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									NATIONAL MULTIPLE SCLEROSIS SOCIETY MS LEARN ONLINE INTERNET PROGRAM MS TREATMENT OPTIONS MAKING IT WORK FOR YOU >>Welcome, and thank you for joining the National Multiple Sclerosis Society’s MS Learn Online Internet program. I am Rick Turner, your host and medical correspondent. Although there is still no cure for MS, there are various strategies available to modify the disease course, treat exacerbations, manage the symptoms, and improve function and safety. In combination, these treatments enhance the quality of life for people living with MS. Today in our final web cast of this three-part series, we welcome back Dr. James Bowen. Dr. Bowen is the Medical Director for the MS Center at Evergreen Health Care in Kirkland, Washington. Nice to have you back with us, Dr. Bowen. >>Dr. Bowen: Thanks. I am pleased to join you. >>Rick Turner: That is great. Today’s program title includes the words making it work for you, and one way to make disease modifying agents work for you is to try and manage any of the potential side effects, some of which you touched on in an earlier program. Dr. Bowen, walk us through, if you will, the side effects of each of the agents and are there any helpful strategies for managing them? >>Dr. Bowen: Let me start with the interferons. The interferons--the biggest side effects are flu-like side effects, and by this we mean aching and fevers, like when you have the flu. These usually start about an hour after the injection and they last for several hours, sometimes into the next day. This side effect can be minimized with a couple of strategies. One is to start at a low dose, so we often patients at about a quarter dose, and then we increase the amount that they are given as they tolerate it. So when they get adjusted to a quarter dose, then we move up to half dose, for example. Another strategy is to use over-the-counter analgesics. This would be ibuprofen, aspirin, or Tylenol. Of these, ibuprofen seems to work a bit better, though the others also work, as well. This can be taken right at the time that the injection is since the side effect of flu is not going to hit for about an hour anyway. Some patients may need to take the ibuprofen the following day as well if

their symptoms linger. Another thing is that a lot of these patients take their injections at bedtime so that they can sleep through the bulk of it. In addition to that flu-like side effect, there are a few others. One is that we need to follow blood counts. This is to make sure the white blood count and the liver tests remain in the normal range, and there is some question about depression and whether depression may be worsened by interferons, though the data supporting that is fairly week. Another medicine is Copaxone. That one has fewer side effects with injection site reactions being the main one. This would be a red spot at the site of the injection. This can be minimized by rotating the site so that you are not picking on any one site every day. Another side effect with Copaxone is called the systemic reaction. We are not entirely sure what causes this, but one theory is that it happens when the drug is accidently injected intravenously and that the patient then gets a rush from the intravenous injection. Unfortunately this rush is not pleasant. It feels like a heart attack, so patients get chest pain, shortness of breath, a lot of anxiety. It happens immediately within a minute or so of the injection. The most important thing on managing that side effect is just educating the patient that it could happen. If it does, the patient does not need to do anything. They can simply go lie down. It generally passes in 15 to 20 minutes. The other medicines are Tysabri and mitoxantrone or Novantrone. Tysabri has few side effects. It is injected in an infusion center. There is less than 1% of patients that get wheezing from it, which would be an allergic reaction where it makes them wheeze when they breathe. This is treated right at the time in the infusion center and generally passes rather quickly. The more concerning side effect of Tysabri is something called PML, progressive multifocal leukoencephalopathy, which is a virus infection that is quite serious and, in fact, can be fatal. This has been found in 1 in 1000 cases receiving Tysabri. Because of this, there is a tracking system in place called the TOUCH program where patients are followed to assure that they are not being lost to followup and that all new symptoms are being evaluated to make sure they do not represent this infection. In addition to that, we have Novantrone. Novantrone is a chemotherapy medicine. The most complicated side effect of that drug is that it can cause heart damage, and

