Great MS Debate: In our current health environment, what factors matter most when making decisions?

Welcome to the Great MS Debate.

DR. LUBLIN: Hello. This program will be a debate and reflective discussion with current treatment paradigms in multiple sclerosis, the potential role of the early high-efficacy therapy and outpatient preferences come into the play in the shared decision-making process.

DR LUBLIN: We agree that continued communication between the healthcare provider and the patient seems to be a crucial step that can help inform the patient, so that the patient can participate in the treatment decisions, which will ultimately lead to the better treatment adherence and satisfaction.

So let's shift our conversation from the general concern to patients and providers to specifically how these concerns have evolved in light of the COVID-19 pandemic that has changed dramatically the current health environment.

We're all thinking about risks posed to patients with MS and how to minimize those risks while making treatment decisions. Since there are now growing concerns about keeping MS patients healthy, how have strategies and conversations between clinicians and patients changed? What are the factors that matter the most for treatment decisions?

Let's start with Claire Riley. What are your thoughts?

DR. RILEY: Well, we've certainly had a lot of conversations with patients about their individual risk. And I think their MS and their MS therapy is just part of that. I think, you know, part of my job has been to learn about COVID kind of altogether, because I think a lot of patients view us as, you know, certainly the care provider that they're closest to. So I found myself wearing some different hats in these last several weeks.

But, you know, first I think about age, comorbidities. These some of the same problems, you know, comorbidities that probably make MS worse. So it's an opportunity to talk to your patients about managing their, their vascular comorbidities and such. So I think that's sort thing one to consider.

And then I try to, you know, get a good sense of what is happening with that person's MS. Is this is somebody with stable disease? Progressive MS? Were they very, very active prior to whatever treatment they've been on, and then think about -- you know, because I think they're all or most of my patients anyway are asking, do I stay on my treatment, should I stop, should I decrease my dose, should I extend the interval between infusions, should I take that next course of pills or infusions and those are the questions.

So one issue there is some therapies are associated with some rebound disease activity when discontinued. So I think we certainly don't want to induce that. And beyond that, I mean we're sort of in a period of, you know, less information. We know that there are issues around immune activation and exuberant immune response in the severe ARDS complications of COVID pneumonia and it's possible that, you know, that maybe some of our therapies might help to mitigate that sort of cytokine storm. But this is all hypothesis. And so, you know, I think taking into account where the patient is in his or her MS course is important as we consider, you know, whether to make any modifications.

DR. LUBLIN: So as we were doing before, these highlights that treatment decisions should be made on individual basis, taking into account the factors that you mentioned. While thinking specifically about concerns surrounding COVID- 19, what are our greatest concerns right now when managing MS patients?

Amit?

DR. BAR-OR: So Claire very nicely outlined many of the considerations that when one thinks of the factors in the context of the COVID-19 MS management, some of the main ones can be grouped into these three key areas. The first being the concern as mentioned, possible immunosuppression. The other has to do with the reinfection or the capacity to mount vaccine responses if you are on DMT, and the other is minimizing risk of course of the general viral exposure.

Now, it's interesting the new suppression which I will delve into a little bit is a curious one and our thinking has evolved.

On one hand, we do know that people with MS are at a slightly higher risk of infection related healthcare utilization than the general population, and we certainly do know that some of the immune suppressive DMTs are associated with increased risk of infections.

The interesting consideration is that while obviously natural to consider the risks of immune suppressed patients in the face of COVID, and the questions of whether patients with MS are more predisposed to getting a symptomatic infection with the SARS-CoV-2 virus or the more serious complications of COVID- 19, the ICU, the ventilation requiring, the potential risk of mortality. There is an interesting relatively recent study by a UK group that raises the interesting question that Claire alluded to, of whether immune suppressive therapies may in certain context actually improve COVID-19 outcomes. And this study in the UK looked at over 2,000 patients admitted to the intensive care unit setting with severe COVID- 19. And they asked how many, what proportion of them were on an immune compromised background. It turned out to be just over 2 percent. They then used the historical control cohort of patients admitted to the similar ICU setting of the previous two years with viral pneumonias and they found that amongst them the frequency of individuals who had immune comprised background was 8.5, so almost a four-fold difference, suggesting, according to this data, that being is immune compromised was actually potentially protective of developing the serious COVID-19 related complications.

This study of course is imperfect and should not be over-interpreted, but it's interesting that emerging information from our community is indeed suggesting that patients with MS are not particularly at high risk of either getting symptomatic infection with the SARS-Cov-2 virus or of the severe complications, including those who are DMT therapies. And this is, Claire alluded to, may actually make sense. We now understand that these severe only complication of Covid-19 are not actually the virus itself are going rampant in the face of an insufficient immune system but actually complications of an overactive immune system response to the virus where the person's own immune system is actually contributing to tissue injury and indeed there are several ongoing clinical trials, with therapies including to the ones we used to treat MS that be being assessed for their ability to limit the development of these very severe complications.

So with that in mind, the general recommendation had and continues to be that people on MS DMTs, for the most part, will continue on MS DMTs, the notion that the benefit of continuing would be thought to outweigh the risk of stopping the MS therapy. And while it's true for most patients, certainly there are those in whom the threshold for stopping would be lower. People who may be older, may have comorbidities, or those who have MS profile where the therapy may be less likely to providing significant benefit and stopping or delaying the treatment may be warranted.

The other consideration of course is that MS DMTs may limit the person's immune systems to mount an effective vaccine response. And there it should be noted that even though vaccine responses can be attenuated on a number of the MS DMTs, many people on those DMTs can still mount a sufficient protective. So it's not a moot point.

And in some cases assessing a response to vaccines may be helpful, although not always, engaging the level of protection that they have.

And finally, common sense, it's prudent to limit the exposure of people with MS, whether or not on MS DMTs at the various times to encounters that may increase the risk of contracting the virus, including various healthcare settings, and so avoidance and making sure that one is maintaining the usual masking and careful hand washing is the way to go.

DR. LUBLIN: Thanks, Amit.

So these concerns you mentioned certainly highlight what is at the forefront for most clinicians right now, specifically to your last point.

Let's elaborate a little further, what could we do now to minimize viral exposure risk in our patients?

And Jamie?

DR. STANKIEWICZ:

So these are really practical considerations. We have to think about what sort of interventions were we most commonly doing with our MS patients. And those things really are seeing patients in clinic, doing MRIs, giving infusions, and drawing lab tests. And so I think it's always with so much of medicine benefit/risk, and considering for each of these things how risky is it for the patient, and how much benefit does the patient get from doing these things.

So, in general, I would say given where we're at in the pandemic, broadly, and I guess I would note that everyone here is on the East Coast where there have been sort of higher spikes I think employing telemedicine. I know that our clinic is, with a few exceptions, seeing all patients through telemedicine. Also MRIs, considering whether or not we really need to do the MRI or whether or not it could be delayed. Lab monitoring, same principle, whether or not this is something that can be delayed for a few months, when the situation is potentially under better control.

And I think the other pieces is an education piece for patients, especially around getting blood draws or having MRI and having infusions, and that it's a safe place in the hospital actually that, you know, protective equipment is being used and the patient also will be placed in a mask and there is a lot of cleaning going on, and reassuring people so that there are willing to have the things that as clinicians that we think they should have.

DR. LUBLIN: Thanks, Jamie. In these uncertain times when knowledge about the impact of COVID-19 on patients with MS is limited, it's good to keep in mind what we can do to keep them healthy.