COLLEEN MILLER, RN: My name is Dr. Colleen Miller. I'm a Nurse Practitioner at the Jacobs Neurological Institute and the Baird (?) MS Research Center. I welcome you all back for another conversation, and I thank the sponsors for inviting me once again.

Joining us tonight, I have two of my colleagues that have quite an extensive MS background in MS clinical care and research. First I would like Amy Perrin Ross to say hello, give you a little synopsis of her background and then we will introduce Jan Shilling.

S: Hello everybody.

AMY PERRIN ROSS, RN: Thank you Colleen. Hello everybody. Hi, this is Amy Perrin Ross. I am an advance practice nurse at Loyola University Medical Center in Maywood, Illinois, which is just outside of Chicago. I have been working in MS for about 20 years, and in my role as Program Coordinator, I coordinate both the MS center, as well as the Alzheimer's Center and run the clinical drug trials. And Jan?

S: Thanks. I'm Jan Shilling from the University of Washington Medical Center in Seattle, Washington. I am a registered nurse and work at the Western MS Center as the Multiple Sclerosis clinical nurse. I have been involved in MS nursing now for over 10 years and am responsible for all of the nursing patient care and coordination of patient care within the Western Multiple Sclerosis Center.

COLLEEN MILLER, RN: Thank you so much Jan. I guess I should give you a little bit more information for those of you that have not tuned into previous conversations that I have been involved in. I am a nurse practitioner at the Baird MS Research Center and the Jacobs Neurological Institute. I have been there for over 12 years, both as a nurse practitioner and a clinical nurse specialist.

I carry a degree as a doctorate of nursing science, which allows me to do further nursing research. I have been very involved in clinical care and clinical trials over my years.

I thank you so much for joining us. Our purpose tonight is to discuss long-term therapy issues that MS nurses deal with on a regular basis. Hopefully, we can share some of the expertise of the speakers here and help you deal with some of the challenging issues for MS nurses.

What's going to happen this evening is we're going to address certain issues, such as the natural history of MS and how it has changed with the new disease-modifying medications. We're going to be talking about reasonable expectations of patients and how to help our patients come to understand what that is. We're going to talk about side effect management and specifics on helping our patients tolerate these medications and stay on treatment. We'll also discuss some symptom management and certainly at any point in time, would welcome any input and questions from the audience. Then we're going to talk a little bit about relapses and progression.

Additionally, we're going to address four of the tougher questions in regards to this issue that we deal with on a daily basis. But first, I just wanted to take a step back and talk about the natural history of multiple sclerosis.

Now, as you all know, multiple sclerosis is a demyelinating illness of the central nervous system, including the brain and spinal cord. It usually starts as a relapsing disease, which in about 10 years will render most people to require a walking device or wheelchair or some sort of support for mobilization.

The illness naturally goes - or changes at some point in time to a secondary progressive type phase of the illness where people no longer experience the exacerbations.

I guess I should back up and kind of get us all on the same ballpark as far as what an exacerbation is. When we talk about an exacerbation tonight, what we're talking about is symptoms that are new or worsening that are not related to an infection and that occur consistently for at least 24 hours. So when we're talking about an exacerbation, we're not talking about transient numbness or some blurring of vision when somebody is exercising. And we're not talking about worsening and weakness when we have urinary tract infection. As you all know, that is not an exacerbation. That is the effect of the infection.

So 80% of people with multiple sclerosis start with relapsing disease. They may start with an optic neuritis or a transverse myelitis, which is a lesion in the spinal cord that can cause weakness or numbness in the lower extremities, or one side of the body, bladder problems, etc. Or some brain stem problems such as Bell's palsy, eye movement disorders, etc. Often these will pretty much go away over time, even without help. But these relapses tend to happen up to three times a year, or sometimes a relapse will start and they won't have another symptom for 10 years. It's extremely variable and often unpredictable.

But after the phase of relapse, patients tend to lose these attacks or relapses, or they are not as obvious as they used to be. But then their level of function tends to slowly slip. That is what we're looking at when we look at secondary progressive disease. It's that flipping of function.

