Interferon Beta Drugs
Interferons (so-called because they “interfere” with viral replication) suppress inflammatory factors in the immune system that are associated with the attack on myelin. Interferon drugs are the main treatments for relapsing-remitting MS. Doctors recommend that these medications be used early in the course of the disease and continued indefinitely, unless they produce no benefits or have severe side effects. When the drug is discontinued, disease activity may increase.
Brands. Interferon drugs used for MS are interferon beta-1b (Betaseron, Extavia) and interferon beta-1a (Avonex, Rebif). Avonex and Rebif are the same chemical, but Avonex is given as weekly intramuscular injection and Rebif is taken as subcutaneous injections three times a week.
Side Effects. Side effects include:
- Flu-like symptoms. Flu-like symptoms (fever, chills, sweating, muscle aches, and fatigue) following injection are a common complaint. These symptoms usually lesson over time. Taking acetaminophen (Tylenol) before the injection can help.
- Injection site reactions. Pain, redness, and swelling can occur at the injection site. Applying ice or a cool compress to the skin a few minutes before injection can help prevent pain.
- Less common side effects include allergic reactions, depression, mild anemia, low white blood cell counts, and liver abnormalities. Patients who take interferon drugs should have a baseline liver function test at the start of treatment and receive periodic testing afterwards. Patients should avoid alcohol.
Neutralizing Antibodies That Reduce Effectiveness. Over time, people taking interferons develop antibodies to the drugs, some of which can neutralize their effects. The risk for neutralizing antibodies (NAbs) increases with higher doses and greater frequency of use. Interferons injected under the skin (Betaseron, Rebif) are more likely to produce neutralizing antibodies than Avonex, which is injected into a muscle. Patients who have this reaction may be treated with an alternative interferon or with glatiramer, which has an extremely low risk, for NAbs. Often after switching drugs, NAb levels decline, and the patient may be able to return to the original interferon.
Glatiramer Acetate (Copaxone)
Glatiramer acetate (Copaxone) is a synthetic molecule that resembles a basic protein found in myelin. It is used as a decoy to trick white blood cells into attacking it instead of myelin. It is approved to help reduce the frequency of relapses in patients with relapse-remitting MS. It comes in pre-filled syringes and is given by subcutaneous (under the skin) injections.
The best results are for patients in early stages of MS, but the longer patients remain on the drug, the greater the improvement. Benefits have lasted for years. Glatiramer acetate appears to work as well as interferon beta drugs in decreasing the number and severity of relapses, but it may have less effect on lesions.
Side Effects. Side effects may occur right after the injection. They include pain at the injection site, chest pain, rapid heartbeat, flushing, anxiety, and shortness of breath.
Natalizumab (Tysabri) is a monoclonal antibody drug approved for treatment of MS. Monoclonal antibodies (MAbs) are drugs that target specific antibodies involved with the immune response. Natalizumab should only be taken by patients who have not responded to or who cannot tolerate other disease-modifying drugs. Natalizumab can only be taken alone, not in combination with other immune-modifying drugs. The drug is given by IV infusion once every 4 weeks.
Many patients who take natalizumab have reported great improvement in reduction of MS relapses and the drug appears to work well in slowing disease progression. However, natalizumab does carry risks for potentially serious side effects.
Common Side Effects. Common side effects include headache, fatigue, depression, joint pain, abdominal and chest discomfort, along with urinary tract, pneumonia, and other infections.
Severe Side Effects. Patients who take natalizumab must be monitored for signs of progressive multifocal leukoencephalopathy (PML). PML is a rare neurological disease that can affect people with compromised immune systems.
Three factors increase the risk for PML:
- The presence of anti-JCV antibodies. The John Cunningham (JC) virus is a common and normally harmless virus. However, in people with weakened immune systems, the JC virus can cause PML. PML only occurs in people who have been exposed to the JC virus. Your doctor can use the Stratify JCV Antibody ELISA blood test to determine if you have JC virus antibodies (a sign of exposure). If you test negative, you should continue to be tested regularly while taking natalizumab. If you test positive, discuss with your doctor your risks of developing PML while on natalizumab.
