Disease modifying therapy (DMT) in multiple sclerosis (MS)

Ahmed Zayed Obeidat, MD, PhD: hello and thank you for joining Neurology Live® companions and prospects Presentation entitled “Optimizing treatment of relapsing-remitting multiple sclerosis with oral therapy.” I am Dr. Ahmed Obeidat, Associate Professor at the Medical College of Wisconsin in Milwaukee. Today is Dr. Mark Friedman. He is Professor of Medicine in the Department of Neurology at the University of Ottawa, Director of Multiple Sclerosis Research at the Ottawa Hospital Comprehensive Campus, and Senior Scientist at the Ottawa Hospital Research Institute in Ottawa, Canada.

Today we will discuss the use of oral therapy in the treatment of relapsing-remitting multiple sclerosis. [MS]A rationale for treatment selection based on long-term and real-world data and how recent and emerging treatment advances may transform care for patients with relapsing-remitting multiple sclerosis. I will explain what Thank you for your participation. Let’s get started. Welcome, Dr. Friedman.

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: thank you.

Ahmed Zayed Obeidat, MD, PhD: Thank you for joining us today. Let’s start by talking about disease-modifying therapy classes. The past two decades have seen a number of disease-modifying therapies hit the market. we are lucky Our patients are lucky. Because now you have a choice. I would like to touch on the different classes and the rationale for their development for the treatment of relapsing-remitting multiple sclerosis.

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: It’s actually been probably 30 years since the first disease-modifying drug was tried in multiple sclerosis. I think many of these have evolved as our understanding of the underlying disease has improved. It has become a prototypical autoimmune disease for the development of cancer. Compared to rheumatoid arthritis and other conditions that involve multiple systems, it’s obvious. In MS, it’s the central nervous system and that’s it. We’ve been lucky, but we’ve put in quite a bit of effort through clinical trials. This has resulted in a lot of interest from the industry in developing new treatments.

The class of medicines we had grew out of a basic understanding of what immunology is. We start with what we call immunomodulators. Before the advent of immunomodulators, we poisoned everyone with chemotherapy that not only destroyed the immune system, but also knocked out the hematopoietic system and had many negative effects on different organs. Long-term treatment of any kind did not help. It was kind of a last minute fuss and the patient was too late. So the development of immunomodulators gave rise to the idea of ​​controlling the immune system to keep disease at bay and not put patients at risk. So while the entire first class of immunomodulators, and the ones we continue to use immunomodulators for today, can somehow stop the disease, they are not immunosuppressive. This ensures that you have a long-term safety record that is second to none.

Unfortunately, for many patients, that adjustment alone is not enough. They have more disease activity and they need something more powerful. We knew that immune cells were somehow generated outside the brain, so there was a whole group of drugs that were very effective, but they had to get inside the brain to cause disease. So is there a better way to control the disease than to stop it from entering the brain?

Ahmed Zayed Obeidat, MD, PhD: That is correct.

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: We had treatments like natalizumab, which blocks these cells from moving to the brain.We had S1P [sphingosine-1-phosphate] There are five receptor agonists that we are currently using. They all work the same. They modulate receptors on the surface of lymphocytes through their normal migration in and out of lymph nodes. It’s like if you walk into a parking lot and get a ticket, you need a ticket to get in and out of the lymph nodes, but the medicine takes the ticket away.

Ahmed Zayed Obeidat, MD, PhD: That is correct. they can’t get out

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: they can’t get out I call this the “Hotel California” effect. you know why?

Ahmed Zayed Obeidat, MD, PhD: Interesting, please tell me why.

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: You can check in, but you can’t leave once you’ve listened to the song. That’s what S1P receptor agonists do. If you don’t control the disease, you’re stopping these peripherally generated immune cells from entering the central nervous system, if you think about it. They are still there and if you stop these drugs….

Ahmed Zayed Obeidat, MD, PhD: they are chasing…

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: They’re trying to get into your brain. His two classes of drugs, blood-brain barrier blockers and lymph node blockers, have been associated with rebound problems. So you have to configure for that. When transitioning, I think we’ll talk about sequencing later, but when transitioning from any of these treatments, you need to keep this rebound in mind and mitigate it.

Ahmed Zayed Obeidat, MD, PhD: That’s very important because you don’t want any harm done there.

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: that’s right. These anti-trafficking drugs also interfere with normal immune surveillance. Think of it as your immune system going in and out of your organs looking for viruses, malignant transformations, etc. That’s how the immune system works. Think of it like a night watchman walking through a large office tower. He has all the office keys. He was walking down the hallway, went in, checked out of the office, all was well, closed the door. What do these anti-trafficking drugs do? They take away the keys. As such, the night watchman can only roam the corridors. He doesn’t know what’s going on in the individual offices. So problems like PML arise. [progressive multifocal leukoencephalopathy]Normally, if the immune system is alert, and there are guards there, PML will not occur.

Ahmed Zayed Obeidat, MD, PhD: it won’t happen.

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: We don’t get PML, we don’t get other opportunistic infections, we probably don’t get the malignancies we’ve seen before. So I think there is a limited amount of time that these drugs can be used. One of the problems that arise is, unfortunately, getting older. As we age, our immune system naturally becomes compromised and many problems begin to arise. Long-term use of drugs such as S1P makes me nervous.

Ahmed Zayed Obeidat, MD, PhD: What about immunosenescence associated with the disease itself? Is it helpful or maybe not?

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: No, I wanted to talk about that later, but you made an important point, so let’s get to it here. At what point can disease-modifying therapy be safely discontinued? Does the disease need to be treated permanently?

Ahmed Zayed Obeidat, MD, PhD: don’t understand.

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: There is a sense that disease activity naturally fades away with aging and aging of the immune system. This is because as patients get older, they have fewer recurrences and less MRI activity. We remain vigilant against this development, which we do not yet fully understand.

Ahmed Zayed Obeidat, MD, PhD: that’s right.

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: All of the treatments we offer are to slow or stop the progression of this disease, to keep people from becoming disabled, and that’s what they’re all about. As you get older, you may not need it. Alternatively, we may be able to reduce escalation from more suppressive treatments to treatments that are safer in the long term.

Ahmed Zayed Obeidat, MD, PhD: Is it a modulator?

Mark S. Friedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC: That information is not available today. We have not done adequate research to know when it is safe to sedate or when the drug can be discontinued with confidence that these patients will not relapse.

Edited transcript for clarity