Your browser does not support Javascript
email@mymsaa.org
Multiple Sclerosis Association of America Logo
Link to FaceBook Link to Twitter Link to YouTube Link to Pinterest
Register Why Register Contact MSAA Site Preferences Print Page Home
Improving Lives Today!
Donate Button
About MS
MS Overview
Newly Diagnosed
Symptoms
Treatments
Online Webinars & Videos
MSAA Publications
Prescription Assistance Programs
ACA Changes in Insurance
Toll-Free Helpline
Clinical Trial Information
Información en Español
FAQs



Home > About MS > Treatments for MS > Long-Term Treatments for MS
Share this Page:
submit to reddit

Long-Term Treatments for MS

The first three long-term treatments for multiple sclerosis (MS) became available in the early to mid 1990s and were dubbed the "A-B-C" drugs because of their brand names: Avonex®, Betaseron®, and Copaxone®. These are interferon beta-1a, interferon beta-1b, and glatiramer acetate, respectively. Another interferon, Rebif® (interferon beta-1a), was added to the list of approved treatments in 2002. This is the same drug as Avonex, but is injected differently and in more frequent and higher doses. In 2009, Extavia® (interferon beta-1b) was also approved. This is the same medicinal product as Betaseron and is given in the same doses, but is marketed under a different brand name and by a different pharmaceutical company.

In 2014, Plegridy™ (peginterferon beta-1a) was approved for the long-term treatment of relapsing forms of multiple sclerosis (MS). Plegridy is a pegylated version of interferon beta-1a. Pegylation is a chemical modification of a molecule (in this case the interferon beta-1a molecule) that extends its half-life, which refers to how long a drug stays active in the body before it is metabolized or eliminated.

All six of these disease-modifying therapies (DMTs) are approved by the Food and Drug Administration (FDA) for treating either relapsing-remitting MS (RRMS) or all relapsing forms of MS. Some of these DMTs have also been approved for "clinically isolated syndrome" (CIS), which refers to the initial symptom a patient reports prior to a diagnosis of MS.

Each of these treatments is administered by self injection at one's home, with the frequency of injections ranging from once weekly to once every two weeks, depending on the drug prescribed. These therapies have been used for several years and research shows that many people are doing well on these medications for extended periods of time (some for more than 20 years). Most side effects (such as flu-like symptoms and injection-site reactions) are manageable through various strategies and over-the-counter medications. Blood tests may be given periodically to monitor various items, such as liver enzymes, the number of red blood cells and white blood cells, and the possible development of neutralizing antibodies* (please see note below).

In 2000 (prior to the approval of some of the medications mentioned above), Novantrone® (mitoxantrone) was approved by the FDA for the long-term treatment of MS. This was the first drug indicated for RRMS, secondary-progressive MS (SPMS), and worsening RRMS. Novantrone has been used for many years to treat cancer. It is given via intravenous infusion once every three months. Side effects may include cardiac disease and leukemia, and for this reason, patients must be closely monitored and are limited to a maximum of two to three years of treatment with this drug. Because of the potential risks and with the approval of more long-term treatments for MS, Novantrone is seldom prescribed for individuals with MS.

Anyone taking Novantrone now or given Novantrone previously needs to have annual evaluations of his or her heart function (as noted in this advisory), even if no longer receiving this medication. To view this information on the FDA’s website, please see their “Opportunities for Collaboration” page under the “Drugs” section of their website (this may be found at http://www.fda.gov/Drugs/DrugSafety/SafeUseInitiative/ucm188762.htm). Please click on the listing for mitoxantrone (Novantrone) within the table of contents at the top of the page, or just scroll down to read the information.

In 2004, Tysabri® (natalizumab), was approved for relapsing forms of MS. It is administered via intravenous infusion every four weeks. After its initial approval, Tysabri was temporarily suspended after two individuals (taking Tysabri in combination with Avonex) developed progressive multifocal leukoencephalopathy (PML), which if not discovered early, is an often-fatal viral infection of the brain. Since that time, Tysabri has been re-approved and patients are closely monitored through the "TOUCH Prescribing Program."