Now before the 1990s, there was really nothing much we could do to affect the natural history of multiple sclerosis. Actually, in the 1980s, we used medications such as ACTH and in the late 80s we used high-dose IV steroids, such as methylprednisolone to shorten attacks and return the person to their baseline as close as we could.

But in the 1990s, Betaseron was the first disease-modifying agent introduced. Betaseron is interferon-beta-1B. As you all know, it is a subcutaneous injection taken every other day. It was approved for lessening the relapses of multiple sclerosis and certainly the effect of multiple sclerosis on the MRI scan.

Approximately one year later, Avonex was approved for the treatment of relapsing forms of multiple sclerosis. Now Avonex is interferon-beta-1A. It is a once-a-week intramuscular injection, and Avonex was approved not only for decreasing the number of relapses and its positive effect on diminishing gadolinium-enhancing lesions on the MRI, but it was also approved for slowing the progression of disability for multiple sclerosis. This was a landmark discovery. It gave us hope for people with multiple sclerosis.

Since that time, Copaxone or glatiramer acetate, has been approved for the treatment of relapsing/remitting multiple sclerosis, and it was approved to decrease the number of relapses and the effect on MS.

In the last three years, Rebif, which is interferon-beta-1A given subcutaneously three times a week was approved for decreasing relapses and the effect of the MRI on relapsing multiple sclerosis.

So to sum this all up, before the 1990s, we really had nothing that would effect what would happen to people from their MS in their future. So we knew that if they had a relapsing disease it would probably become progressive and they would steadily get worse.

Well, we can't say that that's the natural history these days because we have changed the whole face of multiple sclerosis. I hope that we have also changed the future for patients with multiple sclerosis and certainly decreased the amount of accumulated disability and hopefully postponed any disability that our patients experience.

But that information is being collected at this point in time, and nobody can - there is no documentation yet saying just how we did that. But the bottom line is that we are affecting the natural history of multiple sclerosis.

When we have patients that are started on a disease-modifying agent, what is reasonable for them to expect from these medications? Amy, maybe you can take this question or explain what a reasonable expectation to the disease modifiers might be.

AMY PERRIN ROSS, RN: Well Colleen, that's a really good question. As I think about reasonable expectations, I think that there are two components to the whole idea of reasonable expectations. Expectations that I as a nurse help the patients set for their therapy and their disease course, but also I have recently been taking a step back and looking at what are reasonable expectations that I should have of the patient who is on one of the disease-modifying therapies? I think it's important to start with that.

The first question that I asked myself is, "Where are these people in the whole grand scheme of their diagnosis?" Have they been diagnosed a week ago? Have they been diagnosed six years ago? Where are they in the understanding of their disease process, the understanding of the natural history? Therefore, how ready are they to even begin therapy let alone even think about staying on therapy? Are they ready to discuss therapy?

Well, most of us who practice MS every day are well aware that the important thing is to get these people started as early as possible. In my experience, sometimes patients are just not ready right off the bat, despite the fact that we want to give them a prescription and get them started, and we do our best to help them understand that.

If they're not ready, they may reluctantly take the prescription and stop shortly after, usually within the first three months. So assessing readiness and seeing what we can do to evaluate where they are at and what some of the limitations may be, I think, is really important, rather than get them started on something that they stop, and they shop around going from doctor to doctor and treatment to treatment.

One of the other questions that I ask myself is, "What are their current limitations?" Have they just recovered from a significant bout of optic neuritis and their vision is definitely much better but perhaps not back to normal yet. Do they have upper extremity weakness? Do they have tremors? Are there things, physical limitations, and/or cognitive limitations that may prevent them from learning the number of complex steps that are required to actually inject themselves on a regular basis.

The third question I often ask and try to get at is, "What are the issues related to family support or lack of family support?" I have patients who have told me that they are ready to start, but their family doesn't really think that this is such a good idea. It's a nuisance. It's an intrusion in their life. I try to help them reframe the whole issue of disease-modifying therapy. Rather than looking at it as yet one more thing to do or an intrusion on their life, I try to help them understand that this is one way that they can take some active control of their disease process. We have data on all of these therapies that look at the effects in terms of relapse or MRI activity and so on.

