Treatments for Multiple Sclerosis (MS)

Approved 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.

All five 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 daily, 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 Rebif and Extavia 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.

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 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 newest 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.

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 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). 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®).

*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.
 

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.

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