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Disease Modifying Agents

Since the first FDA approved medication became available in 1993, a total of seven medications have been FDA approved for use in multiple sclerosis (MS).

There are 10 medications approved by the FDA for use in multiple sclerosis (MS). Each of these medications in some way changes the way MS develops. In general, the medications reduce the number of times MS gets worse, reduce the amount of activity seen on MRI scanning, and may slow the advancement of MS.

There are five medications that are injectable agents (given by a needle). These are often used as the first medicine in patients with the relapsing form of multiple sclerosis:

  • Interferon beta-1a intramuscular (in the muscle) injection once a week (Avonex®)
  • Interferon beta-1b subcutaneous (under the skin) injection every other day (Betaseron®)
  • Interferon beta-1a subcutaneous injection three days a week (Rebif®)
  • Interferon beta-1b subcutaneous injection every other day (Extavia®)
  • Glatiramer acetate subcutaneous injection every day (Copaxone®)

Each of these medications has its own side effects and risks. All have information materials provided by the manufacturers to provide patient education. In addition, the National Multiple Sclerosis Society ( provides information on all of these medications.

In general, one of these five medications may be used as the first medication for MS. In large research trials in patients with relapsing MS, each of these medications was about equal in reducing the number of MS attacks. In addition, all showed a reduction in new lesions forming in the brain (as seen on MRI), as well as fewer new enhancing lesions (areas where gadolinium dye was seen in the brain to show a new area of MS).

All of these medicines require certain paperwork and must be preapproved by insurance. Many of them are supported by an assistance program if the patient has trouble paying for the medicine.

The interferons (Avonex, Betaseron, Rebif, Extavia) are biological agents that change the way the immune system works, without reducing the body’s ability to fight off infection. The interferons frequently cause flu-like symptoms (fever, chills, muscle aches, fatigue) after each injection. It’s possible to lessen these symptoms by taking acetaminophen or ibuprofen. These symptoms generally become less of a problem over time.

Patients who take interferon medications need to have blood work every three to six months to make sure that their liver function and blood counts do not change significantly. Interferon-beta-1b may rarely cause a breakdown of the skin at the part of the body where it is injected. If this occurs, the medication has to be stopped.

A healthcare provider will teach the patient and family how to inject these medicines safely. All of these medications have been used in thousands of patients and have a good safety record. These medicines can be used safely for years, depending on the side effects and whether they are controlling the MS.

A follow-up MRI may be useful to make sure that there are reductions in both new lesions and enhancing lesions. This would show that the medicine is working biologically.

Rare side effects of the interferons include immune inflammation (swelling) of the liver, a change in how the kidney functions, and, sometimes, an increase in symptoms of depression.

Glatiramer acetate (Copaxone) reduces the number of relapses of MS compared with placebo (sugar pill) and reduces MRI activity in treated patients. Side effects of glatiramer acetate include reactions (swelling, redness, itching and, sometimes, dimpling of the skin) at the spot of the injection. In addition, patients occasionally feel chest tightness and shortness of breath known as an “idiosyncratic reaction.” This appears to be a safe event and is not a cardiac (heart) or allergic reaction.

Otherwise, glatiramer acetate has a safe record and does not need to be monitored. Just as with the interferons, neurologists tend to repeat the MRI to make sure that there is less new disease activity than in the past.

Recently, neurologists have begun to define “breakthrough disease” when people are on one of these medicines. Currently, it is thought of as:

  • Formation of a major new lesion or enhancing lesion as seen on MRI after the medicine has had a chance to work (that is, not right after starting medicine)
  • One relapse in a year with significant functional problems (that is, problems with vision, walking change, double vision, hand function, etc.)
  • Two or more relapses in a year while on medicines

We know that some patients with MS will develop progressive changes, which seem to be different than relapses. Relapses are new or different neurological symptoms that take place over days or weeks and are not caused by infection or fever. Progression is a gradual worsening over months or years, rather than days or weeks.

When the injectable medicines have been tested in progressive patients who do not have relapses, they do not seem to affect the course of the progression in a significant way. We therefore use these medicines mostly in patients with relapsing symptoms, even if there is also some progression.

Specific information for each medicine can be found at the following websites:

  • Interferon beta-1a intramuscular (in the muscle) injection once a week (Avonex®,
  • Interferon beta-1b subcutaneous (under the skin) injection every other day Betaseron®,
  • Interferon beta-1a subcutaneous injection three days a week (Rebif®,
  • Interferon beta-1b subcutaneous injection every other day (Extavia®,
  • Glatiramer acetate subcutaneous injection every day (Copaxone®,

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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 3/8/2016...#9065

Dimethyl fumarate (also called Tecfidera, or BG-12) is an oral MS therapy approved in March 2013 for treatment of relapsing forms of MS.

Dimethyl fumarate was evaluated in two large, two-year clinical trials and found to decrease the frequency of clinical relapses, reduce new lesions on MRI, and (in one study) slow the progression of disability. The main side-effects of dimethyl fumarate are skin flushing (redness, warmth, and sometimes itching) and gastrointestinal symptoms (nausea, vomiting, abdominal pain, and diarrhea). Typically, the gastrointestinal symptoms improve within a month of treatment. Dimethyl fumarate has not be evaluated in either secondary progressive MS or primary progressive MS, so is generally not recommended in those patients without evidence for active inflammation.

Who should use this new treatment?

Mellen Center for Multiple Sclerosis physicians feel that dimethyl fumarate can be an appropriate treatment option for first-line treatment of relapsing forms of MS and an alternative treatment to other MS therapies. In general, patients who are stable on their current MS therapy, who tolerate it well, and don’t have significant risks of complications will be recommended to continue that treatment and not change to dimethyl fumarate. Current MS Patients at the Mellen Center who are interested in exploring whether dimethyl fumarate may be appropriate to them should contact their clinical team for further guidance. In most cases, they will need a clinical visit to the center to discuss the therapy, its risks and benefits, and whether it might be appropriate for an individual patient. Please view the video on this page for further information.

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