Moving on to helping the patient set realistic expectations, again, looking at whether these are newly diagnosed patients versus patients who have had the disease for quite some time. The newly diagnosed patients may assume that if we give them a disease-modifying therapy, that they're never going to have a relapse again, that the one they've had is the one and only and that's going to be it. We certainly have to help them understand that none of the disease modifiers is going to prevent a relapse. Ideally, we're going to minimize the impact of the relapses and certainly, perhaps, shorten the duration, but we're not going to prevent relapses all together.

Another one of the misconceptions that some of the people have that have had the disease for a while - maybe this is their third or fourth attack - and they finally decide that it's probably time to get started on some therapy - is that the disease-modifying therapies will make their symptoms better. It will make their vision better. It will strengthen their gait, some of those kinds of things. Certainly we have to, again, help them understand that the disease modifiers really have no impact on their symptoms.

COLLEEN MILLER, RN: You know, Amy, if I can interject in this right here. Even though we tell them this, they don't always want to hear it.

AMY PERRIN ROSS, RN: Right.

COLLEEN MILLER, RN: I have, in some of my research with some of my patients, I have found that they say, "You know, I was told that I wasn't necessarily going to get better, but I expect to get better anyway."

AMY PERRIN ROSS, RN: Right. And on the other hand Colleen, we have people who come and tell us, "Oh my symptoms are so much better. I'm so glad I started this therapy."

COLLEEN MILLER, RN: Right.

AMY PERRIN ROSS, RN: Again, it's fairly important to have them have these realistic expectations because with the next exacerbation, those symptoms may not be a lot better. So you're absolutely right.

One of the other things that everybody wants is a cure. They want these disease modifiers to stop the disease in its track, to cure them of what they've got and not allow them to go on and have any disease in the future. Again, we have to stress the fact that it's not a cure, again, helping them reframe the whole issue of why they are doing the therapy and what we expect from it.

They expect there will be no, if any, relapses, and we also, in terms of looking at realistic expectations, have to help them understand what the potential side effects are. But also rather than just rattling off the list that all of the disease modifiers come with, we need to help them understand that each person with MS is an individual and MS affects each individual differently. So not everybody is going to get flu-like symptoms. Not every is going to get the fever or the fatigue or the malaise. We try to help them manage some of those side effects in the beginning, and Jan will be talking about some of that side effect management in a few minutes.

But if we can help them understand that they don't necessarily get every one of the side effects on the list, and/or for the most part, those side effects with some good aggressive therapy are really very manageable and often are decreased as therapy goes on.

I think those are the key points for helping set realistic expectations for both the patient, as well as the nurse or the healthcare provider.

I think at this point we should let Jan talk to us a little bit about some of the side effect management and symptom management that go into realistic expectations.

COLLEEN MILLER, RN: This all is getting at the need for the patients to stay on these therapies because if they don't stay on their therapies, the therapies can't help them. If they bounce around and change therapies, we're not getting a good therapeutic effect. So the way that we do - nursing does best really to keep people on their therapies is not only to educate them about what these are doing in their bodies, but to help them with the side effects that they may experience. Jan, can you help us with this one?

JAN SHILLING, BSN: Well, I hope so. I just have to reinforce what both Colleen and Amy have just said, that I think that the key nursing components of working with MS patients are one, education. There cannot be enough said about helping patients in that area and providing them with information about multiple sclerosis.

I think nurses are also compelled to help patients improve their general health. There has actually been some information about exercise and self worth, that patients who take control of their own general health and feel more in control and may experience, therefore, a less disabling course of the disease.

Also because MS is so variable, nurses need to really help with an individualized plan of care for each patient, so that it's not a cookbook, if you will, but really meets specific patient needs and addresses all of their issues.

Then finally, disease treatment is a whole spectrum. It is the disease modifiers, as well as the symptom management of the various symptoms that are not necessarily addressed or helped by the disease modifiers.

Side effects, I think, management is one of the key things that nurses get involved with. I think the key things that nurses get involved with. I think the thing that really was a watershed moment was when it occurred to some brilliant person - I wish I could take credit - that we shouldn't start people on a full dose of interferon - all three of them, the Avonex, the Betaseron and the Rebiff, and that people should start out at a lower dose and titrate up, and that by doing that, it really helps to decrease - especially the flu-like symptoms, some of the general malaise, and even some of the fatigue that some patients feel when first initiating the interferons.

