You’re listening to NeuroFrontiers on ReachMD, and this episode is sponsored by Novartis. Here’s your host, Dr. Hector Chapa.
Welcome to NeuroFrontiers on ReachMD. I'm Dr. Hector Chapa, and joining me to discuss how we can better manage our efficacy challenged patients with multiple sclerosis, or MS for short, is Dr. Ahmed Obeidat, who is Assistant Professor in the Department of Neurology, and the Founding Director of the Immunology and MS Fellowship Program at the Medical College of Wisconsin. Dr. Obeidat, thanks for joining me today.
Thank you very much for having me.
So let's just dive right in, Dr. Obeidat. What do you consider when selecting the therapy for patients with MS?
Well, I consider so many factors, and some of these factors can be related to the disease itself. So we look at how the disease activity is it really very highly active? Is it moderately active? Or is it a mild activity? But also we look at patient factors. So when we select treatment, we want to understand, what are the patient preferences that can we take into account when we select a medication. For example, our patients may prefer certain type of administration of medicine, certain frequency, and then if that fits with what we think would be a best, approach for their treatment, then we take those factors, of course, into consideration and into our selection. And again, it's always a shared decision making between us and our patients. And as we think about these factors of efficacy, of course, comes into play as we want to make sure that the medication that we select will have efficacy against their disease.
And speaking of efficacy, once a patient does begin therapy, how do you assess their response to treatment?
Yeah, so several ways that we can assess response to treatment. And we can divide those ways into factors or treatment response related to the disease itself, but also factors related to the individual who’s taking the medicine. So we can also have these shared factors, right? So when we think about factors related to measuring efficacy, we have biomarkers that we can measure, and mainly, including the MRI.
So the MRI is a very important part of how do we follow whether the medication is working for MS. For example, we always look to see if there are development of new, enlarging, or contrast-enhancing lesions in the brain or spinal cord. So if we see some of those that may mean that there is a little bit of suboptimal efficacy. You know, medications vary in their ability to stop these types of changes on MRI, and some may do it better than others in trials. But also, for certain patients, some may do it better than others for a certain patient. So we can measure efficacy by looking at MRI disease activity.
But also we can measure efficacy by asking the patient, are they having relapses? Are they having worsening of their disease? And also, are they progressing? You know, are they having, you know, difficulty in maintaining things that they used to be able to do?
I often make sure that, you know, the patient themselves are telling me, do they think that the medication is working for them? And of course, I support this by, you know, our also measures of disease activity. Sometimes what we do is we actually also ask, ‘How is the journey with the medicine?’ Are they, you know, tolerating it okay? Are they having side effects? Right? If they're having some of those, even though the efficacy is working well, we tend sometimes to discuss the possibility of switching medication or changing, because we want our patients to really have the best possible experience with their treatment.
So you mentioned something that I want to readdress here for our audience because it's important. So just as a quick follow-up, Dr. Obeidat, could you again go over the quick signs that somebody may be an efficacy challenged patient?
Yeah. So if we look at it from an overall perspective and what general signs are they may be happening more frequent, happening of relapses, which is defined as new neurological symptoms that can last for 24 hours or more without the presence of an external factor like an infection, fatigue like stress or other factors that can make symptoms of MS appear worse. So relapse is one.
Second, activity on MRI beyond what we can accept. Some people may argue we don't accept any MRI activity when we try treatment. And we aim for something called NEDA, which is no evidence of disease activity. If that's what we're aiming for, then we may, you know, be changing a lot of medications to achieve this. That's a concept that's evolving in MS. It's called no evidence of disease activity, meaning no relapses no MRI, new lesions, or enlarging lesions, or contrast-enhancing lesions, and no disease progression.
We aim for a decrease of number of relapses, decrease in our number of MRI lesions, and decrease in progression. So these are the three items that we look at, the three measures or signs of disease activity.
For those of you just tuning in, you're listening to NeuroFrontiers on ReachMD. I'm Dr. Hector Chapa, and I'm speaking with Dr. Ahmed Obeidat about managing efficacy challenged patients with multiple sclerosis.
So Dr. Obeidat, once you identify an efficacy challenged patient and determine the need to switch therapies, how do you go about switching to a different therapeutic option?
Yeah, so this again, great question and, certainly involves the patient. So when we identify that there may be some suboptimal disease activity control, meaning that maybe there are more relapses than what we'd expect, or new MRI lesions that we feel that maybe the medication is not optimal for the patient, or there is some progression of the disease that we cannot explain by other factors, then we actually asked to meet with the patient. And the patient will often come in to meet with us in the clinic, and then we will discuss this. We will discuss our concerns. The patient may have their own concerns also, say maybe, ‘My disease is getting worse,’ and then we would have a plan. So sometimes, if the patients like the medicine in a way where they're not having difficulty or side effects, and it's fitting well with their lifestyle, I sometimes see hesitancy in, you know, changing the medicine. So what often I do in particular cases like this, where I would say, ‘Okay, well, we saw some new lesions on MRI that indicate diseases active, but how about, you know, but you want to stay on the medicine, but how about we do another MRI in six months? And if this MRI shows more lesions that form, that means we probably need to switch you off the medication.’ So sometimes I take this into consideration because, well, not on medication, they don't have 100 percent ability to stop the disease, right? And we will see some lesions, we will see some relapses. But it's a matter of what do we accept? And what do we don't accept? You know, and when do we see that maybe we can give another chance, you know, we’ll repeat an MRI six months, and if that continues to happen, then we will most likely need to switch.