In 2012, the United States Food and Drug Administration (FDA) announced that three factors have been identified with increasing the risk of PML for individuals with multiple sclerosis (MS) being treated with Tysabri. These include: (1) the presence of JC virus antibodies (detected through a blood test); (2) previous treatment with immunosuppressive drugs, such as Novantrone, Imuran, or Cytoxan; and (3) the length of time an individual has been taking Tysabri - specifically beyond the two-year mark. More details are included in MSAA's article, Antibody Test Identifies New Risk Factor for PML.

The eighth DMT for MS is Gilenya® (fingolimod), which was approved in September 2010. Pronounced as "Jil-EN-ee-ah," this is the first oral drug available for the long-term treatment of MS. The other approved treatments are given via self injections at home or infusions at a medical facility. The approval of an oral treatment provides a more convenient and comfortable option to some individuals, particularly if they do not respond to or are unable to tolerate the other approved medications. As with the other treatments, Gilenya also has potential side effects and adverse events, including a temporary slowing of the heart rate, edema (swelling) behind the eye, and liver changes.

In September 2012, Aubagio® (oral teriflunomide) became the ninth FDA-approved DMT for relapsing forms of MS -- and the second approved DMT that is taken orally. Aubagio has been approved in two dose levels: 7 mg and 14 mg. While the higher dose (14 mg) shows greater effectiveness, for individuals who may be more sensitive to the drug and experience greater side effects, the lower dose (7 mg) may be more appropriate. Common adverse events include headache, elevations in liver enzymes, hair thinning, diarrhea, nausea, neutropenia (a condition that reduces the number of certain white blood cells that normally fight infection), and paresthesia (tingling, burning, or numbing sensation). More severe adverse events include the risk of severe liver injury and the risk of birth defects if used during pregnancy.

Tecfidera® (dimethyl fumarate or DMF, formerly known as BG-12) was approved by the FDA as a first-line therapy for the long-term treatment of relapsing forms of MS in March 2013. This is the 10th DMT for the long-term treatment of MS. Tecfidera is administered in pill form orally and is the third oral DMT approved for MS. The approved dosage is 240 mg to be taken two times daily. The most commonly reported side effects are flushing and gastrointestinal events, occurring more often at the beginning of treatment, and decreasing in frequency after the first one to two months on this medication.

Individuals are usually prescribed only one type of DMT during any one time period. Several large clinical trials have been conducted to study each of these drugs separately for their safety and effectiveness in MS. Although differences exist in study design and specific findings, trials generally showed these common results:

  • Reduced the number of relapses
  • Reduced the severity of relapses
  • Reduced the development of new areas of inflammation as seen on magnetic resonance imaging (MRI) scans
  • Showed some evidence of delaying disease progression and/or disability

The documented effectiveness of each of these drugs varies to some extent, and differences can be attributed to the type of the drug, dose and administration, as well as variations in study design. Stronger drugs may offer greater effectiveness but may also pose greater health risks. Additionally, the effectiveness and side effects of each drug may vary from one patient to another, so individuals need to consult with their physician to determine which treatment might be the best option for them.

Each of the approved treatments has side effects that are usually manageable. At this time, Novantrone is the only drug that has a set limit of doses, which is necessary to avoid cardiotoxicity (heart damage). Tysabri increases the risk of PML (described above) and patients are closely monitored through the "TOUCH Prescribing Program." Patients beginning on Gilenya are monitored for changes in heart rate and are given baseline evaluations for any issues with the heart, lungs, liver, eyes and vision, as well as white-blood-cell count. The other drugs mentioned earlier appear safe provided the person taking the drug is not experiencing any adverse effects and blood tests continue to be normal.

While no damage to the reproductive system or the fetus has been observed, these drugs are not recommended if a woman is pregnant or considering pregnancy during her treatment period. Male patients considering certain long-term treatments may want to discuss options for family planning with their doctor.

Other treatments are sometimes used to try to slow MS disease progression when other therapies have been ineffective. Such treatments are approved by the FDA for other illnesses, but not specifically for the treatment of MS. These include intravenous immunoglobulin (IVIg) therapy, methotrexate, azathioprine (Imuran®), and cyclophosphamide (Cytoxan®).

