Treatments

I plan to put links in this soon, so you can skip right to the topic you are interested in. But for now, it is a long list of questions and answers, so you have to scroll through it to find what you are interested in.

Introductory comments:
Disease modifying versus symptomatic treatments: The treatments I will focus on in this section are the "disease-modifying treatments" which are intended to change the course of the disease. These treatments are supposed to affect the disease process itself and to do things like prevent relapses and stop the accumulation of disability. There are also a lot of "symptomatic" treatments which are aimed at relieving particular symptoms. These include medicines to help with fatigue, stiffness, bladder control, or pain. Symptomatic treatments are quite helpful and make many people's lives better, but they don't affect the disease itself.
Evidence based medicine: Many physicians today try to practice what is known as "evidence-based medicine". This means that we want to use treatments which have been rigorously tested and are proven to be effective. And when new evidence becomes available, we change what we do to take the new information into account. We try to avoid doing something just because that's the way we have always done it, or because we think it should help. A lot of treatments based on "tradition" or "expert opinion" have later been demonstrated to be harmful rather than helpful. Evidence-based medicine is a good ideal or goal at the moment, but only partially practial.  There are many situations where no evidence is available and some situations where the available evidence is inconsistent. But for MS, there are a large number of studies which guide treatment in many situations.
Testing treatments in MS: Testing whether a particular treatment works in MS requires a lot of work. The disease varies a lot from person to person, and a lot even in the same person at different times. Because of this variability, the only way to test new treatments is to use them in large groups of people over a long time. Part of the group will be on the treatment to be tested, and the rest of the group will either be on no treatment (placebo) or a comparison treatment. You then compare how the treated group did compared to the untreated group. Most studies of new treatments in MS require several hundred patients to be treated for 2 to 3 years. Needless to say, this is very expensive, but it is necessary to know whether a new drug works for MS.
Quackery in MS: The unpredictable nature of MS makes it a natural target for quack treatments. Someone is getting worse, tries an ineffective treatment, and gets better. They were going to get better anyway, but they think that the treatment worked, and they tell all their friends about it. The word spreads among MS patients unsatisfied with the effectiveness of their current treatment, and soon another treatment fad has started. The fact that the medical establishment either doesn't know about the treatment or scoffs at it only adds to the attraction. With time, the fad becomes old news, and a new one replaces it. Be skeptical about any new treatment which has not been carefully evaluated and compared to either no treatment or an existing treatment. Don't spend lots of money pursuing things that aren't likely to be helpful.
The influence of money: The current available disease-modifying treatments for multiple sclerosis are all given by injection, and are expensive ($1200/month). Once people start on one of these, they typically stay on the same drug for several years. There are four different companies selling drugs which are similar in effectiveness and all of them have a huge financial incentive to get physicians and patients to use their drug first. The result is a muscular marketing effort directed both at patients and physicians. When you read something about MS or go to a talk about MS, take into account who is paying for it.
In the interest of full disclosure, no-one is paying for this website.  The opinions here are mine alone, and do not particularly favor any particular company.  My job is taking care of MS patients and doing research on MS, not selling a particular medicine. But like just about everyone in the field, I have some ties to various companies. I have given talks which were sponsored by Serono (they make Rebif) and Teva (they make Copaxone). Serono and Teva have sponsored some of my research. I have attended consultant meetings for Serono, Teva, and Bayer (they make Betaseron). I have done very little with Biogen IDEC (makers of Avonex and Tysabri) because I haven't been a big fan of Avonex for reasons discussed below.

