. Doctors may recommend different DMTs based on whether your RRMS is considered to be active or inactive.

What Are First-Line and Second-Line Treatments for RRMS?

According to the Consortium of Multiple Sclerosis Centers, a large membership organization of health care providers for those with MS, any approved DMT may be considered as an initial treatment for someone diagnosed with RRMS based on what is best for that individual.

Many doctors discuss DMTs for relapsing-remitting MS in terms of first-line and second-line treatments. First-line treatments are DMTs generally prescribed as an initial treatment for someone diagnosed with RRMS. Which treatments are considered first-line versus second-line is always evolving. In general, drugs with a higher risk for serious side effects are more likely to be considered as second- or third-line options.

FIRST-LINE DMTs FOR RELAPSING-REMITTING MS
Disease-modifying treatment Method of administration Dosage schedule
Aubagio (teriflunomide) Oral Once a day
Avonex (interferon beta-1a) Injection Once a week
Bafiertam (monomethyl fumarate) Oral Twice a day
Betaseron (interferon beta-1b) Injection Every other day
Copaxone (glatiramer acetate) Injection Daily or three times a week
Extavia (interferon beta-1b) Injection Every other day
Glatopa (glatiramer acetate) Injection Daily or three times a week
Glatiramer acetate Injection Daily or three times a week
Kesimpta (ofatumumab) Injection Monthly
Ocrevus (ocrelizumab) IV infusion Every six months
Plegridy (peginterferon beta-1a) Injection Every two weeks
Rebif (interferon beta-1a) Injection Three times a week
Tecfidera (dimethyl fumarate) Oral Twice a day
Vumerity (diroximel fumarate)* Oral Twice a day

Based on information sourced from “Treatment for MS” provided by MS Focus at https://msfocus.org/Get-Educated/Treatment-for-MS.aspx

*Based on information sourced from “Disease Modifying Therapies for MS” provided by the National Multiple Sclerosis Society at https://nationalmssociety.org/DMT

Second-line or even third-line treatments may be recommended if it becomes evident that the current treatment is failing. Treatment failure can mean different things for different people with RRMS. It’s important to remember that no DMT can cure or completely stop multiple sclerosis.

According to the Consortium of Multiple Sclerosis Centers, switching treatments may be considered when:

  • Your RRMS is not responding adequately to treatment. This is a subjective measurement, but signs may include a relapse, new or worsening lesions, or worsening results during a neurologic exam within a year of starting therapy.
  • You have significant side effects on the first therapy, or a new health concern or contraindication raises the risk for side effects.
  • You no longer have access to the first DMT.
  • You have trouble taking the first DMT or cannot tolerate its side effects.
SECOND-LINE DMTs FOR RELAPSING-REMITTING MS
Disease-modifying treatment Method of administration Dosage schedule
Gilenya (fingolimod) Oral Once a day
Lemtrada (alemtuzumab) IV infusion Five days in a row, then three days 12 months later
Mavenclad (cladribine) Oral 10 pills in the first year, 10 pills in the second year
Mayzent (siponimod) Oral Once a day
Novantrone (mitoxantrone) IV infusion Every three months
Ponvory (ponesimod) Oral *Once a day
Tysabri (natalizumab) IV infusion Every four weeks
Zeposia (ozanimod) Oral Once a day

Based on information sourced from “Treatment for MS” provided by MS Focus at https://msfocus.org/Get-Educated/Treatment-for-MS.aspx

*Based on information sourced from “Ponvory Highlights of Prescribing Information” at www.janssenlabels.com/package-insert/product-monograph/prescribing-information/PONVORY-pi.pdf

†Based on information sourced from “Zeposia Highlights of Prescribing Information” at https://packageinserts.bms.com/pi/pi_zeposia.pdf

How Does Each Class of Medications for RRMS Work?

