Understanding Multiple Sclerosis
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 now the treatments of choice 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, 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 given by subcutaneous (under the skin) injections.
The best results are in patients in early stages, 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. About 15% of patients have side effects, usually 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, and 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. Patients who take natalizumab must enroll in a special program called TOUCH, which is run by the drug's manufacturer. Patients need to get magnetic resonance imaging (MRI) brain scans before they begin taking the drug, and they are evaluated regularly during drug treatment to make sure they are not at risk of developing PML. The risks for PML are reduced when natalizumab is given alone and not in combination with other immunomodulatory medications.
Natalizumab may also cause liver abnormalities. Cases of liver injury have been reported within a week after a first dose of natalizumab, as well as after multiple doses. 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 (Copaxone).
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.