Myasthenia Gravis Management: Unmet Needs & Future Course

Podcast Transcript

Neuro Pathways Podcast Series

Release Date: July 1, 2024

Expiration Date: July 1, 2025

Estimated Time of Completion: 32 minutes

Myasthenia Gravis Management: Unmet Needs & Future Course

Yuebing Li, MD, PhD

Description

Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.

Learning Objectives

• Review up to date and clinically pertinent topics related to neurological disease
• Discuss advances in the field of neurological diseases
• Describe options for the treatment and care of various neurological disease

Target Audience

Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.

ACCREDITATION

In support of improving patient care, Cleveland Clinic Center for Continuing Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

CREDIT DESIGNATION

• American Medical Association (AMA)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
  
  Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

• American Nurses Credentialing Center (ANCC)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

• Certificate of Participation
  A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

• American Board of Surgery (ABS)
  Successful completion of this CME activity enables the learner to earn credit toward the CME requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

Credit will be reported within 30 days of claiming credit.

Podcast Series Director

Imad Najm, MD
Epilepsy Center

Additional Planner/Reviewer

Cindy Willis, DNP

Faculty

Yuebing Li, MD, PhD
Neuromuscular Center

Host

Glen Stevens, DO, PhD
Cleveland Clinic Brain Tumor and Neuro-Oncology Center

Agenda

Myasthenia Gravis Management: Unmet Needs & Future Course

Yuebing Li, MD, PhD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

Yuebing Li, MD	Alexion Other activities from which remuneration is received or expected: Member of Clinical Practice Scientific Advisory Board Research: Principal investigator Immunovant Consulting Research: Serve as principal investigator in an ongoing trial. ArgenX Consulting Research: Principal investigator. Also receieved grant support from Argenx.
Imad Najm, MD	Eisai Advisor or review panel participant NIH Other activities from which remuneration is received or expected: Research Funding LivaNova, PLC Advisor or review panel participant SK Life Science Inc Advisor or review panel participant Teaching and Speaking
Glen Stevens, DO, PhD	DynaMed Consulting

The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Cindy Willis, DNP.

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC Contact Hours, OR CERTIFICATE OF PARTICIPATION:

Go to: Neuro Pathways Podcast July 1, 2024 to log into myCME and begin the activity evaluation and print your certificate If you need assistance, contact the CME office at myCME@ccf.org

Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.

Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neurorehab, and psychiatry.

Glen Stevens, DO, PhD: Myasthenia gravis is a disorder that can vary in onset, pattern, progression and severity, as well as underlying cause. However, only medications for antibody-positive generalized myasthenia gravis are FDA approved, leaving some to wonder what's best for individuals who fall outside of this diagnosis. In today's episode of Neuro Pathways, we're discussing the unmet needs of individuals with myasthenia gravis, particularly those with atypical myasthenia gravis, and the future directions of care. I'm your host, Glen Stevens, neurologist, neuro-oncologist in Cleveland Clinic's Neurological Institute. I'm very pleased to have Dr. Yuebing Li join me for today's conversation. Dr. Li is the head of the Myasthenia Gravis Program in Cleveland Clinic's Neuromuscular Center and Neurological Institute. Yuebing, welcome to Neuro Pathways.

Yuebing Li, MD, PhD: Thank you, Glen. Thanks for having me.

Glen Stevens, DO, PhD: So Yuebing, let's let the audience know who you are a little bit. Tell us how you made your way to Cleveland, what you do on a daily basis for patients in the Neuromuscular Department?

Yuebing Li, MD, PhD: I came from China to the United States in 1991. I stayed in school to earn a PhD degree, then started to do neurology residency and fellowship. I did my training at University of Cincinnati. After that, I went to Allentown. And in 2012, I joined Cleveland Clinic. Since then, I've been focusing on neuromuscular disorders, particularly myasthenia gravis. So I see a lot of patients with myasthenia gravis on a daily basis. And I also do EMGs making diagnosis. And in some spare time, I do research and educate people.

Glen Stevens, DO, PhD: All right, I hope you have some fun in there too outside of work.

Yuebing Li, MD, PhD: Absolutely.

