Choices and Risks

The battle against multiple sclerosis (MS) has advanced considerably in recent years. A number of drugs are effective in alleviating symptoms and helping combat relapses. However, as with any disease, it’s crucial to first understand the benefits and risks of specific treatment options, and then work with your doctor to choose the therapy that’s best for you.

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There are several main groups of drugs used to treat MS. The groups are:

  • interferons, including interferon beta-1a and interferon beta-2a
  • biological drugs
  • monoclonal antibodies
  • pyrimidine synthesis inhibitor
  • sphingosine 1-phosphate receptor modulator
  • immunomodulator
  • antineoplastic drugs (also used to treat cancer)

Interferons

Avonex (interferon beta-1a)

Company: Biogen

Description: Avonex treats relapsing-remitting MS (RRMS) and was approved for use in the United States in 1996. Avonex is an interferon. Interferons are messenger proteins produced by the body to regulate the immune response. Avonex works to prevent the immune system from attacking the central nervous system. This reduces the number and severity of flare-ups. It has proven to be relatively safe and effective in reducing the progression of physical disability due to MS. It reduces the occurrence of relapses and reduces the number of lesions appearing on follow-up MRI. There is no generic version available.

Treatment: Intramuscular injection (into the muscle) once a week.

Side effects: Flu-like symptoms that typically lesson over time, including:

  • headache
  • fatigue
  • nausea or stomach pain
  • fever
  • body or muscle aches
  • chills
  • dizziness

Your doctor may recommend that you take an over-the-counter nonsteroidal anti-inflammatory drug (NSAID) to help reduce the discomfort from these side effects. 

Less common side effects include:

  • depression
  • mild anemia
  • irritation or rash at the injection site
  • liver abnormalities
  • allergic reactions
  • heart problems (rapid or slow heart rates, or chest pain)
  • thyroid problems
  • bone marrow suppression (lower counts of cells in the blood) 

Results: Studies investigating the treatment of RRMS with Avonex have shown a significant reduction in the number of people who have progressed to a disability score above 6.0 on the Kurtzke Expanded Disability Status Scale (EDSS).

Rebif (interferon beta-1a)

Companies: EMD Serono Inc. and Pfizer

Description: Rebif is approved for treatment of RRMSRebif is a type of interferon. Rebif is similar to Avonex, but it’s made by a different manufacturer and is dosed differently. Interferons are messenger proteins produced by the body to regulate the immune response. Rebif works to prevent the immune system from attacking the central nervous system. This reduces the number and severity of flare-ups. It has proven to be relatively safe and effective in reducing the progression of physical disability due to MS. It reduces the occurrence of relapses and reduces the number of lesions appearing on follow-up MRI. There is no generic version available.

Treatment: Subcutaneous injection (beneath the fat layer under the skin) three times per week.

Side effects: Flu-like symptoms that usually lessen over time, which can include:

  • headache
  • fatigue
  • nausea or stomach pain
  • fever
  • body or muscle aches
  • chills
  • dizziness

Your doctor may recommend that you take an over-the-counter NSAID to help reduce the discomfort from these side effects. 

Less common side effects include:

  • depression
  • mild anemia
  • irritation or rash at the injection site
  • liver abnormalities
  • allergic reactions
  • heart problems (rapid or slow heart rates, or chest pain)
  • thyroid problems
  • bone marrow suppression (lower counts of cells in the blood) 

Results: The drug, which has more than 17 years of clinical trial and patient use, is designed for those with RRMS. People who took the drug for two years showed a 78 percent reduction in lesions, a reduced need for steroid treatments, and fewer exacerbations. The Food and Drug Administration (FDA) approved Rebif Rebidose in early 2013. It consists of a color-coded auto-injector for convenience.

Plegridy (peginterferon beta-1a)

Company: Biogen

Description: Plegridy is approved for RRMS. It’s a “pegylated” form of interferon, in which a chemical called polyethylene glycol is attached to the drug molecules. This helps the drug maintain its effects in the body for a longer amount of time. Its action is similar to other beta-1a interferons, but it stays active in the body much longer. There is no generic version available.

