Dr. Edmundson: 
This is CE on ReachMD, and I'm Christyn Edmundson. I'm here today with Dr. Gil Wolfe.

So far, we've talked about why setting clear treatment targets in gMG matters and what those targets are. Now, we're diving into what one of those targets really means, minimal symptom expression or MSE, and how it's reshaping how we define treatment success.

So, minimal symptom expression is having an MG-ADL score of 0 or 1. Let's start there. So, Dr. Wolfe, when you're looking at that MG-ADL score of 0 or 1, what does that really tell you about where a patient stands and how they're doing?

Dr. Wolfe: 
Well, it generally and pretty much universally tells you that the patient is doing really, really well. I even would argue if you have an MG-ADL score of 0 or 1, not only is your disease control quite good, but you're probably not having significant side effects from therapy either, because you probably would be hitting some of those items if you were having some tolerance issues with medications.

I have never seen a patient with an MG-ADL of 0 to 1 who is not doing really well. So, it's an aspirational treatment goal. It really represents near complete or fully complete control of symptoms with really no or minimal functional impact on activities of daily living. It's been used in clinical trials as a secondary outcome.

We know that patients achieving MSE, minimal symptom expression, maintain a stable disease state, with nearly 87% of those reaching this status remaining in remission or minimal manifestation at 12 months.

The other thing about it is it focuses on patient-centered goals. Again, it's a derivative of the MG-ADL, which has served as the primary outcome in some fashion for all of the trials that have led to targeted therapy approvals by the FDA since 2017.

A quick question for you. How do you see MSE compared to minimal manifestation status, and how should clinicians use these endpoints differently when it comes to treatment decisions like tapering a medication or escalating a therapy?

Dr. Edmundson: 
Yeah, that's a great question. So, let me start by saying both minimal manifestation status and MSE are highly desirable treatment outcomes. And I would be happy with a patient achieving either. Like, if I can get someone to MSE or minimal manifestation status, that's great. We're where we want to be. And similarly, if they're not at minimal manifestation status or minimal symptom expression, MSE, I may try to escalate their therapy to work to get them to that better-controlled state.

Essentially, minimal manifestation status is a patient who has no symptoms from myasthenia gravis on a day-to-day basis but has some physical findings of myasthenia gravis on exam. In contrast, a patient with minimal symptom expression just by definition has an MG-ADL score of 0 or 1. Such patients may also have exam findings of myasthenia.

A key distinction here is that not every symptom of myasthenia gravis is captured in the MG-ADL score. The big gap that is sometimes missed is neck weakness, right? Neck flexion or extension weakness is not captured in the MG-ADL score. So, in theory, a patient who has some neck flexion weakness from time to time, they're going to have an MG-ADL score of 0. Similarly, a patient who has no symptoms other than mild occasional double vision is going to have an MG-ADL score of 1.

So, I see MMS as being a little bit stricter in terms of its definition, but in either case, a patient who is at either minimal manifestation status or MSE is very well controlled. And it's usually when patients are at one of these statuses that I would begin to taper immunosuppression, whether that's steroids or whether it's other sort of immunotherapies.

When a patient gets to one of these points is when I'll say, okay, what can we start taking off to keep them ideally at a really well-controlled point, but on as little therapy as they need, right?

So, this has been a great micro discussion. Our time is up and thanks so much for listening.