Recommendations from neurologists James F. Howard Jr., MD and Nicholas J. Silvestri MD, FAAN for addressing acute exacerbation in patients with myasthenia gravis.
Dr. James F. Howard: What about crisis, acute exacerbation? What is your approach in managing these?
Dr. Nicholas J. Silvestri: I think if it's a true full-on crisis, so if it's respiratory involvement, those patients are coming to the hospital and we're using plasmapheresis. I know some people like to use IVIG in crisis. In my experience, it just doesn't work fast enough. And I try to - obviously, if we can prevent people from being intubated or if they are intubated to get them extubated as soon as possible to prevent some of the side effects or the problems that can occur while people are intubated. Plasma exchange. If a patient is more slowly getting worse and it doesn't really involve the respiratory system, then I might do IVIG, but for a full-on crisis, it's plasma exchange. How about yourself?
Dr. James F. Howard: I rely very much so on plasma exchange. Grew up with it from the 70s and have stuck with it. I find it more predictable and longer-lasting than IVIG. And so, we've relied on it. Now, we have a phenomenal blood bank service who does our procedures and in placing lines. And more than half of our lines are peripheral lines. We don't need catheters.
Dr. Nicholas J. Silvestri: That's great.
Dr. James F. Howard: Or subclavian, jugular, et cetera. And it's just a superb team to work with. And so, that's a benefit that many folks don't have, and I can see where they gravitate to IVIG. But to me, it's the way to go. There's a term that has popped up over the last several years and regrettably, I'm part of the reason and that's refractory myasthenia gravis. And it's probably a misnomer as far as I'm concerned because virtually every patient will have some response to therapy. Technically, they're not refractory. But refractory has been brought up. How do you interpret it? What is a refractory patient to you?
Dr. Nicholas J. Silvestri: Yeah, I think that you are right. I think the nomenclature is a little unclear here and probably there is a better term for it. Because when I think of a refractory patient, first of all, I'm thinking about a treatment-refractory patient. And then the question is, how many lines of therapy then qualifies a patient as treatment-refractory? And I think if I rely on the literature, which I think to an extent bear out in clinical practice, it's that patient that has probably failed two or sometimes three steroids, and maybe two IST steroids and IST and IVIG or it's not so much they failed it, whereas we didn't get the optimal efficacy or there were side effects that were intolerable. And I think either of those would qualify. That's one way to look at it. The other way to look at it are patients that have very severe disease. Now, that may not be the same exact population, but I think it's a big overlap generally speaking. Those are the two operational definitions of it I use. And why I think it's helpful in some regard is, I do think that using that terminology or thinking about these cases in that particular way allows us to escalate therapy and allows us to escalate therapy often quickly so we can get better disease control.
Dr. James F. Howard: One of the difficulties though is that many people have used clinical response in the definition. And we've all started to think about the treatment burden, the adverse event profiles that our drugs produce. And to me, that qualifies somebody as a non-responder, non-adequately responder and warrants change in therapy. The problem we get into is that the time from drug initiation to some semblance of effect is months. As we start cycling through our therapeutic toolbox, we start losing time for these patients; years in some instances. And with that comes a huge social-economic impact of lost job, lost wages that is regrettable and unfortunate. And I think as we'll talk in a bit, the advent of our newer therapeutic tools, which are much more rapid in onset of action that we may be able to get around this.
Dr. Nicholas J. Silvestri: Well, I think that's true. I think the waiting game, waiting a year, waiting a year and a half, I think those days may be coming to a close very soon with the advent of some of these therapies.
Dr. James F. Howard: Do you monitor your patients longitudinally with anything special, other than your clinical history and exam?
Dr. Nicholas J. Silvestri: Yeah, we use the MG-ADL in clinic. Patient-reported outcome measure as you well know that really, I think, accurately portrays for the most part how someone's activities to daily living or functioning is impacted by their MG. I monitor that in most of my patients. Now, truthfully, I don't monitor in patients who are asymptomatic because as much as I want to see an MG-ADL of zero over and over again, it doesn't really serve much of a purpose. But for most of my new patients, certainly, the patients that are more severe, the patients where I am changing therapies, I do monitor the ADL to try to get a sense of their treatment response.
Dr. James F. Howard: Yeah. And for the audience, it's a very simple measure to perform under two minutes. Literature will say 10 minutes, but it's much quicker than that. And trend analysis is very helpful. And as you see the ADL score increasing, you know that you're losing control of the patient. And one should think about what alternative therapies one might consider. And similarly, as it's improving, it's giving you the reassurance that your patient is responding, stay the course, do what you're doing, and shoot for that outcome of minimal manifestations, minimal symptom expression.
Transcript Edited for Clarity