Among the DMTs approved for treating RRMS, there are several mechanisms of action – in other words, different ways of working. Most DMTs modify different aspects of the immune system to prevent autoimmune attacks on the myelin that sheathes nerve fibers. Understanding how disease-modifying therapies work can provide insight into why your doctor recommends a medication. For instance, if you are switching drugs because the DMT you have been taking has been ineffective, your doctor will likely recommend a drug with a different mechanism of action.

HOW DIFFERENT DMTs WORK IN RELAPSING-REMITTING MS
Disease-modifying treatments Believed mechanism of action
Betaseron (interferon beta-1b)
Extavia (interferon beta-1b)
Beta interferons inhibit T cell numbers and activation. They encourage the activity of regulatory T cells and the death of T cells involved in autoimmunity. They help prevent the migration of white blood cells across the blood-brain barrier.

Avonex (interferon beta-1a)

Rebif (interferon beta-1a)

Plegridy (peginterferon beta-1a)

These work similarly to interferon beta-1b, above.

Copaxone (glatiramer acetate)

Glatiramer acetate

Glatopa (glatiramer acetate)

Glatiramer acetate encourages and activates helper T cells and regulatory T cells. It supports the growth and development of neurons (brain cells). It may also target antigen-presenting cells involved in autoimmune attacks.

Gilenya (fingolimod)*

Mayzent (siponimod)

Ponvory (ponesimod)
Zeposia (ozanimod)

These drugs block white blood cells from leaving lymph nodes, reducing their numbers in the central nervous system.
Aubagio (teriflunomide) Teriflunomide reduces the number of activated white blood cells in the central nervous system.

Bafiertam (monomethyl fumarate)§

Tecfidera (dimethyl fumarate)

Vumerity (diroximel fumarate)**

These reduce inflammation involved in MS.
Tysabri (natalizumab) Natalizumab prevents white blood cells from migrating into inflamed tissues.
Mavenclad (cladribine) Cladribine reduces the number of white blood cells, especially B cells.
Lemtrada (alemtuzumab) Alemtuzumab lowers the number of circulating B cells and T cells.

Ocrevus (ocrelizumab)

Kesimpta (ofatumumab)

These encourage the destruction of B cells involved in MS attacks.

Based on information sourced from “CMSC Practical Guidelines for the Selection of Disease-Modifying Therapies in Multiple Sclerosis” at https://cmscscholar.org/cmsc-practical-guidelines-for-the-selection-of-disease-modifying-therapies-in-ms/

*Based on information sourced from “FDA Approves Oral Vumerity (Diroximel Fumarate), Similar to Tecfidera, for Relapsing MS” provided by the National Multiple Sclerosis Society at www.nationalmssociety.org/About-the-Society/News/FDA-Approves-Oral-Vumerity™-(Diroximel-Fumarate)

§Based on information sourced from Bafiertam at www.bafiertam.com

**Based on information sourced from “Sphingosine-1 Phosphate Receptor Modulators in the Treatment of Multiple Sclerosis” provided by U.S. Pharmacist at www.uspharmacist.com/article/sphingosine1-phosphate-receptor-modulators-in-the-treatment-of-multiple-sclerosis#

†Based on information sourced from “The Story of Cladribine Reaches Its Climax” provided by Nature at www.nature.com/articles/d42859-018-00029-1

For people living with active RRMS, the only way to know whether a disease-modifying treatment will be effective is to begin taking it. Many people with RRMS find it necessary to switch to a different DMT over the course of their treatment.

Talk With Others Who Understand

On MyMSTeam, the social network for people with multiple sclerosis and their loved ones, more than 170,000 members come together to ask questions, give advice, and share their stories with those who understand life with MS.

Do you still have questions about disease-modifying treatments for MS? Share them in the comments below, or start a conversation with others on MyMSTeam.

All updates must be accompanied by text or a picture.
Evelyn O. Berman, M.D. is a neurology and pediatric specialist and treats disorders of the brain in children. Review provided by VeriMed Healthcare Network. Learn more about her here.
Kelly Crumrin is a senior editor at MyHealthTeam and leads the creation of content that educates and empowers people with chronic illnesses. Learn more about her here.

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