Available Treatments for Multiple Sclerosis (MS)
We are at a very exciting juncture in the treatment of MS. For the first time we have medications available to us that can alter the natural course of the disease. Often referred to as the “ABC” drugs, Avonex, Betaseron, and Copaxone are medications designed to decrease the number of MS exacerbations, which include episodes of severe weakness, numbness, and disability. We also have at our disposal many more medications that can be used to treat the symptoms of MS, such as spasticity and fatigue. The future of MS treatment looks even more promising, as there are numerous clinical trials currently underway throughout the world. This is a very active time in clinical MS research. It is becoming increasingly evident that early treatment with these drugs is important in the long-term management of MS.

ABC Medications
The ABC drugs are those which act on the immune system to decrease the number of attacks in MS. They act to “quiet down” the immune system by different biologic mechanisms. However, they all decrease the number of flares by approximately one-third. They are each administered slightly differently. You and your doctor should discuss which medication might be best for you.

Avonex (Beta-interferon-1a)
This medication is delivered as a once-a-week intramuscular injection. It has been shown to decrease the number of exacerbations by a third as well as the number of new MS lesions (areas of cellular inflammation or destruction) shown on an MRI (use of a magnetic field to view internal soft tissues such as organs, muscles, and nerves). It has also been shown to decrease the disability associated with MS, which include weakness, gait disturbance, visual problems, and cognitive impairments. The side effects include flu-like symptoms such as fever, chills, and muscle aches that occur for several hours after the injection. They usually improve after using the medication for several weeks to months. Using acetaminophen (Tylenol) or ibuprofen (Motrin) prior to taking the injection can alleviate the symptoms.

Betaseron (Beta-interferon-1b)
Betaseron has been shown to decrease the number of attacks in MS by a third and to decrease new lesion appearance on MRI. It also has been shown in one clinical trial to be effective in secondary progressive MS (a specific form of MS that is characterized by gradual progression rather than recurrent exacerbations and remissions). It is given as an every-other-day subcutaneous injection. Its side effects also include flu-like symptoms and injection site reactions.

Copaxone (Glatiramer acetate or Copolymer-1)
This is delivered as a once-daily subcutaneous injection and also is proven to decrease the number of MS attacks by a third. It is usually very well tolerated as it does not have the flu-like side effects that the interferons do. However, 20 percent of patients may experience a short-lived anxiety-like reaction after injection. Injection site reactions (pain, tenderness, minor swelling, redness) are also common with Copaxone.

Each of these medications has advantages and disadvantages. The decision whether to even start one of these medications, or which one to begin with is an individual choice that must be made in consultation with your physician. The way we prescribe these medications is to present our patient with all of the treatment options and information, and help them to decide which is best for them. Although we feel that early treatment is beneficial, there may be instances in which the patient and/or doctor decide to delay treatment, such as pregnancy.

Clinical Criteria for a Diagnosis of MS: If a Patient has one of the Symptoms, Should He or She Begin Treatment?
One recent study, the CHAMPS trial looked at this issue. It evaluated the use of Avonex in patients who were not yet diagnosed with MS, but who were at high risk for developing MS. In other words, they had one clinical attack and signs of MS on their MRI scans. The results indicated that those patients who were started on Avonex, as compared to placebo (sugar pill), had a delayed onset of the next clinical attack. There was a 44-percent reduction in the rate of developing MS in the patients treated with Avonex. This news is quite exciting, and is further proof that early treatment is an important consideration in MS. MS physicians, however, have yet to come to a complete consensus about when is the most appropriate time to start treatment, and again this remains a personal decision between you and your physician.

Steroid Use for MS
Although not proven to change the long-term outcome, or disability in MS, steroids have been shown to hasten recovery from a flare (exacerbation). That said, they are not without side effects, and not every flare should be treated with steroids. Steroids are anti-inflammatory drugs that help decrease the inflammatory process in MS. They are usually reserved for more disabling attacks that have a major impact on daily function, such as those involving vision or ability to walk. It is important to call your doctor if you think that you are having a flare and talk to him or her about whether or not treatment would be a good idea. The steroids can be administered intravenously or by mouth, depending on your doctor's preference and the severity of the attack. The duration of steroid treatment is usually brief, from days to a maximum of several weeks, again depending on the severity of the attack. The intravenous steroids can be administered in the hospital or at home with the help of a visiting nurse. That is also a decision that you will have to make with your doctor. Side effects of short-term steroid use are mood-swings, insomnia, elevated glucose, and weight gain. These side effects will stop once the steroids have been discontinued.

