Treatment Talk: Lifting the Fog on MS Treatments (Episode 3)

Susan Payrovi, MD: Right. This is an exciting time in MS care. There’s so much research exploding into therapies. So today we’re going to talk about some of these mainstays of treatment and all the different options out there. And while they’re wonderful to have, it can be daunting to try to pick a therapy that is a good fit. But before we dig into our conversation and tackle this huge topic, let’s head into our first segment, The Doctor Is In, where I, as a real MS patient, am going to ask our neuroimmunologist, Dr. Mirla here, some very common questions that we see in clinical practice.

Question number one: I’m newly diagnosed. What are some considerations in choosing a therapy, Dr. Avila?

Mirla Avila, MD: That is a great question, Susan, because we have to actually tailor the treatment to the patient. There are many things that we have to take into account: the age, how aggressive is the MS, are there a lot of enhancing lesions or not, is it a male patient, is it a female patient, are there plans to start a family soon or not, and also the ethnicity, because we do know that some ethnic groups can have a more aggressive MS, especially Hispanic and African descent. So there are many things that we have to take into account when we choose a medication.

We have 21 options and counting, so sometimes it can be a little bit difficult, but it’s a good problem to have because we have different options. We have some pills, we have injections, we have infusions. But this is something that has to be taken into account with your neurologist or your prescriber and with your preference, too. And, as I said, the presenting factors in each patient. So it has to be individualized.

Susan Payrovi, MD: Thank you. And I would also ask a question for a person, like if I am newly diagnosed, let’s say, and I have relatively mild symptoms, maybe there’s some MRI evidence, maybe there’s something on my physical exam, but for the most part, I’m living my life and there’s not much disruption. Do I really need to be on a DMT?

Mirla Avila, MD: The answer would be yes, because we know a lot about the natural history of MS. For many centuries we didn’t have MS therapies. You know, the name multiple sclerosis was given in the 1800s, and it was until 1993 when the first drug came out. So we know a lot of what can happen if we don’t treat.

And that is that MS continues to have lesions in our brain and spinal cord, and we don’t have a way to repair the damage that has already occurred. So that’s why it’s so important once you get diagnosed to choose a disease-modifying therapy and to stick with it to prevent damage from occurring.

Susan Payrovi, MD: So I have another question for you. So when we as patients are being recommended to start a DMT, a lot of us actually worry about the side effects, about the impact on the immune system that’s going to help MS but can potentially cause other issues, other side effects. So how do you approach that conversation with patients? How do we think through this problem and weigh our risk versus benefits?

Mirla Avila, MD: That is the reality. We have to choose something that will be okay with us. And, you know, risk and benefits. I think we have to take into account the risk of having MS and not treating, because that also has its share of side effects.

But obviously all the different disease-modifying therapies can offer benefits, but also some certain risks. So it will all depend on if the MS is very aggressive. We definitely want to choose a highly effective medication, because the risk of having a bad outcome with a relapse is going to be much higher than having a side effect with the medication.

If you have a very mild case of MS, then we have many options to choose from. And depending on the mode of administration, either if you’re okay with injections or with pills, we can also have a diverse option for us to choose.

So it is sometimes something nerve-wracking. And I have sometimes patients that tell me, “I’m afraid of side effects.” But to me, something that I want them to understand is that not treating also has its share of side effects that actually can be very, very debilitating, can lead to consequences, to disability. And unfortunately, once a relapse happens, we don’t have a way to revert it.

Susan Payrovi, MD: Okay. So another question I’d love to ask you as a neuroimmunologist is: When is it the right time to switch medications? As a neurologist, how do you think through this problem of this patient is now maybe not responding to this medication and would maybe do better with something different?

Mirla Avila, MD: So there are many reasons. It could be because the patient is not tolerating the medication well. Let’s say they’re not being able to stay compliant because medication is giving a side effect, for example.

It can also be because your immune system outsmarted the drug. So sometimes we do MRIs. As you know, we do frequent MRIs, at least once a year. And that is very important because your MS may have subclinical disease activity. What that means is that you may be feeling okay, but under the surface new lesions can be occurring.

