Future Thoughts on BTK Inhibitors in Multiple Sclerosis


Ahmed Obeidat, MD, PhD; Benjamin Greenberg, MD; and Hesham Abboud, MD, discuss their future hopes and concerns for the use of BTK inhibitors in the treatment of multiple sclerosis.

Ahmed Obeidat, MD, PhD: We talked about BTK inhibitors in detail, to the extent of what we know. There are many things that's still unknown about this class of medications. I want to ask both of you before we go to the next a small topic, is to have final thoughts about BTKi. And Dr Abboud, we ask you a lot about the excitement about it, but also what your concerns and final words about BTKi before we talk about some other trials.

Hesham Abboud, MD: Safety is always a concern with any new class of medication, especially in immunotherapeutics. One big concern of this class is the fact that they have a multi-target approach. They act in different cells, and they impact different pathways in the immune reaction. The big question is, concerning safety signals with the phase 3 trials, are we going to see concerning safety signals in real-life use over time? This is a big one. I always have a personal concern about fixing one thing and then breaking something else when it comes to immunotherapeutics. And there has been some early case reports showing some paradoxical worsening of desalination with TKIs, very few case reports. But I'm curious about this and I'm keeping an eye on this and they know that at least one of the phase 2 trials, one of the reported adverse effects was severe MS relapse. That's something we'll find out as we keep an eye on those phase 3 clinical trials. But yes, atrogenic inflammation is something that always worries me.

Ahmed Obeidat, MD, PhD: It is. Yes. That's great points. And Dr Greenberg, any final words of BTK inhibitors?

Benjamin Greenberg, MD: Yes. I love your final words really from the trial data perspective and understanding safety and efficacy. If I had to give final words about BTKi, that's concerns about using the drugs in patients. And I agree 100%. I have concerns about the practitioners when it comes to BTK inhibitors and that this is going to be whenever we get a new class of agents within any sub-specialty within medicine, there's a learning curve. And this is going to be a steep learning curve, for us as MS clinicians. This is a very different molecule than we're used to using. It's a very different target than we're used to treating in MS. And there's a lot of work we need to do as clinicians before these 3, 4, 5, 6, probably up to 8 different clinical trials or more finish over the next 4 years. We are going to be inundated with data. And it's incumbent upon us as professionals to get educated on the nuance differences between these so that we can best advise our patients on what we know, what we don't know. And my excitement is definitely there around the new class of medication. And I would love to see a single agent treat both relapsing and progressive. That'd be one of the multiple holy grails we could get to in multiple sclerosis therapeutics and change the way we practice and change the way our patients do. It's not going to be easy and there's going to be a lot of noise. And I just want us as a field to make sure we're ready to receive that information, process that information, and then utilize it in a scientifically rigorous, but human way to treat our patients.

Ahmed Obeidat, MD, PhD: Yes, this is great. It’s helpful advice, I would say to us and our audience here because it's a new class and we have lots of unknowns and maybe even once the trials are done, we're still going to have some things to follow up on with open-label maybe, and some more other real word studies on this.

Transcript Edited for Clarity

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