we monitor that by doing echocardiograms before each dose. The drug is given every three months, so this means patients would get echocardiograms every three months. This involves really an ultrasound of the heart, so it is a fairly quick and painless test. In addition, there is some mild nausea, some hair loss on this medicine. There are medicines we give for the nausea, but generally that is a fairly mild problem and does not require much extra treatment in what we normally do for all our patients. We also have to watch for infections for a couple of weeks, and we manage that by simply making sure the patients are not infected when we give them the drug. This means that we check their blood counts and their urine before we give the drug, and then we have really very few bladder infections or pneumonias within that two-week period as a result of us prescreening the patients. So, those are the major side effects that we have to address. In addition there are a couple of others with Novantrone to simply be aware of. One is that virtually all women stop having menstrual periods when they get the drug, and a small percent of them do not get their periods back afterwards. This would mean that they are infertile. Fortunately, young women tend to do fairly well in this regard and the permanent loss of menstrual cycles occurs mostly in those who are in their late 30s and into their 40s. Another consideration with Novantrone is that there is a potential risk of leukemia. This is still being worked out. The current estimates are that it is about ¼ of 1%. This rate is so low that it is not entirely clear whether this rate is higher than the normal population, but it is something that we watch for in our patients just as a precaution. >>Rick Turner: So, Dr. Bowen, it sounds like overall, while annoying, most of these side effects can be successfully managed. Would you agree? >>Dr. Bowen: Yes, I would agree, and in fact, experienced MS centers generally have very few patients that are unable to tolerate these medicines. >>Rick Turner: So then, are there times when these side effects really are unmanageable and perhaps the best choice is to stop taking the agent, switch to something else? When and how do you make that call? >>Dr. Bowen: A lot of the call is made by the patient, so it is important if patients are having intolerable side effects that they let their doctors know about it and then

we generally know several tricks to help them manage. There are patients that simply none of our tricks work, and the side effect is not tolerable, and then in those cases we fairly quickly move on to another medicine that would have a different side effect profile. >>Rick Turner: Back to a couple of the side effects you mentioned earlier, Dr. Bowen, including things like derepression, elevated liver enzymes, low white blood cell counts, these sorts of things, are there specific signs or tests that people should be aware of to diagnose these issues? >>Dr. Bowen: On the liver and the white blood cell, generally there are not any symptoms that the patient would be aware of with that. If the white blood count went extremely low, then patients could get an infection, or if the liver tests were extremely out of line then the patient might get jaundiced where they turn yellow, but really, we do not see that with these drugs. I think that is because we monitor them with blood work, so the early changes will show up on the blood work. If they are found, generally it simply requires a change in the dose where we just reduce the dose and then the blood counts go back towards normal. For depression, of course, there is no good test for depression. It really is more that the patient needs to alert their health care provider that they are having a worsening of depression so that it can be treated if necessary. >>Rick Turner: What about MRIs, that familiar diagnostic tool, how necessary are they when the patient is on a disease modifying agent? >>Dr. Bowen: I think that we are coming to rely on MRI more and more as time goes on with managing our MS patients. The main advantage of MRI is that for every attack that a patient is aware of there are approximately 10 silent ones on MRI. So, it gives us an opportunity to pick up the silent test and really serve sort of as an early warning system. There is no consensus in the field about how often MRIs should be done, but most people get MRIs about every one to three years after a patient has started a medicine for MS. A lot of people do the first MRI at about a year, and if the activity on MRI has been fairly quiet over that year, then they switch to every one to three years following that. >>Rick Turner: It is wonderful to be in an age when people with MS do have options for treatment; however, I know that a lot of people out there are curious about when some of these options might be administered orally instead of always confronting the needle. Any news on that front?

>>Dr. Bowen: The last time I updated my lecture slides on this there were 72 drugs that are currently in human studies for MS. So, it is very exciting times in MS research world. Out of these drugs, there are about half a dozen that are oral, and, of course, the patients and the researchers are very excited about these because it certainly would be more convenient if we had an oral form. Four of the oral ones that are heading into major studies are fingolimod, which was known as FTY720 until recently, oral cladribine, linomide, and oral fumarate. All of these are going into studies now, and unfortunately it will take about three years for those studies to be completed, so I think that oral drugs are on the horizon but they are probably about three years out at this point. >>Rick Turner: Okay, we will stay tuned. Well, we are just about out of time today. Dr. James Bowen, again I want to thank you very much for being with us for this series on MS treatment options. It has been very informative, and we do appreciate your time and your expertise. >>Dr. Bowen: Thank you. >>Rick Turner: The National MS Society is proud to be a source of information for you about multiple sclerosis. Our comments are based on professional advice, published experience, and expert opinion, but do not represent individual therapeutic recommendation or prescription. For specific information and advice consult a qualified physician. If you have a question that was not addressed, please e-mail us at If you would like more information on multiple sclerosis, click on the resources link on your screen or call the chapter nearest you for an answer to your question. You can reach your chapter by calling 1-800-FIGHTMS. That is 1-800-344-4867. You may also want to check the National MS Society’s web site where you will find more information about today’s topic and a menu of other web casts available to participate in. Funding for this program was provided as an unrestricted educational grant from these National MS Society chapters. For the National Multiple Sclerosis Society I am Rick Turner wishing you health and happiness.

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