And the only objective way we have to measure that is with an MRI. So once we do an MRI, if we see a new lesion, then that means that that medication is not working for you anymore. And now that we have so many treatment options, it would be advised to switch to something different.

It can also be de-escalating therapy. Sometimes you’re older — maybe you’re 55 or 60 or 70 — you have been stable for many years, and now we’re getting concerned with you being on a disease-modifying therapy that is lowering your immune system.

And there is a de-escalation to different therapies that may have less effect on the immune system. So there are many reasons why we may switch therapies. And I think that’s what I love about treating MS — is that there’s not a straightforward answer for everything.

We don’t have a strict guideline that we go for everything like A, B, C, D, E. We actually have to tailor. So it has a little bit of art in it — that you have to tailor this for each patient, and it can be very different from one patient to the other.

Susan Payrovi, MD: Yeah. I love what you just said — that it’s an art and it really takes experience and good judgment and someone who really uses these medications a lot and understands how to mix and match for the right scenario.

So, you know, there are a lot of patients that have had MS for quite some time. They’ve gone through so many different DMTs and they’ve pretty much failed everything. What do you say to a patient like that?

Mirla Avila, MD: It is a hard spot to be in as a physician also, as well as a patient, because we always want to be able to offer more and more.

But what I can say is the landscape is very promising. There is a lot of research going into something called smoldering neuroinflammation. If you haven’t heard it before, you’re going to hear it more and more, because we have found that not only the immune system that’s causing an acute attack gets activated.

There’s also part of our neuroimmune system — there’s one in particular, a cell that has always been my favorite, even when I was in medical school, called the microglia. And these are immune cells that reside inside our brain, and we’re born with them inside our brain.

Studies have actually shown that these microglia can get activated when there is an attack. But sometimes it doesn’t get deactivated, so it stays, causing a chronic underlying inflammation that we call smoldering neuroinflammation, that can lead to disease activity not related to a relapse.

So what that means is that a patient may not be having a relapse — which we define as a new neurological symptom constant for at least 24 hours, usually associated with a new lesion in the brain — this is not the case.

This is a slow progression, slow worsening despite sometimes your MRIs being fairly stable. But if we look very carefully, we may see that old lesions are getting a little bit larger. Or if we’re able to do another scope of the MRI — another sequence that is called a diffusion-weighted imaging — we’re able to actually see in that sequence that there is microglia activation, and that there are some lesions that are getting larger.

Why is now going to be an exciting field? Because there’s a lot of research. There are some medications that are going to be coming out that are actually addressing this microglia activation. There’s going to be a very new mechanism of action, which we didn’t have before.

Susan Payrovi, MD: Yeah, that’s really exciting to know that we’re uncovering more things that potentially need to be addressed with MS. And do we have any treatments for smoldering MS? Is there anything we can do to address it or slow it down at the least?

Mirla Avila, MD: So we have treatments that are approved for relapsing forms of MS and also for active secondary progressive MS. Most of our disease-modifying therapies are approved for that, but not that have that strong effect in the microglia. But that may change pretty soon because there are in the pipeline a lot of research and hopefully one that would be approved — or several that would be approved — in the near future. So that is going to change, hopefully pretty soon.

Susan Payrovi, MD: Great. And I’d say at the least, we can always keep up our good lifestyle habits to support brain health the best that we can, since we don’t have targeted therapies for smoldering MS.

Mirla Avila, MD: Definitely. That makes a huge difference. In particular, if somebody smokes, we know that that worsens the progression. So that would be a big thing that, as a patient, you can do to improve your quality of life and your brain health.

Susan Payrovi, MD: Yeah, I often tell patients — you know, I’m always talking to patients about nutrition and exercise and sleep — but if there’s one thing you can do to really change the course of your MS, it’s to stop smoking, if that’s something that’s a current habit. So that’s really good advice.

All right, Dr. Mirla, that was really great. Let’s dig into today’s topic. We’re going to be talking about the different treatments for MS. And I would love to pick your brain, as a neurologist specializing in MS, to figure out how you think through all the different classes of these medications and how you differentiate them when you have a patient sitting in front of you and trying to decide what is the best option for this person.