And often when I select another medicine, switching, I often switch to a medication from a different class, meaning that the medicine works in a different way than the medicine they are on right now. Because if that mechanism failed in a way or is not highly effective for that particular patient, then it's switching within the same class to a different agent, you know, is not going to help.
So these are the things that I consider, again, from an efficacy standpoint we try to go to a different class of medication, if there is a failure of one medicine within a certain class.
Now let's zero in on B cell therapies for just a moment. Which of our efficacy challenge patients may benefit from this kind of therapy?
Okay, the B cell depleting therapies are, you know, some of the therapies that we actually been using now for several years. Those therapies target what we call the B cells, or B lymphocytes. And, they're anti-CD-20, so there are markers on lymphocytes that these drugs can target. And then they’re immune depleting therapies, meaning that they deplete the cells, or the B cells, out. And what happened is we think that by depleting some of these cells, there is ,some improvement of this immune dysregulation that happens in MS, where depleting B cells may actually result in a favorable decrease in inflammatory activity in multiple sclerosis. These medications are considered overall a highly effective medication. So in some of the studies that look at our treatment approaches that are what we call traditional treatment approaches. And there are treatment approaches that are called highly effective or highly aggressive, depends on how they kind of call it in those studies. And the B cell depleting therapies are among those highly effective therapies. And this is from data from clinical trials, where they showed superiority, to some other competitor medications or medication that the active competitor, I would call it during the study.
So when we think about B cell depleting therapies, in general, we try to talk to our patients about their effectiveness, about the results of clinical trials depending on what piece of the treating therapy we're talking about. And then we try to talk to them about what are the potential concerns or risks associated with these therapies, and to try to mitigate those risks.
So Dr. Obeidat, once you identify an efficacy challenged patient, and determine the need to switch therapies, how do you go about selecting a different treatment option?
Yeah, thank you very much for this question. So typically, when we identify that there may be, you know, some suboptimal response to a medication we meet with the patient, and we talk about this issue, we talk about whether this was a failure from a relapsing standpoint, whether this is a failure from having new MRI lesions or more than what we had expected, or there is ongoing disease progression. So we talk about why you were, you know, kind of saying this may be not optimal anymore, and we need maybe to switch treatment. And then we hear patient input into this. Do they think that they're doing okay? Do they think that they're maybe getting worse from the MS standpoint? Or whether they're very concerned about, you know, the new disease activity on MRI.
And we talk about, you know, what would be our best approach to mitigate this and change this? And we'll talk about something that we call switching therapy. And switching therapy can often be to a medication from a different class that treats multiple sclerosis.
But I think switching therapy can happen and you know, if we are aiming to something like NEDA, or no evidence of disease activity, and and then patients are having relapses or having new lesions or having progression, then definitely switching is a consideration. And again, we take into consideration the same thing, patient factors, disease factors, and a different class of medications, switching of the class. That's how I would approach switching for efficacy reasons.
Lastly, Dr. Obeidat, I'd like to open up the floor to you. Do you have any final thoughts on how we can better manage our efficacy challenged patients with MS?
Yes, so thank you for this question. And I think, you know one of the important factors that we should be considering is identifying the patients who are efficacy challenged by treatments of MS. And identifying these patients, you know, require education early on, which requires us to talk to the patients first, and, you know, kind of help them understand when is the time for them to call us and say, ‘Well, I'm having maybe a new relapse,’ or maybe, you know, ‘I may be progressing more in my disease.’ And then also kind of look into doing more MRIs on a routine basis.
So what we do is we often do, you know routine MRIs, uh, that they're not triggered by relapse, they’re not triggered by, you know, any complaint from the patient, it's mostly routine MRIs, trying to do surveillance, trying to detect the formation of new lesions or contrast-enhancing lesions in the brain. So that may identify a suboptimal efficacy for the treatment they're on.
So if we're able to identify who are the patients who are challenged by, you know, efficacy challenged, we're able to perform the switch, we're able to switch classes of medication, we're able to offer them the help they need.
And you know, very importantly, is to have an open dialogue with our patients, right? We have our teams of, you know, nurses, clinical pharmacists and then our team overall, in general, kind of have a connection with our patients. We are accessible to our patients. With the advent of the electronic medical records, patients can ask us questions any time. They can report for us relapses, they can send us messages, they can, of course, call us. But also we can respond to those requests, and make sure that we're identifying patients who may be failing their treatment. And we want to make sure that we are able toact on promptly and early on, I would say, to be able to give the most possible or the most you know, effective way of managing their disease to achieve the best possible outcome.
So these are things that we can consider. And I think identifying the patient and then explaining why we want to do a switch of the treatment, and then explaining what would be the options. What are the other options to switch, whether we're escalating therapy, whether we're going a different class, or sometimes whether we're staying within the same class, if this switch was for a different reason. But most of the time for efficacy, we switch away from the class of medication that they're being treated with. You know, again, with efficacy issues if we see that there are some progression of symptoms, some worsening of some of the MS-related difficulties, we can always also involve the multidisciplinary care model where we can ask our patients to or connect our patients to our colleagues and various departments to give them the best possible care in relation to MS.
Again, it's all centered around the patient. And our goal is always to achieve the best success for our patients in their journey.
Great insights. And with those remarks, Dr. Obeidat, we come to the end of our program. I want to thank you for joining me today. It was great speaking with you, Dr. Obeidat.
Thank you very much. Thank you very much for having me. Enjoyed talking to you. Thanks.
This episode of NeuroFrontiers was sponsored by Novartis. To access other episodes in this series, visit reachmd.com/neurofrontiers, where you can Be Part of the Knowledge. Thanks for listening!