Experts recommend approaches for special cases including ocular myasthenia gravis, pregnant patients and children with myasthenia gravis, and more.
Dr. James F. Howard: Let’s change topics again. But on the course of treatment, the topic of treatment, do you have differences in some types of myasthenia, for instance. We spoke a little bit about ocular myasthenia in your use of pyridostigmine alone sometimes. But if that's not doing the job, do you treat them any differently than someone with a generalized disease?
Dr. Nicholas J. Silvestri: I don't think so. Well, it depends on the patient and it depends on the situation. When I talk about individualized approach to therapy with the residents, I say, if it's an older patient with mild non-disabling ptosis and it prevents them from reading late at night, but they can get away with it, that's probably OK. And that's a generalization. But if it's an airline pilot who has intermittent diplopia or ptosis that causes him or her to be functionally blind, that's a big problem. We have to get more aggressive about that. And those patients that are ocular that are really debilitated by it, if cholinesterase inhibitors in and of themselves don't do it, I will move on to steroids. And in those patients that I can't get on a low enough dose of steroid that I feel comfortable that the risks and benefits are somewhat maximized, at least that ratio is maximized, I will move on to an early immunosuppressant. I've got a couple of people that had quite severe ocular myasthenia who are maintained, for example, long-term, doing really well on mycophenolate.
Dr. James F. Howard: And I think one of the problems that we're starting to recognize, and it needs to be confirmed is that the longer one has ocular symptoms. The less potential for improvement over time. And there's now some studies looking at MR Imaging of the volume, the diameter of ocular motility muscles, and with atrophy. And then can you recover that? And so, that was an interesting presentation that was done recently. And I think it may change some of the lack of aggressiveness that we have, and to become even more aggressive to try and get these under control. We know there's a subgroup in South Africa, for instance, Caucasians in whom they become refractory to therapy and then never recover. And Janine Heckman feels that one must be very aggressive very early. And if one is to keep them out of ocular dysmotility for life.
Dr. Nicholas J. Silvestri: Yeah. On point, I have two patients, relatively young African Americans who didn't come to me a little bit later on in their disease course, who basically have ophthalmoplegia. And I don't quite - we're not able to drill down into their exact dissent in terms of where in Africa. But I do think I've seen a similar phenotype in some patients that were really undertreated at onset.
Dr. James F. Howard: How about MuSK MG?
Dr. Nicholas J. Silvestri: I'm a big fan of rituximab in MuSK MG. I think the literature is pretty unequivocal in terms of the effects of B-cell depleting therapy and the beneficial effects in myasthenia. I often won't use pyridostigmine when I have that diagnosis for the reasons you mentioned before; it causes worsening and more patients than it helps. And I will initially stabilize a patient out on steroids. In the past, I had tried oral immunosuppressants at first. But I just wasn't getting a lot of bang from my buck, so to speak with medications like mycophenolate. People would have residual symptoms often disabling. As you know, it tends to be a little bit more of a severe phenotype. Honestly, the last few patients I've diagnosed with MuSK, I've gone fairly early to rituximab and often it takes just one cycle to give them a pretty long-lasting response. It does seem like an aggressive approach, but I think that it's been quite successful in my experience.
Dr. James F. Howard: Yeah, rituximab is my go-to drug, and I now use it first-line because of the improvement in the relative lack thereof using other ISTs. And we'll treat them with two cycles and then we sit back and wait. Time zero, then again, it's six months. And have found that very effective in the overwhelming majority of patients. Do you do anything different with LRP-4? I know it's exceptionally rare. Recently identified, but do you treat them any differently than any of our other subtypes?
Dr. Nicholas J. Silvestri: I would say not really. I've only got a small number of LRP-4 positive patients, and they tend to have a little bit more of a mild phenotype. I would say I treat them fairly similarly to acetylcholine receptor-positive patients. But I've not had to escalate their therapy thankfully to some of the later lines of therapy.
Dr. James F. Howard: How about children?
Dr. Nicholas J. Silvestri: Yeah. Children, we talked a little bit more about thymectomy. It's something I've employed in a number of children I've treated over the years. And I do worry about using relatively high doses of steroids in children for a couple of reasons. Number one is growth and number two is behavior issues. I also treat patients with Duchenne dystrophy and I see a lot of problems with steroids and behavior in those patients, but also in the patients, I've seen with MG. In terms of long-term immunosuppressants, again, I do worry about that, especially as children, female children become women of childbearing age. I do worry about those medications in women of childbearing age that have potential teratogenic properties. Something to keep in mind. I would say I employ thymectomy in those children fairly frequently. And I do try to minimize the doses of other medications just to try to mitigate side effects.
Dr. James F. Howard: Yeah. And I would agree completely. Thymectomy early; medium doses of steroids rather than the very high doses. And I'll often use, IVIG because they can go into the home to administer it. I think that's going to change and will come to that in a bit in the next section. But I think there's a role for our newer therapies in these kids. And we're having success. The other big one that people ask about is pregnancy. And do you manage them any differently?
Dr. Nicholas J. Silvestri: Yes. As I hinted at a minute ago, there are some medications that we try to avoid in pregnancy, specifically suppressants. Generally speaking, I think of pyridostigmine, prednisone, IVIG all is OK in pregnancy, relatively speaking. And I think over time, as I'm sure we'll get into, again, some of the more emerging agents though, we don't have a lot of data on human pregnancy yet maybe options for those patients as well. But certainly, when you're treating the pregnant woman, you have two patients and you've got to be mindful of both.
Dr. James F. Howard: And it's our firm belief that anyone who is pregnant with MG needs to be followed in a high-risk pregnancy clinic. And you as a team taking care of the two patients that Nicho has spoken about we taper them off their ISTs. Some feel that Azathioprine is safe. I disagree with that. There's very old literature that it's second generation that has turned a genetic effect, not first-generation, and that scares me to death. And so, we'll pull them off. We will use prednisone. Prednisone does not cross the placental barrier. But it's the adverse events to the prednisone in mom that then subsequently affect the fetus; hypertension, diabetes, et cetera, but prednisone doesn't cross. From that perspective, it's fairly safe. And then with the neonates, we treat as if they were whatever that subtype is as a child other than thymectomy, I won't do it on neonates. But I've often done plasma exchange. Not using a big system, but rather small volume removals and spun down and reinfusion, and that's been effective as well.
Transcript Edited for Clarity