Treatment of acute exacerbations
Corticosteroids Corticosteroids in one form or another have been used for treating acute MS relapses for at least 30 years. Corticosteroids are normally made in the adrenal cortex, and have several effects in the body. We use them because they suppress inflammation. Corticosteroids are not the same as the anabolic steroids abused by athletes, nor are they the same as the steroid hormones, testosterone and estrogen.
How soon do I need to treat and exacerbation? Exacerbations or relapses usually develop over a few days. Corticosteroids suppress the active inflammation which is there during an exacerbation, and should be used within the first week or two after the onset of symptoms. If the symptoms have been stable for a while or are already improving, the inflammation is probably gone already and the steroids won't help much.  I advise people to call when new symptoms have been there for 48 hours, and get the steroids started in the first week.
What's the dose? Studies have shown that for MS relapses you need to treat with high doses of corticosteroids. The typical treatment is methylprednisolone 500 or 1000 mg a day for 5 days. Lower doses used for treating other conditions, such as prednisone 60 mg a day, have not been effective.
How are corticosteroids given? For the last 20 years or so, we have usually given them intravenously, either in the hospital or by home iv. But oral corticosteroids are well absorbed, and don't have any worse side effects than iv steroids. The problem with giving steroids orally is that they are not formulated to give the high doses we need. To get the same dose with pills, you end up taking 32 tablets a day. To get around this, I have started taking the 1000 mg vials we use for iv dosing and having the patient dilute them in a glass of juice and drinking it once a day. This works pretty well, but the only pharmacy in the area that routinely stocks the iv vials is the one downstairs in our clinic building.  So I usually give corticosteroids orally, but sometimes still use the intravenous route.
What is the benefit of corticosteroids? MS relapses get better more quickly with corticosteroids. Often, there will be noticeable improvement by the end of the 5 day course. Sometimes improvement starts after a week or so. Most relapses improve spontaneously with time, but recovery is faster with corticosteroids.  Steroids don't seem to affect how much recovery occurs, or how long it is until the next relapse, so the benefit is mainly short-term with a quicker recovery. If you have symptoms which are keeping you from your usual activities, treatment is worthwhile.
Should all relapses be treated with corticosteroids? I recommend treatment only if the symptoms are affecting your usual activities.
What are the side effects of corticosteroids? The usual side effects are insomnia, mood changes, fluid retention, a metallic taste in the mouth, and increased appetite. Corticosteroids are activating, which makes some people feel energetic and happy, while others feel restless and jittery. Rare side effects include more severe psychiatric problems and bone problems. These symptoms typically go away in a week or two after treatment is finished. Longer treatment with corticosteroids has a lot more associated problems, including bone thinning, weight gain, and suppression of the immune system, but these are not usually an issue with the brief courses we use for MS.