Approved Long-Term Treatments for MS

All Additional Notes: Show - Hide

Print PDF of this Chart

Avonex

Type

Interferon beta-1a* (immune system modulator with antiviral properties)

Side Effects

Flu-like symptoms and headache

How Administered

30 micrograms taken via weekly intermuscular injection

Betaseron

Type

Interferon beta-1b* (immune system modulator with antiviral properties)

Side Effects

Flu-like symptoms, injection-site skin reaction, blood count and liver test abnormalities

How Administered

250 micrograms taken via subcutaneous injection every other day

Copaxone

Type

Synthetic chain of four amino acids found in myelin (immune system modulator that blocks attacks on myelin)

Side Effects

Injection-site skin reaction as well as an occasional systemic reaction - occurring at least once in approximately 10 percent of those tested

How Administered

20 (daily) or 40 (three-times weekly) milligrams taken via subcutaneous injection

Extavia

Type

Interferon beta-1b* (immune system modulator with antiviral properties)

Side Effects

Flu-like symptoms, injection-site skin reaction, blood count and liver test abnormalities

How Administered

250 micrograms taken via subcutaneous injection every other day

Plegridy

Type

Interferon beta-1a* (immune system modulator with antiviral properties)

Side Effects

Flu-like symptoms, injection-site skin reaction, blood count and liver test abnormalities

How Administered

125 micrograms taken via subcutaneous injection once every two weeks

Rebif

Type

Interferon beta-1a* (immune system modulator with antiviral properties)

Side Effects

Flu-like symptoms, injection-site skin reaction, blood count and liver test abnormalities

How Administered

44 micrograms taken via subcutaneous injection three times weekly

Novantrone

Type

Antineoplastic agent (immune system modulator and suppressor)

Side Effects

Usually well tolerated; side effects include nausea, thinning hair, loss of menstrual periods, bladder infections, and mouth sores; additionally, urine and whites of the eyes may turn a bluish color temporarily.

How Administered

IV infusion once every 3 months (for two to three years maximum)

Tysabri

Type

Humanized monoclonal antibody (inhibits adhesion molecules; thought to prevent damaging immune cells from crossing the blood-brain barrier)

Side Effects

Headache, fatigue, depression, joint pain, abdominal discomfort, and infection

How Administered

IV infusion every four weeks

Aubagio

Type

Immunomodulator (affecting the production of T and B cells; may also inhibit nerve degeneration)

Side Effects

Headache, elevations in liver enzymes, hair thinning, diarrhea, nausea, neutropenia (a condition that reduces the number of certain white blood cells), and paresthesia (tingling, burning, or numbing sensation)

How Administered

7- or 14-milligram tablet taken orally, once per day

Gilenya

Type

S1P-receptor modulator (blocks potentially damaging T cells from leaving lymph nodes)

Side Effects

Headache, flu, diarrhea, back pain, abnormal liver tests and cough

How Administered

0.5-milligram capsule taken orally once per day

Tecfidera

Type

Immunomodulator with anti-inflammatory properties; may have neuroprotective effects, potentially protecting the nerves and myelin covering from damage

Side Effects

Flushing and gastrointestinal events; reduced white-blood cell (lymphocyte) counts; elevated liver enzymes in small percentage of patients

How Administered

240 mg tablet taken twice daily

*Additional information about interferons: Some individuals develop neutralizing antibodies (NABs) to the interferons (Avonex, Betaseron, Rebif, and Extavia), but their impact on the effectiveness of these medications has not been established. Many continue to do well on these drugs despite the presence of NABs. Others may have sub-optimal results even without NABs present.

The MS Council and the American Academy of Neurology have concluded that the higher-dosed interferons are likely to be more effective than lower-dosed interferons. Several factors, however, must be considered when selecting one of these drugs, and this decision must be made on an individual basis under the guidance of a qualified physician.


Please note that MSAA does not endorse or recommend any specific drug or treatment. Individuals are advised to consult with a physician about the potential benefits and risks of the different treatment therapies.

For more information about approved and experimental treatments for MS, please refer to MSAA's MS Research Update, published in February 2014.

Last Updated on Tuesday, 19 August 2014 08:50