Treatments
Approved Long-Term Treatments
The first three long-term MS treatments to be approved 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. All were approved by the Food and Drug Administration (FDA) for treating RRMS. These drugs have been approved by the Food and Drug Administration (FDA) for treating either RRMS or all relapsing forms of MS. Some of the drugs have also been approved for “clinically isolated syndrome” (CIS), which refers to the initial symptom a patient reports prior to a diagnosis of MS.These drugs have been used for several years and research shows that people are doing well on these medications for long periods of time (some for more then 20).
The fourth drug to be approved by the FDA was Novantrone® (mitoxantrone), and this was the first drug indicated for RRMS, SPMS and worsening RRMS. News then arrived of a fifth FDA-approved drug Rebif® (interferon beta-1a) for relapsing types of MS. This is the same drug as Avonex, but is injected differently and in more frequent and higher doses.The sixth drug now available for MS is Tysabri® (natalizumab), which is approved for relapsing forms of MS.
Several large clinical trials have been conducted to study each of these drugs separately for their effects on 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 MRI
- Showed some evidence of delaying short-term disease progression
Each of the approved treatments has side effects which 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). After its original approval, Tysabri was temporarily suspended after two individuals (taking Tysabri in combination with Avonex) developed progressive multifocal leukoencephalopathy (PML), which 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.” The other drugs 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 should 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®).
Six Approved Long-Term Treatments for MS
| Drug | Type | Side Effects | How Administered | Notes |
|---|---|---|---|---|
| Betaseron | Interferon beta-1b* (immune system modulator with antiviral properties) | Flu-like symptoms, injection-site skin reaction, blood count and liver test abnormalities | 250 micrograms taken via subcutaneous injections every other day | Side effects may be prevented and/or managed effectively through various treatment strategies; side effect problems are usually temporary. |
| Avonex | Interferon beta-1a* (immune system modulator with antiviral properties) | Flu-like symptoms and headache | 30 micrograms taken via weekly intermuscular injections | Side effects may be prevented and/or managed effectively through various treatment strategies; side effect problems are usually temporary. |
| Rebif | Interferon beta-1a* (immune system modulator with antiviral properties) | Flu-like symptoms, injection-site skin reaction, blood count and liver test abnormalities | 44 micrograms taken via subcutaneous injections three times weekly | Side effects may be prevented and/or managed effectively through various treatment strategies; side effect problems are usually temporary. |
| Copaxone | Synthetic chain of four amino acids found in myelin (immune system modulator that blocks attacks on myelin) | Injection-site skin reaction as well as an occasional systemic reaction - occurring at least once in approximately 10 percent of those tested | 20 milligrams taken via daily subcutaneous injections | Systemic reactions occur about five to 15 minutes following an injection and may include anxiety, flushing, chest tightness, dizziness, palpitations, and/or shortness of breath. Usually lasting for only a few minutes, these symptoms do not require specific treatment and have no long-term negative effects. |
| Tysabri | Humanized monoclonal antibody (inhibits adhesion molecules; thought to prevent damaging immune cells from crossing the blood-brain barrier) | Headache, fatigue, depression, joint pain, abdominal discomfort, and infection |
IV infusion every four weeks | Risk of infection (including pneumonia) was the most common serious adverse event during the studies (occurring in a small percentage of patients). The TOUCH Prescribing Program monitors patients for signs of PML, an often-fatal viral infection of the brain, which occurred in a total of three patients taking Tysabri in combination with Avonex. |
| Novantrone | Antineoplastic agent (immune system modulator and suppressor) | 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 | IV infusion once every 3 months (for two to three years maximum) | Novantrone carries the risk of cardiotoxicity (heart damage) and may not be given beyond two or three years. People undergoing treatment must have regular testing for cardiotoxicity, white blood cell counts, and liver function. Novantrone was studied in combination with large IV doses of steroids. Concurrently, many physicians often use it in combination with one of the interferons or Copaxone. |
Additional information about interferons: Some individuals develop neutralizing antibodies (NABs) to the interferons (Avonex, Betaseron, and Rebif), 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.
Treating Exacerbations with Steroids
Most people with MS experience exacerbations (or MS attacks) which often last from one to three months. Acute physical symptoms and neurological signs must be present for at least 24-to- 48 hours, without any signs of infection or fever, before the treating physician may consider it to be a true relapse.
A pseudoexacerbation is a temporary worsening of symptoms, without actual myelin inflammation or damage, which is brought on by external influences — such as infection, exhaustion, heat, depression, or stress. Checking for a fever is important, since even a minor infection can cause old symptoms to reappear. Urinary tract infection (UTI) is the most common illness to cause a pseudoexacerbation. People with "heat-sensitive" MS should avoid hot tubs, saunas, or other situations that can raise the body's temperature. These too can cause a temporary increase in symptoms.
Exacerbations are usually treated with a high-dose, short-term course of powerful steroids (corticosteroids). The goals are to (1) reduce the severity and duration of the relapse by decreasing inflammation, and (2) potentially minimize any permanent damage resulting from the attack. Steroid treatments are often given by IV injection (intravenously), which injects the drug directly into the bloodstream for quick action. In the past, this could only be done in a hospital setting, but now this treatment may be performed in the comfort of one's home.
Long-term use of steroids is not generally recommended. They can cause many side effects when given over a long period of time and may have no effect on the long-term progression of MS.