Medications that can Relieve MS Symptoms
Stiffness/spasticity: Baclofen (Lioresal) is an excellent medication for muscle spasms. It can be taken several times per day, and adjusted for those times when your symptoms are at their worst. It can cause some sedation, as well as muscle weakness, since it acts to relax the muscles. For this reason, it must be started at a low dose and increased in small, incremental doses up to the lowest dose that relieves the symptoms. If baclofen does not prove to be effective enough, another medication can be used alone, or in conjunction with baclofen. It is a newer medication, called tizanidine (Zanaflex). It is quite potent, and must be started at a low dose, and increased slowly, as it is very effective in controlling spasms, but is more likely to cause weakness. Finally, a third drug called dantrolene (Dantrium) is sometimes used if the other medications are not effective enough.

Neuropathic pain: There are numerous medications that can be used to treat the pain syndromes that MS causes. There are many medications that are not narcotics nor habit-forming that can help to alleviate the pain in the long-term. These include anti-epileptic drugs such as gabapentin (Neurontin), anti-depressants such as amitriptyline (Elavil) and the newer antidepressants such as sertraline (Zoloft) and paroxetine (Paxil). Although these were traditionally used to treat depression, they have also been found to work in chronic pain syndromes.

Fatigue: Amantidine (Symmetrel) is a medication that can be used to treat the sensation of generalized fatigue in MS. It does not work in the muscle fatigue that occurs with over-exertion, but rather, in the feeling of sleepiness that occurs in MS. Modafinil (Provigil) is a drug used in the treatment of narcolepsy that may also improve the fatigue of some MS patients.

Bladder symptoms: Oxybutynin (Ditropan) and tolterodine (Detrol) are medications that can be used to diminish the sensation of urinary urgency and frequency that frequently occurs as a result of MS.

Available Medications to Treat More Chronic and Progressive Forms of MS
The only treatments proven to work in secondary progressive MS are Betaseron (described above) and mitoxantrone. Mitoxantrone (Novantrone) is a chemotherapeutic agent that has recently been shown to slow progression in secondary progressive MS. It is given intravenously, once every three months. It is given at doses much lower than when used to treat cancer so the side effects are not as severe.

While other treatments have not been proven to work in clinical trials, they have been shown to be useful in anecdotal case reports, so they are sometimes used. This is an area that is very controversial and really depends upon your doctor's philosophy, since they are not clinically proven treatments. This type of treatment includes monthly intravenous steroids, intravenous immunoglobulin, and plasmapheresis (plasma exchange). The last two are generally done in the hospital. Other chemotherapeutic agents, methotrexate and azathioprine (Imuran) are occasionally used in secondary progressive MS.

Again, these drugs are not proven to work, but there have been anecdotal reports of them being beneficial, so if the benefits appear to outweigh the risks, your doctor might suggest that you try one of them.

How do You Get Involved in a Clinical Trial?
During a clinical trial you are closely monitored with neurologic exams and MRIs. In addition, your care during the study is often paid for by the company that is developing the drug. Finally, you get first crack at a medication that may work in MS. There are some drawbacks. First off, depending on the design of the trial, you might be placed on a placebo. There is often a fairly extensive time commitment, as well.

In order to participate, you can contact your nearest MS Center. You may also want to contact your local National MS Society chapter, as they are kept up-to-date with the latest clinical trials that are being conducted.

Conclusion
It is clear that the scope of MS treatment has changed dramatically over the past decade. We now have drugs available to alter the course of MS as well as better medications to treat the associated symptoms. While none of the medications are perfect, they serve as a bridge to the next generation of therapies. By the same token, it is important to remember that MS is a very variable illness, and the decision you make regarding treatment should be an individualized one that you discuss with your physician.