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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).

Since the first FDA approved medication became available in 1993, a total of 10 medications have been approved by the FDA for use in multiple sclerosis (MS). Each of these medications in some way alters the course of MS. In general, the medications reduce the frequency of exacerbations of MS, reduce the amount of activity seen on MRI scanning, and may slow progression of MS.

There are 5 medications which are commonly used as a first line medicine in patients with relapsing form of multiple sclerosis which are injectable agents. These include:

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

Each of these medications has its own side effects and risks. All of the approved medications have information materials provided by the manufacturers to guide 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 a first choice medication for MS. In large research trials in patients with relapsing MS, each of these medications showed a similar reduction of attack frequency which was the primary measure of effect in these trials. In addition, all showed a reduction in new lesions forming in the brain on MRI imaging, as well as fewer new enhancing lesions (areas where gadolinium dye was seen in the brain indicating a new area of MS). Each differs in the frequency and route of administration, as well as in the side effect profile.

All of these medicines require specific paperwork. All require preapproval by insurance, and many of them are supported by an assistance program when there is a financial burden of the medicine use.

The interferons are biological agents which alter immune function, decreasing some of the more active inflammatory processes in the system, thus decreasing the kind of immune activity seen in MS without suppressing the body’s ability to fight off infection. The interferons (Avonex, Betaseron, Rebif, Extavia) frequently cause flu-like symptoms (fever, chills, muscle aches, fatigue) after each injection. This side effect may be pretreated with medications such as acetaminophen or ibuprofen, and in general tends to become less over time. The interferon medications require monitoring of blood work every 3 to 6 months to ensure that liver function and blood counts do not change significantly. Interferon-beta-1b may rarely cause a breakdown of the skin at the injection site which requires the medication to be stopped.

All of these medications have been used in thousands of patients over years and have a good safety record. Rare side effects of the interferons include immune inflammation of the liver, altered kidney function, and occasionally an increase in symptoms of depression. Teaching is usually provided to help patients and families understand how to inject these medicines safely. A follow-up MRI may be useful to ensure that there is a reduction in new lesion formation and a reduction in enhancing lesions, indicating that the medicine is working biologically. These medicines can be used safely for years, depending on the side effect profile and whether they are achieving enough control of the MS disease activity.

Glatiramer acetate (Copaxone) is a substance made of chains of amino acids that resemble the myelin structure. It is thought that this medicine acts as a ‘decoy,’ altering the immune attack on the body’s naturally occurring myelin. Glatiramer acetate also reduces the number of relapses of MS compared with placebo and reduces MRI activity in treated patients. Glatiramer acetate (Copaxone) tends to give injection site reactions such as swelling, redness, itching and, occasionally, an atrophy of the tissues under the skin at the injection site causing indentation of the skin. In addition, patients occasionally experience a reaction where they feel chest tightness and shortness of breath known as an ‘idiosyncratic reaction.’ This appears to be a safe event and is not a cardiac or allergic reaction. Otherwise, glatiramer acetate has a well-defined long term safety record. No specific monitoring of this medicine is required. Just as with the interferons, over time neurologists tend to repeat the MRI to ensure that there is less new disease activity than in the past.

Recently, neurologists have begun to define what constitutes ‘breakthrough disease’ when people are on one of these medicines. At present, this is usually thought of as:

Significant new lesion or enhancing lesion formation on follow-up MRI scanning done at a time when 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 like visual change, 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 appear to be different from relapses. Relapses are new or different neurological symptoms occurring over days or weeks not due to 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 primarily 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 weekly (Avonex) intramus¬cular (in the muscle) injection
  • Interferon beta-1b every other day (Betaseron) subcutaneous (under the skin) injection
  • Interferon beta-1a three days a week (Rebif) subcutaneous injection
  • Interferon beta-1b every other day (Extavia) subcutaneous
  • Glatiramer acetate (Copaxone) daily subcuta¬neous injection

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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: 8/22/2014...#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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