Mirla Avila, MD: I like to present the different options to my patients because I like this to be an informed decision, and also for the patient to have a choice and a say in what therapy they’re going to choose.

The main reason is because I have learned throughout these years of practicing that if the patient has a decision on it, they’re going to be more compliant — rather than just feeling that your doctor told you to take a pill or inject yourself.

So there are many treatment options. And I wanted just to explain a little bit of how interesting the landscape in the MS field has been with the therapies, because we don’t see this a lot in other disorders. And I have been very grateful that all the research has conducted to so many good disease-modifying therapies that we have, that we can now diminish the formation of new lesions by up to even 98% with some therapies — so pretty strong, efficacious therapies.

We have pills, we have injections, we have infusions. They have different mechanisms of action. So we have some that are very interesting because they avoid — or they do not let active cells leave — the lymph nodes. So the cells are functioning, but they cannot go to the periphery and attack your brain and spinal cord.

We have some that are not a drug that does not allow these immune cells to cross through inside the brain and the spinal cord by a membrane called the blood-brain barrier, which is the membrane that separates our peripheral system from our brain and spinal cord.

And we have other medications that will diminish a certain area or a specific target in the immune system — like B-cell therapies, for example. We have B-cell therapies.

So we know that B cells are the ones that can activate T cells and actually can initiate an immune cascade. So by diminishing this, we are also preventing the formation of active T cells.

So, very interesting to me — I love immunology — because there’s just a range of mechanisms of action.

But for a patient, I like explaining more the efficacy and also explaining more on how it’s taken, because I have learned that for a patient, it’s very important to know: Is it going to be a pill? What are the side effects I can experience with them? Is it going to be an injection? Am I going to expect flu-like symptoms or not? And if it’s going to be an infusion, how often will it be?

So I like to categorize: the old injectables — the ones that came out in the market in ’93 — we still have those available. We have several injectables that are called interferons.

We also now have pills, and we have several mechanisms of action of pills — pills that are once a day, pills that are twice a day. And we also have some that you take a set of pills per year, and you only do it that round for two years, hoping that that will be enough and that patients can get into a type of remission.

For that, you have to have been on other disease-modifying therapies before. And then we also have the infusions.

So we have infusions that are given every six months, one that is given monthly. And we also have a CD20 that is given as a one-month infusion. So I sometimes present as categories the CD20, the orals, and then the old injectables.

But I sometimes say, if I know that the patient has a more aggressive MS and I feel that the high-efficacious are going to be the best, I will explain, “I believe that these three or four are going to be best because of this reason.”

And depending on the patient, we’ll go more in detail on each. I have patients that want to know more about the mechanism of action. Others want to know more about, “OK, just how am I going to be able to take this, and is it going to interfere or not with my quality of life?”

And some, for example, live far away and it’s hard to go to an infusion center, so they prefer to have something that they can dose themselves — like a monthly injection, for example. So it varies a lot from one patient to the other.

Susan Payrovi, MD: That was a really nice overview of the DMTs. And while not the focus of today’s session, maybe we could just briefly touch on medications for relapse management and symptom management.

Mirla Avila, MD: So those are different.

Relapses — we still use steroids. Sometimes if the steroids don’t work, or if patients cannot tolerate it, we may do plasma exchange or IVIG. But usually steroids are the way to go, and we give one gram for three to five days depending on how aggressive the relapse is.

So it’s now important to know that steroids also have their share of side effects. It’s something to be used only when there’s an acute attack, because they really don’t prevent damage in the future. So it’s important for us to treat that and to choose a disease-modifying therapy to prevent further damage.

Susan Payrovi, MD: Great. And then as far as symptom management — you know, for gait or fatigue or bladder issues — there are medications, there are also lifestyle habits that can help. But those will be the topics discussed in other episodes.

So, you know, I always — actually, I’m so grateful that in my lifetime the number of DMTs has exploded. Now there are oral therapies available. Could you just give us a little background on the history of DMTs?

Mirla Avila, MD: So yeah, and I would like to give a little background on the history of MS to understand also the DMTs. And I’ll try to be quick with this, because I’m fascinated about the history of medicine.