Likewise, I think it's important to encourage patients, while we all, I think, have sort of a method of titrating up the medication - or if you don't, you try to think of one - but I think it's important to let the patients know that they should titrate it up as they can tolerate it, so that eventually they will be able to tolerate it, and as Amy mentioned, not feel like after a while that they just can't stand this choice and want to go off of the medication.

COLLEEN MILLER, RN: Jan, that brings up a thought about a patient that I had who got himself up to three-quarters of a dose of Avonex. When he tried to go to a full dose, he was just absolutely overwhelmed. We ended up leaving him on the three-quarter dose for almost three months.

JAN SHILLING, BSN: Exactly.

COLLEEN MILLER, RN: Before he was mentally and physically able to move up to that full dose.

JAN SHILLING, BSN: Exactly. We have even had patients that have gone up to the full dose and then for whatever reason - simply didn't tolerate it very well, and so then were cut back for a period of time, and then gradually increased again. I think that's the patient specificity that nurses need to provide for the MS population and to be able to identify those kinds of situations.

COLLEEN MILLER, RN: Jan, some of the problems that they experience the most that causes them to go back or not to be able to tolerate it, would be what, in your experience?

JAN SHILLING, BSN: I think, again, the flu-like symptoms are some of the key ones. Injection site reactions are also a very large problem for a lot of patients. There are a number of things that can be provided to decrease injection site reactions; pain being one of the reactions. A localized anesthetic, topical cream or something - EMLA was good. Unfortunately, EMLA is not available right now, but there are other topical local anesthetics can be applied. Icing even works to help ice the area first to numb it, though again - or not again - but you don't want to ice for too long because that can create other side effects or problems.

COLLEEN MILLER, RN: You would suggest that somebody ices for what, maybe five minutes?

JAN SHILLING, BSN: About five minutes.

COLLEEN MILLER, RN: Okay.

JAN SHILLING, BSN: Yeah. For about five minutes. And then ice again afterwards if necessary.

I think that rotating injection sites is one of the key things that sometimes patients find that they have a favorite spot and tend to use that spot more to the exclusion of some other ones. Rotating sites can really help, though I have to say that there are many people that just find that, for instance, in Avonex, they just can't imagine having someone give them a shot in their arm, because certainly they can't do it themselves. So for patients who are doing the subcutaneous injections, the thought of injecting into their abdomen. So I think it's okay to have a site that you're not comfortable using, but you need to have multiple other sites that are available that you're comfortable using. That's crucial for the subcutaneous injections.

COLLEEN MILLER, RN: It is.

JAN SHILLING, BSN: It's not so bad with the once-a-week intramuscular injection because there are less side effects, and if the injection is given properly, you don't have to use as many different sites.

That's a very good point.

COLLEEN MILLER, RN: That's a very good point. I wonder if you might share - you know, I'm looking at the clock here and we are just losing time.

JAN SHILLING, BSN: Yes.

COLLEEN MILLER, RN: But I wonder if you might share some pearls in regard to fever and the flu-like symptoms.

JAN SHILLING, BSN: Yes. For the fever, Tylenol or ibuprofen are key. When we initiate therapy for patients on the interferons, we just tell them to take the Tylenol or ibuprofen, whichever they tolerate because some people don't tolerate the gastric effects of the ibuprofen, but either one - before they do the injection and then just take it on a regular basis, whatever is indicated on the particular and nonsteroidal antiinflammatory that they're using, four or six hours, and just use take it on a continual basis for the first several days. Then depending on what they're using, if they're feeling like they may feel okay, they can cut back, but if they feel like, you know, there is still something coming through, keep taking that for a while.

We have patients that have been, for instance, on Avonex, and they still with their weekly injection just take a Tylenol or ibuprofen before they do the injection and have no problems. So I think that that's the key thing for the fever.

Then the flu-like symptoms, again, I think slow titration is probably the key thing. Usually the flu-like symptoms do diminish and completely go away after three to six months. Again, it varies among patients.