Treatment: Subcutaneous injection (beneath the fat layer under the skin) in your stomach (abdomen), back of upper arm, or thigh every two weeks using the Plegridy Pen auto-injector or a prefilled syringe.

Side effects: Common side effects include flu-like symptoms, including:

  • headache
  • chills
  • muscle aches
  • weakness
  • fever
  • injection site itching, swelling or pain (Use a different place for the injection each time to reduce this effect.)
  • nausea or vomiting

More serious side effects can include:

  • liver problems 
  • worsening of liver problems that should be monitored by a doctor
  • suicidal thoughts and depression
  • seizures
  • congestive heart failure in patients with pre-existing cardiac disease
  • bone marrow suppression (lower counts of cells in the blood) 

Results: The FDA approved Plegridy for use as a disease-modifying therapy in August 2014. It’s designed to maintain the effects of interferon in the body for a longer period of time than previously available versions of interferon. People in the study showed a 67 percent reduction in new or newly enlarging lesions in a clinical trial. They also showed a 36 percent reduction in relapse rate compared to placebo at 48 weeks, according to the prescribing information.

Interferon beta-1b

Betaseron (interferon beta-1b)

Company: Bayer HealthCare Pharmaceuticals

Description: Betaseron is an interferon and was approved for use by the FDA in 1993 to treat RRMS. It has been shown to be effective in people who had their first clinical episode or who have features of MS confirmed by MRI. Interferon beta is a protein that’s normally manufactured by the body. The drug is made from human blood plasma. It works by reducing the body’s immune response that attacks nerve cells. It reduces inflammation by reducing the immune response in the central nervous system. It also reduces the number and severity of flare-ups and stabilizes the lesions (or nerve damage) as well. There is no generic form available.

Treatment: Subcutaneous injection (under the skin), every other day. The outer surfaces of the arms, abdomen, hips, and thighs may be used, rotating sites each time. 

Side effects: Flu-like symptoms that typically lessen over time. These can include:

  • headache
  • fatigue
  • nausea or stomach pain
  • fever
  • body or muscle aches
  • chills
  • dizziness

Your doctor may recommend that you take an over-the-counter NSAID to help reduce the discomfort from these side effects. It’s also common to have injection site reactions, such as itching, redness, or pain. 

Less common side effects can include: 

  • more severe injection site reactions, such as hives
  • depression
  • liver abnormalities
  • allergic reactions
  • low white blood cell count
  • seizures
  • thyroid problems

Results: One clinical trial found that the drug reduces onset of MS by 50 percent in the first two years among people with MS who display clinically isolated syndrome (CIS).

Extavia (interferon beta-1b)

Company: Novartis Pharmaceutical

Description: Extavia is very similar to Betaseron. It reduces inflammation and the frequency and severity of attacks. It was approved for use in 2009 to treat RRMS. It has been shown to be effective in patients who had their first clinical episode or who have features of MS confirmed by MRI. There is no generic version available.

Treatment: Subcutaneous injection (under the skin), every other day. The outer surfaces of the arms, abdomen, hips, and thighs may be used, rotating sites each time. 

Side effects: You may have flu-like symptoms that typically lessen over time. These can include:

  • headache
  • fatigue
  • nausea or stomach pain
  • fever
  • body or muscle aches
  • chills
  • dizziness

Your doctor may recommend that you take an over-the-counter NSAID to help reduce the discomfort from these side effects. It’s also common to have injection site reactions, such as itching, redness, or pain. 

Less common side effects can include: 

  • more severe injection site reactions, such as hives
  • depression
  • liver abnormalities
  • allergic reactions
  • low white blood cell count
  • seizures
  • thyroid problems

Results: In a clinical study, the percent of MRIs showing new or expanding lesions was 29 percent in the placebo group and 6 percent in the group receiving treatment.