Glen Stevens, DO, PhD: So we're going to concentrate mostly on what we're going to call, I guess atypical myasthenia gravis versus generalized typical antibody-positive myasthenia gravis. But I think we have to talk about general myasthenia gravis to begin with. So my understanding is that it's an autoimmune disease against the neuromuscular junction where you develop an antibody that affects the postsynaptic membrane receptors. So that when you have an electric impulse that stimulates the nerve, you just don't get the response you should get because there's nothing at the other side of it to capture it, to have the response and cause the muscle contraction. So am I right about that? Is it changed? Is it different than that?

Yuebing Li, MD, PhD: No, you are absolutely right. There is this acquired autoimmune myasthenia gravis, which is classically autoimmune. And in the majority of these patients there are antibodies, and there is less than 5-10% in people, the antibodies cannot be detected. But the belief is that either it's antibodies we have not been able to identify, or the antibody at a low concentration that it cannot be detected. There is a congenital myasthenic syndrome, which it's not autoimmune, it's genetic. And when we talk about myasthenia gravis, we mostly talk about autoimmune-acquired myasthenia gravis.

Glen Stevens, DO, PhD: So let's talk about the antibodies with the typical myasthenia gravis. First, go through some of the antibodies for us. So somebody comes to see me, I think they have it. I find a panel somewhere of antibodies, what are the antibodies I'm sending away?

Yuebing Li, MD, PhD: There are mainly three antibodies now we can evaluate and measure. The most common is antibody against acetylcholine receptor. The acetylcholine, it's the molecule that is released from the nerve, then reach the muscle. Approximately 85-90% of patients with myasthenia gravis, I'm talking about the general myasthenia gravis, have this antibody. The second most common antibody is called the MuSK, M-U-S-K. That is mainly seen in patients with a general myasthenia gravis, and approximately 5-6% of the patient with general myasthenia gravis have MuSK antibody. The third one is LRP4 antibody. The frequency has been reported with different numbers. Our belief based on our clinical experience, is approximately 1-2% of the patients with myasthenia gravis may have an LRP4 antibody, or even less than that.

Glen Stevens, DO, PhD: Mm-hmm. Do you typically measure it in patients, or you do the standard antibodies, and if they're negative, that you'll check it? Is there a specific phenotype?

Yuebing Li, MD, PhD: So it really depends how urgent the situation is. In myasthenia gravis, some people can present with very, very significant symptoms, and you know that you needed to make a diagnosis right away. So sometimes you check two or three antibodies at the same time. Then there are people who present insidiously. And you can check one antibody, and if it comes back, you can do another antibody. You are right, different antibodies give you different phenotypes. The most common antibody is acetylcholine receptor antibody. Most patients started with eye symptoms, double vision, droopy eyelids. A small portion presented with speech or swallow issues. MuSk antibody-positive myasthenia gravis on the other hand, typically presented less eye symptoms, and they typically presented with more speech, swallow, or neck weakness. People with LRP4 antibody, typically they present with mostly predominantly eye symptoms or mild myasthenia gravis.

Glen Stevens, DO, PhD: So if you look at the acetylcholine receptor antibodies, the binding, modulating, and blocking, do you need to check all three of them?

Yuebing Li, MD, PhD: Probably not. The person who invented this antibody, the blocking and modulating antibody was Dr. Daniel Drachman at Johns Hopkins. He actually said one time, "I was the person who invented these antibodies, I don't use them at all." The most specific and sensitive antibody is the binding antibody. If the binding antibody is negative, you can check blocking and modulating antibody. I would say, probably additional 2% of patient may have positive modulating antibody with negative binding antibody. We have run into very rarely, one or two cases of a patient with a positive blocking antibody, and never had the other antibodies. But I would say the blocking antibody is probably the least useful among three.

Glen Stevens, DO, PhD: Okay. And what about striatal muscle antibodies? Is that one of the antibodies that's sort of a marker for thymomas, or that's not part of the typical antibody panel that you look at?

Yuebing Li, MD, PhD: So there has been some conceptual evolution on that. If you look at patients who are positive for striational antibody, typically they are elderly MG patient who does not have a thymoma. But if you see a younger patient, younger, we talk about age less than 40 years of age. If they have positive striational antibody, it's more likely to be thymoma-related myasthenia gravis. So in a younger population, there may be some indication, some value for the striational antibody to be positive. But in the elderly, when you are a striational antibody-positive, it does not mean you have a thymoma.