But I don’t know if you know that the first case of MS was actually described in literature — it was a Catholic nun called Lidwina, who was an avid skater. She started when she was 15. She started tripping and having difficulty skating, and the literature describes somebody that had relapsing-remitting MS and eventually secondary progressive MS.

They describe optic neuritis getting better and then her having difficulty walking. And long story short, it was until the 1800s — this was the 1400s — and it was until the 1800s when the name multiple sclerosis was given by Dr. Charcot, who was the father of medicine.

But it was until ’93 when the first DMT came out. So for all those centuries, we didn’t have treatment options, and we knew what could happen if we didn’t treat MS.

And then, when I was doing my fellowship, we had just the injectables and one infusion. And then I remember when the first oral came out — we had a long list of patients that we needed to get into the new drug. Everybody wanted to try the new pill.

And it just has been fascinating to be practicing neurology and MS in this landscape, that now we have gone to multiple oral medications and now infusion medications and very strong, efficacious, self-administered medications.

I don’t doubt that we’ll have a cure one day, or we’ll have a way to repair myelin. And hopefully I’ll still be practicing and be able to offer this to patients, because that’s going to be super exciting. But just in these past 20 years, the landscape has changed dramatically — more than in many other areas of medicine.

Susan Payrovi, MD: Yeah, I do remember a neurologist telling me back when I was first diagnosed something like, “If you’re going to have MS, this is the best time to have it.” And I was like, I’m not sure I’m excited about that or how I feel about that comment, but I understand that this is a very different era than what people experienced prior to the ’90s.

And I just feel that it’s so important for people to have actually established care with a neuroimmunologist. Maybe that person is too far for you to see all the time, but there is an art to navigating these medications and making sure that you’re really on the right therapy at the current time.

So, Dr. Mirla, as an integrative physician, I have a lot of patients that are often confiding in me that they have a lot of fear around starting a DMT. They’re afraid of side effects and what it might do to their immune system.

How do you help patients navigate this conversation so that they feel comfortable with their therapy and that they will actually take it and will have better compliance — and hopefully better outcomes?

Mirla Avila, MD: I really think that education is key. I love talking, I love educating — but I do this also in my visits with each patient. I think if they understand, if you as a patient understand, the relevance of being in a therapy and the reason why we want to prevent damage — because we don’t have a way to repair once that happens.

The other very important thing that I want my patients to know is that the medication that you’re on to prevent relapses, or your disease-modifying therapy, is likely not going to make you feel better. You’re not going to have less fatigue, less pain, less spasticity, less bladder issues.

So I want them to know that it does not mean that the medication is failing them. If we are stable in regard to MRI and we’re not having any more relapses, then that medication is really working for them.

And we can definitely treat the symptoms — I don’t want to minimize. Symptoms can be very bothersome and can interfere with your quality of life. But I want them to know that the disease-modifying therapy has a different purpose than the symptomatic therapy.

The other thing is that we have to tailor this disease-modifying therapy for your own MS, and this is based on your age, your stage of MS, your gender — as we were talking — your ethnicity also.

So understanding these things, I think knowledge is power. And I think it makes a difference. And you can take also more ownership and control of your multiple sclerosis.

I would also add that if you are experiencing any concerns or questions, call your physician. Ask them those questions. Don’t stop medications cold turkey, because sometimes some medications can lead to rebound effect. And as I said again — and I cannot stress enough — once we have a relapse or damage, we don’t have a way to revert it.

I like to explain to my patients a little bit like when we get diagnosed with another chronic disease — high blood pressure, diabetes. I have coronary artery disease and hypertension.

I know that if I don’t take my blood pressure medication, I may not feel any different, but I may be developing consequences from not taking it that later on I’m going to pay the price with a stroke or something like that.

So I explain to patients that it is like dealing with another chronic disease. We have to be on something to prevent damage. But the good thing is that we have a lot of good treatment options to choose from. And if one is not working, another one may work better.

Susan Payrovi, MD: Thanks for watching. Don’t forget to check the show notes for our bonus segment featuring burning questions from our viewers. Also, look for our next episode coming soon — “The Gut Microbiome and Why It Matters So Much for MS.”

Mirla Avila, MD: Thank you, everybody.