Biological Drugs   

Copaxone (glatiramer acetate)

Company: Teva

Description: Copaxone is a biological drug, approved for use in 1996 to treat RRMS. It’s made of manufactured proteins that are similar to myelin, the natural protein that wraps nerve cells. It blocks the activity of T cells, which are white blood cells. T cells play a role in damaging the myelin wrapper around nerves. Although the way it works isn’t entirely clear, it’s believed to act as a sort of decoy for the attention of inflammatory cells. Copaxone may also stimulate cellular activity that prevents damage to nerve fibers.

Generic version available: Glatopa, glatiramer acetate 20 mg/mL injection made by Sandoz, was approved on April 16, 2015.    

Treatment: Subcutaneous injection (just beneath the fat layer of the skin), once per day. Copaxone is available in two strengths (20 mg/mL and 40 mg/mL) and is dosed either once a day or three times a week, as determined by your doctor. 

Side effects:

  • injection site reactions
  • dilation of blood vessels
  • chest pain  
  • tremor (involuntary shaking)
  • weakness
  • nausea or vomiting
  • back pain
  • runny nose or cough
  • headache
  • skin rash

Some people experience chest pain as long as a month after starting the drug. Call your doctor if you experience this.

A post-injection reaction may occur in a small minority of patients. It can last about 15 minutes and may consist of:

  • anxiety
  • chest pain
  • heart palpitations
  • flushing
  • shortness of breath

Call your doctor right away if you have this reaction. This reaction usually happens just once and will disappear on its own, but you must talk to your doctor about whether you should continue the drug if you have this reaction. 

Results: The synthetic polypeptide has a consistent track record of improving immune system function and reducing exacerbations. Long-term drug study results show that Glatiramer cut the relapse rate in half during the first year of treatment, and for two thirds of patients, the EDSS scores remained stable or improved over the entire 10 year follow-up period. Copaxone also requires fewer lab tests for safety monitoring than other treatments for RRMS. 

Pyrimidine Synthesis Inhibitor

Aubagio (teriflunomide)

Company: Sanofi/Genzyme

Description: Aubagio is a disease-modifying therapy. The FDA approved it in September 2012 for the treatment of RRMS. It’s a pyrimidine synthesis inhibitor. This reduces the number of white blood cells and also reduces inflammation. It may reduce the number of active white blood cells in the central nervous system and prevent damage to nerve cells in MS. The exact method of action is unknown. 

Treatment: Oral tablet taken once daily.

Side effects:

  • headache
  • changes in liver function test results
  • diarrhea
  • thinning hair
  • nausea
  • pain
  • tingling sensation in fingers or toes (peripheral neuropathy)
  • increased blood pressure

Serious side effects may include:

  • liver toxicity
  • bone marrow suppression (reduced number of white or red blood cells)
  • increased risk of infections, such as tuberculosis
  • respiratory effects, including infections or bronchitis 

Aubagio should not be taken by women who are pregnant or who might soon become pregnant. Like other potent disease-modifying agents, this drug can increase the risk of certain infections. You should be tested for tuberculosis before starting therapy. Regular monitoring of liver function and blood pressure should also be done.

Results: Trials show that Aubagio can significantly reduce the rate of relapses. The higher dose of the drug has also been shown to reduce disability progression, compared to placebo. Aubagio is related to a similar drug used to treat the autoimmune disease, rheumatoid arthritis.

Sphingosine 1-Phosphate Receptor Modulators

Gilenya (fingolimod)

Company: Novartis Pharmaceutical

Description: Gilenya is a sphingosine 1-phosphate receptor modulator (S1P-receptor modulator). It’s similar in structure to naturally occurring cell surface receptors. This means it keeps destructive T cells from leaving the lymph nodes and crossing the blood-brain barrier, where they can attack nerves in the central nervous system. 

The FDA approved Gilenya in November 2010 to treat adults with RRMS to reduce the frequency of relapse and delay physical disability. There is no generic version.

Treatment: Capsule taken orally every day.

Side effects:

  • headache
  • flu-like symptoms
  • diarrhea
  • back pain
  • liver enzyme elevations
  • cough

Serious side effects can include:  

  • slowed heart rate following the first dose
  • increased risk of infections, including influenza, herpes, and bronchitis
  • swelling within the eye that could affect vision

You must undergo heart function monitoring for at least six hours when you first start the drug. This is because of the possibility of a dangerously slow heartbeat. People with pre-existing heart disease shouldn’t take the medication. Some other prescription drugs can increase this effect. Tell your doctor about all the drugs you’re taking before taking fingolimod. 