- Longer duration of natalizumab treatment. The risk for PML appears to increase when patients receive more than 24 natalizumab infusions (2 years of treatment).
- Prior treatment with an immunosuppressant drug (such as mitoxantrone, azathioprine, methotrexate, cyclophosphamide, or mycophenolate) increases the risk for PML. .
Symptoms of PML may include progressive weakness on one side of the body, clumsiness of limbs, vision disturbances, and changes in thinking, memory, and orientation that may result in confusion or personality changes. If PML is suspected, a magnetic resonance imaging (MRI) scan can confirm early stages of the disease. Patients should also get an MRI brain scan prior to starting natalizumab treatment to evaluate pre-existing brain lesions.
Natalizumab may also cause liver damage. Signs of liver injury include yellowing of skin and eyes (jaundice), sudden darkening of urine, fatigue, and nausea and vomiting. Patients should immediately contact their doctors if any of these symptoms develop. If blood tests confirm liver injury, natalizumab should be discontinued.
Mitoxantrone (Novantrone) was the first drug approved specifically for secondary-progressive MS and progressive-relapsing MS. It is also used to treat worsening relapsing-remitting MS. Mitoxantrone is often used in combination with an interferon beta drug or glatiramer acetate.
Cumulative doses can have toxic effects on the heart, including heart failure, so the drug is only used for a limited period of 2 - 3 years. Patients should have a heart evaluation, including evaluation of left ventricular ejection fraction (LVEF), before starting this drug and before each dose administration. Mitoxantrone can also increase the risk for leukemia.
Side Effects. In addition to risks of heart damage, common side effects of mitoxantrone include nausea, thinning hair, bladder infections, mouth sores, and loss of menstrual periods. Patients may experience a temporary bluish color to their urine or eyes during the first 24 hours after IV infusion.
Fingolimod (Gilenya) was the first oral drug approved to treat relapsing forms of MS. [The other two oral drugs are teriflunomide (Aubagio) and dimethyl fumarate (Tecfidera).] Fingolimod is taken once-daily as a pill.
Common Side Effects. Common side effects may include headache, influenza, diarrhea, back pain, cough, and abnormal liver enzymes.
Severe Side Effects. Fingolimod can decrease heart rate (bradycardia, or bradyarrythmia) especially after the first dose. (The doctor should monitor the patient for 6 hours after the first dose to make sure there are no heart problems.) Heart rates usually stabilize within a month after starting fingolimod. Because of these cardiac side effects, patients with certain pre-existing heart conditions or recent history of heart attack or stroke should not use fingolimod.
Other serious side effects include macular edema (fluid accumulation in a part of the eye’s retina), increased risk of serious infections, and shortness of breath. Fingolimod can cause liver problems; patients should have liver tests before starting the drug. This drug may cause birth defects. Women of childbearing age who take fingolimod should use birth control while on the drug.
Teriflunomide (Aubagio) was the second approved oral treatment for relapsing forms of MS. Like fingolimod, teriflunomide is taken as a once-daily pill.
Common Side Effects. Teriflunomide may cause diarrhea, upset stomach, flu-like symptoms, and a burning sensation in skin. Hair thinning and loss may occur.
Severe Side Effects. Teriflunomide can cause serious liver problems and should not be taken by patients with liver disease. The drug can lower white blood cell counts, which increases the risk for infections. Teriflunomide can affect a man’s sperm and it can cause birth defects in pregnant women. Both men and women who take teriflunomide should use contraception while taking this drug.
Dimethyl Fumarate (Tecfidera)
Dimethyl fumarate (Tecfidera) is the newest of the three oral drugs approved for treating relapsing forms of MS. Dimethyl fumarate is taken twice daily as a pill.
Common Side Effects. Like fingolimod and teriflunomide, this drug can cause upset stomach and diarrhea. This drug may also cause skin flushing and stomach pain.
Severe Side Effects. Dimethyl fumarate may lower white blood cell counts although it does not appear to seriously increase the risk for infections. It is uncertain if dimethyl fumarate causes birth defects or can be passed along in breast milk. This drug was approved in 2013, so its side effects may not yet be fully known.