COLLEEN MILLER, RN: All right. Jan, that's wonderful, and I thank you very much for helping us with that. I wonder if you might tell us how, as a nurse, you would respond to a patient who says, "Well, why should I take this medication when the side effects are making me feel worse than I was before I was on it?"

JAN SHILLING, BSN: Right. That's a really tough one, and I sure appreciate people feeling that way. But the thing that I like to point out to patients is that while you may be feeling worse, we don't what your disease would be like if you weren't on it at all. They may feel worse, but there is a lot of times not a lot of neurological data that says that their neurological status has changed, which is the key thing that we're trying to maintain at this point.

So a lot of times, what I try to tell patients is that the feeling worse is usually within the first few months of therapy and this initiation and then that should resolve after a period of time to where they have few to no side effects from the disease modifiers.

COLLEEN MILLER, RN: Sometimes I try to put it in a frame of reference that they understand. I will say to them, "You know, it's kind of like birth control. When it's working, you may not feel any different or you may not feel that it's working."

: Right.

COLLEEN MILLER, RN: : But it is working underneath and all you need to do is go off of it, and find out that yes, in fact, it was working.

AMY PERRIN ROSS, RN: You know Colleen, your comment about birth control makes me think about my response when people say to me, "What if I miss an injection? What if I decide I'm going on a weeks' vacation and I just don't want to take that one dose of Avonex with me?" I say to them, "Well, if you stop the medication for whatever reason, it's kind of like stopping the birth control pill. When you're not taking the pill, you're not protected against pregnancy. If you're not taking the injections, you're not protected against the relapses and the MRI activity and whatnot."

So while we sometimes need to allow these people a reasonable break for a week or two, we very often need to think about helping them with their, again, their expectations and realizing that stopping and starting and stopping and starting is not something that they really want to do on a regular basis.

COLLEEN MILLER, RN: That's a wonderful point. Amy, maybe I could ask you to briefly address the question, when a patient says to us, "Why should I stay on this medication if it costs so much and it doesn't make me feel any better?"

AMY PERRIN ROSS, RN: Again, I think your initial comments about the natural history of the disease, Colleen, is what I use to answer those questions for people. Yes indeed, this medication does cost quite a bit. Even with insurance coverage, co-pays can sometimes be pretty big for some of these patients. Again, our key is that the medication is not going to make them feel any better. What we're hoping to do is slow down the progression of the disease.

One of the other things that I often look at when people say things like, "Why am I getting worse," and "Why don't I feel any better," or things of that nature, is that I try to evaluate if we've got any depression going on. As you know, depression is one of the things that is highly associated with MS. It may or may not be associated with the use of interferons. I know there is some controversy about that now.

But the issue is, has the diagnosis really sunk in and are they now to the point where they are experiencing some depression? We certainly don't want to do miss that. We would do a Beck Depression Inventory or some screening for that at that point as well.

JAN SHILLING, BSN: If I can just add, I think the other thing too is that a lot of times people may feel that they are getting worse when they are having other symptoms of MS. For instance, one of the main problems for people with MS is fatigue. Sadly, none of the disease modifiers really address that. People just think, "Well, that's just the disease." But there are many drugs available and interventions that can really help with that, that issue of fatigue.

Likewise, another problem sometimes for patients can be cognitive function. While we feel like we're communicating with the patient, it may be that they're not remembering everything that we have shared with them. I think that sometimes an evaluation of that, along with the evaluation for depression because sometimes it's hard to tease and separate those two out; you know, cognitive -- lack of cognitive functioning versus depression. They are obviously very different, but sometimes people actually also describe fatigue in terms of cognitive function and depression. So those three things, I think, are key to evaluating and helping patients with MS.

COLLEEN MILLER, RN: They absolutely are. We are running out of time here, unfortunately, because this is such a wonderful, informative event.

I want to thank all the people who have tuned in and have listened to us. I especially want to thank my colleagues and friends, Amy Perrin Ross and Jan Shilling.

I would like to thank everybody for joining the MS Conversations, and we hope to be able to provide more services for you in the future. Have a nice evening. Good night.

JAN SHILLING, BSN: Good night.

AMY PERRIN ROSS, RN: Good night.