Results: The drug is the first in a new class of immune modulating (regulating) drugs, which reduce damage to the central nervous system and increase the repair of damaged neurons. Gilenya has shown the ability to reduce relapse rates by 60 percent and reduce the progression of MS by up to 82 percent when measured with an MRI.

Monoclonal antibody

Lemtrada, Campath (alemtuzumab)

Company: Sanofi/Genzyme

Description: Lemtrada (another brand is Campath-1H) is a humanized monoclonal antibody that attacks CD52, which is a protein found on the surface of dangerous white blood cells. Lemtrada is used to treat adults with RRMS. It was originally approved to treat a type of leukemia at a much higher dosage. When used to treat leukemia, the drug would help destroy cancer-causing cells.

Though the mechanism of this drug’s effect on MS is not known, scientists believe it binds to CD52 sites on white blood cells, which makes those and other white blood cells break down. This could help prevent those cells from damaging nerves. 

Because it can cause several serious side effects, the FDA recommends that alemtuzumab only be prescribed to people who have had a poor response to at least two other MS drugs first. There is no generic version.

Treatment: The recommended dose is given just two times, one year apart. Intravenous infusions are given over four hours, for five days in a row. A second treatment for another three days is given one year later.   

Side effects:

  • rash
  • headache
  • fever
  • nausea and/or vomiting
  • fatigue
  • nasal congestion
  • insomnia

Serious side effects from taking this drug have occurred and some patients have died. This medication has a boxed warning, which is the most serious drug warning the FDA provides. These side effects include:

  • Serious autoimmune conditions have happened to people treated with this drug. These include immune thrombocytopenia (severely reduced numbers of platelets, which help blood clot) and anti-glomerular basement membrane disease, which causes damage to the kidneys. 
  • Bone marrow suppression, which means the body can’t make enough white or red blood cells.
  • Serious or fatal infections can occur, caused by bacteria, viruses, fungi, or protozoa (single-celled organisms). You may be given preventative treatment for some infections, if you are given this drug for MS.
  • Infusion reactions can occur. These are reactions to the intravenous treatment itself and can happen during treatment and for up to 24 hours afterward. 
  • Higher risk of cancer, including thyroid cancer, melanoma, and other cancers. 
  • A number of people have developed autoimmune thyroid disease after taking this drug. Your doctor should monitor your thyroid function carefully if you are given this drug. 

More detail about side effects is included in the product’s prescribing information.

Due to these warnings, alemtuzumab is only available through a risk evaluation and mitigation strategy (REMS) program. The REMS program ensures that patients are well educated about monitoring their health while being treated with this drug. If you take this drug, you’ll need monthly blood tests for at least four years after you receive your last dose. 

Results: Lemtrada required extra clinical trials before it was approved by the FDA in November 2014. It was compared to EMD Serono’s MS drug, Rebif, in two phase 3 trials. It showed a superior effect at preventing MS relapses and also did a better job of preventing disability over a two-year period. People taking Lemtrada were roughly 55 percent less likely to relapse over a two-year period compared to patients taking Rebif in one clinical trial, according the product’s prescribing information. It hasn’t been compared directly to other disease-modifying treatments.

Tysabri (natalizumab)

Companies: Biogen and Perrigo (formerly Elan Pharmaceuticals)

Description: Tysabri is approved for the treatment of RRMS. It’s generally used for people who have seen no improvement with other MS treatments. Tysabri is a laboratory-produced monoclonal antibody that prevents certain while blood cells from attaching and moving from the blood into the central nervous system. There is no generic version of this drug available.

Treatment: Given as an intravenous infusion in a medical facility every four weeks.