Disease-modifying treatments for relapsing remitting MS:
Interferons (Betaseron, Rebif, and Avonex) Interferons were the first medicine shown to affect the course of MS. They decrease the relapse rate by about 30%, decrease the disease activity on MRI scans by about 90%, and may reduce the accumulation of disability over the long term. Interferon is a protein your body makes naturally in response to infections, and it has a lot of effects on the immune system. Side effects from interferon include flu-like symptoms, injection site reactions, and effects on liver function and blood counts. The flu-like symptoms are typically worst at the start of treatment and get more tolerable with time.
There are three interferons currently on the market. Betaseron is given by subcutaneous injection (under the skin) every other day, Avonex is given by injection into the muscle once a week, and Rebif is given by subcutaneous injection three times a week. Betaseron and Rebif are a higher weekly dose than Avonex. Two different studies directly comparing Avonex to high dose interferon showed that the higher dose was more effective.
Glatiramer acetate (Copaxone) Glatiramer is a mixture of synthetic protein molecules which was originally intended to mimic one of the major proteins in myelin. The idea was that regularly injecting this protein would desensitize the immune system. It is not clear how it works, but treatment with glatiramer decreases the relapse rate by about 30%, and may also have a benefit on accumulation of disability. It is given by daily subcutaneous injection. Side effects are usually limited to minor injection site reactions. There is also a rare post-injection reaction consisting of various combinations of chest tightness or pain, rapid or strong heart beats, shortness of breath, sweating, feeling faint, etc. This resolves on its own after about 5 minutes.
Which medicine is best? Based on effectiveness, there is not a clear first choice. High-dose interferon or glatiramer seem to be similar in their effect on relapse rate. The limited direct comparisons of these medicines don't demonstrate consistent superiority for any of the three. There are some studies directly comparing glatiramer and interferon which are in progress, so this may change. I think that there is good evidence that the high dose interferons are more effective than low dose, so I rarely use Avonex.
When should I start treatment? These treatments can prevent some relapses, but they do nothing for problems that are already there. They are better used early rather than late. My approach is to start treatment as soon as I am sure someone has relapsing-remitting multiple sclerosis and that they will likely benefit from the treatment. As discussed earlier, to make the diagnosis, you need multiple episodes. In practice, this usually means that someone has had a first relapse with some type of symptoms and white matter lesions on their MRI. I repeat MRIs at 3 to 6 month intervals, and start treatment either when there are new lesions on MRI or new symptoms.
Many physicians recommend starting treatment without waiting for a second episode. I disagree with this because you would end up treating some people who don't have MS and some people with mild MS who won't benefit. The interest of the drug companies in pushing early treatment should be obvious.
When should I think about switching treatments? There are no clear guidelines on when to consider a change in treatment. These treatments are only partially effective; they decrease relapses, but do not completely prevent them. You will have new symptoms whether you are treated or not. I consider changing treatments if someone has more than one relapse per year.
How long should I be on treatment? There is no definite stopping point. We now have patients who have been on interferon or glatiramer for more than 10 years. The medicines don't seem to lose their effectiveness over time.
More aggressive treatments--Natalizumab (Tysabri) Natalizumab is a treatment which interferes with the movement of white blood cells around the body. Normally your immune cells patrol the body, circulating in the blood, crossing the blood vessel wall into the tissues, including the brain, moving from tissues to lymph nodes, and then back into the blood. Natalizumab blocks the movement of white blood cells from the blood into the brain. In the clinical studies, natalizumab decreased the relapse rate by about 70%, which was very exciting. Unfortunately, it also caused two cases of a rare brain infection called PML in MS patients who were both taking interferon at the same time. This infection was fatal in one case and disabling in the other.
Natalizumab is now being marketed for use as monotherapy (not to be combined with other immune suppressing drugs) in relapsing-remitting MS. To receive the drug, you and your physician have to participate in a rigorous surveillance program so that we know if more cases of PML occur. The estimated risk for PML is about 1 in a thousand, and I am currently using it in a small number of patients who were having frequent relapses in spite of treatment with interferon or glatiramer. Future use will depend on how many more PML cases occur.
Natalizumab is given by intravenous infusion every 4 weeks, and is substantially more expensive than existing treatments (about $28,000 per year)
More aggressive treatments--mitoxantrone (Novantrone) Mitoxantrone is a chemotherapy drug which is used to suppress the immune system in people with really active MS. It is given intravenously, sometimes every three months and sometimes once a month. It can stabilize symptoms in active disease. Short term side effects are mild nausea, hair thinning, and immune suppression. Potentially severe, but infrequent, long-term side effects are weakening of the heart muscle and leukemia. Treatment is limited to two years to avoid most of the heart problems. I am using this in a few of my patients with active disease.
How about combining treatments? Since the treatments are only partially effective, there has been a lot of interest in combining two different treatments to get a better effect. The problem with doing this is that we don't know for sure how any of the effective treatments work. One of the combined treatments might block the effect of the other, or even worse, the combination might interact in a way that is dangerous. This worst-case scenario, where each treatment alone is beneficial but the combination is dangerous, has been reported at least twice. My practice is to start with a single treatment which I know is effective. If that doesn't work, I try a different single treatment. If that doesn't work, then I start making up combinations, but not many people have MS which is that bad. For now, I wouldn't advise combining treatments unless you are part of an organized study or you have really active MS.
Other options There are numerous other treatments which are used at times in MS, but the evidence that any of them are effective is limited. These include azathioprine, methotrexate, cyclophosphamide, cladribine, IVIg, plasmapheresis, etc. These are sometimes useful when the primary treatments are ineffective.

Treatment for secondary and primary progressive multiple sclerosis
This is a lamentably short section, and we desperately need an effective treatment for progressive MS. Mitoxantrone may have some usefulness in early secondary progressive disease. I often keep my secondary progressive patients on the treatment they were getting while they were relapsing-remitting in the hope that it is still helping. For someone who is progressing rapidly, I will try immunosuppressive treatments, usually without good results.  Most of my progressive patients are on no disease modifying treatment.