Side effects:

  • headache
  • fatigue
  • depression
  • urinary tract infections
  • vaginal infections
  • lower respiratory tract infections (pneumonias)
  • joint pain
  • chest discomfort

Serious side effects include allergic or hypersensitivity reactions after intravenous infusion. Symptoms can include:

  • fever
  • rash
  • dizziness
  • nausea
  • flushing
  • low blood pressure
  • breathing difficulties
  • chest pains

It’s also important to test for progressive multifocal leukoencephalopathy (PML). PML is a rare but often fatal brain infection, which is caused by the John Cunningham virus (JCV). Due to these warnings, natalizumab is only available through a REMS program. The REMS program ensures that patients are well educated about monitoring their health while treated with this drug.   

Results: The FDA approved Tysabri in 2005. Studies show that the drug can slow progression of disability and help reduce relapses. It may also help reduce fatigue and improve cognitive functioning related to MS. Tysabri reduced the rate of clinical relapse at one year by 68 percent in one study. The drug also resulted in 92 percent fewer lesions compared to placebo at both one and two years as measured by MRI.

Antineoplastic Drug

Mitoxantrone 

Companies: Fresenius Kabi, Hospira, Pfizer, and Teva 

Description: Mitoxantrone is an immunosuppressant drug originally used to treat certain types of cancer. It’s also approved for use in people with progressive-relapsing MS (PRMS), secondary-progressive MS (SPMS), and worsening RRMS. It hasn’t been approved for the treatment of primary-progressive MS (PPMS). The drug decreases lesions and stabilizes MS in some people. This drug is available only in generic form.

Treatment: Intravenous infusion in a medical facility four times a year. For safety reasons, the use of this drug is limited. The lifetime dosage limit is typically between eight to 12 doses over two to three years.

Side effects:

  • changes in heart rhythm and function
  • water retention (bloating)
  • discolored urine following administration
  • infections
  • bone marrow suppression
  • nausea and/or vomiting
  • hair thinning
  • bladder infections
  • mouth sores

It’s also necessary to monitor for signs of serious liver and heart damage, changes in kidney function, cardiac disease, and leukemia. Also, the medication may cause possible transient (blue) discoloration of the whites of the eyes and the urine. There is a lifetime limit on how much of the drug a patient may receive because of the risk of cumulative damage to heart muscle. Due to serious side effects, this drug is reserved for patients with rapidly progressing MS who have not had good results with at least two other treatments, according to The American Academy of Neurology

Results: The drug works by suppressing the immune system. This decreases inflammatory damage to the myelin that surrounds nerves. It’s used for relapsing-remitting, progressive-relapsing, and secondary-progressive forms of MS. The drug was approved in 2000. It has a track record of improving EDSS scores and reducing relapses. In a clinical trial, 90 percent of patients taking the drug in combination with methylprednisolone showed no sign of lesions after six months.

Immunomodulators

Tecfidera (dimethyl fumarate)

Company: Biogen

Description: Tecfidera is the third approved oral disease-modifying drug for MS, according to the National MS Society. It was approved in March 2013 for people with RRMS. It was formerly known as BG-12. The action of dimethyl fumarate in MS is not certain, but it may prevent oxidative stress. Also, it may prevent inflammation and protect cells using a pathway that involves antioxidant properties. There is no generic version available.

Treatment: Oral capsule (120 mg) two times a day for seven days, followed by one 240 mg capsule twice daily.

Side effects: Tecfidera may decrease a person’s white blood cell count and increase the risk of infection. The FDA recommends that doctors monitor a patient’s white blood cell count annually. Common side effects include:

  • flushing and redness
  • diarrhea
  • itching
  • rash
  • nausea

More serious potential side effects include:

PML:

PML is a rare but often fatal brain infection, which is caused by the JCV virus. It usually occurs only in people who are immunocompromised or being treated with immune suppressing drugs. 

Reduced white blood cell count:

A reduced white blood cell count could increase the risk of infections.

Anaphylaxis or angioedema:

Serious allergic reaction, swelling, and difficulty breathing. 

Results: In two clinical trials Tecfidera treatment resulted in fewer MS relapses compared to people taking placebo. This included a 49 percent reduction in relapse compared to placebo in one trial, according to the product’s prescribing information.