Glen Stevens, DO, PhD: So you've alluded to this a little bit, and correct me if I'm wrong, but I think you said the MuSK antibody-positive people present more bulbar symptoms.

Yuebing Li, MD, PhD: That's correct.

Glen Stevens, DO, PhD: Okay. What about the thymoma patients? Do they have a specific presentation, or they can just have a generalized myasthenic presentation?

Yuebing Li, MD, PhD: A very, very interesting question. So every patient with myasthenia gravis, whichever phenotype. When you are diagnosed with myasthenia gravis, typically you will need a CT scan of the chest, or MRI of the chest looking for thymoma. But most myasthenia gravis who have a thymoma is positive for acetylcholine receptor antibody. There are less than 5-10 cases that has ever been reported who have a thymoma and are positive for MuSK antibody. So when you have myasthenia gravis and you are MuSK antibody-positive, then theoretically you do not need a CT scan of the chest.

On the other hand, most a patient who has MG, myasthenia gravis, and who also have thymoma, typically their myasthenia gravis is generalized rather than ocular. Very few cases, small cases of ocular myasthenia gravis has been found to be associated with thymoma. So typically when you have a thymoma, you have MG, it's a generalized myasthenia gravis, who are positive for acetylcholine receptor antibody.

Glen Stevens, DO, PhD: Should all these patients have an EMG?

Yuebing Li, MD, PhD: No, we have gone away from that. Typically, there are maybe three clinical scenarios you might need an EMG. Special for EMG called the repetitive nerve stimulation. And very rarely, you need another type of EMG called the single-fiber EMG. On the first situation is, you do not have an antibody, but there is still a high suspicion for myasthenia gravis. For those situations, you do need another test to prove that you have myasthenia gravis. I would say that even if you are positive for LRP4 antibody, you actually need the EMG test to confirm that. Because we have seen a lot of false positive LRP4 antibodies in our practice. So that's number one.

Number two is that, you come to the hospital, and because your myasthenia gravis is relatively severe and rapidly progressive, and you need a very fast diagnosis to start treatment. And remember, these antibodies, most likely, it is a send-out lab, or you can do it locally, but take a few days. It'll take a few days. The EMG can be done tomorrow, the day after tomorrow, and you immediately know the answer whether you have myasthenia gravis or not. So that is the second scenario you might need an antibody test.

The third scenario is even less common. That is, you do have myasthenia gravis and your doctor knows that, but it is unclear whether your symptoms are due to myasthenia gravis or due to something else. Remember, people may have more than one illness, and then you cannot walk, maybe your hip arthritis is causing the problem. So under those situations, even if you know you have myasthenia gravis or even if the doctors know you have myasthenia gravis, they might want to repeat the EMG to make sure that the junction between your nerve and muscle still functions well. So those are the three situations that you might need an EMG.

Glen Stevens, DO, PhD: So back in the old days, we used to do Tensilon tests on patients. I'm not sure they even do that in the hospital anymore, where you're trying to affect the enzyme in the cleft, and allow the acetylcholine to have more effect on the postsynaptic receptor. Sensitive, not helpful or it's really... In the past, we used to use it as a test to determine if they're on too much pyridostigmine or not enough for their crisis, or what direction they're going. Is it helpful for the diagnosis, or not really?

Yuebing Li, MD, PhD: So the Tensilon is no longer produced in the United States since 2018.

Glen Stevens, DO, PhD: So that's why it's not in the hospital anymore.

Yuebing Li, MD, PhD: That's right. It's kind of funny, I think in the year 2021, one of our pharmacists found some Tensilon for me in our CCF pharmacy. So it's traditionally has been viewed as being a very sensitive test. That means that, you have myasthenia gravis, you're more likely being abnormal. But it is a less specific test, that it means that when this test is positive, it really does not mean you truly have myasthenia gravis. So it has been replaced by antibody testing and EMG testing for the diagnosis of myasthenia gravis.

Glen Stevens, DO, PhD: Well, that's interesting. And see, I always learn something in these podcasts. Will it come back, or they just stopped making it? They're not going to-

Yuebing Li, MD, PhD: They just stopped making it.

Glen Stevens, DO, PhD: I've stopped doing the hospital service, but I think when I was on most recently, they were starting to do the ice pack test. I guess, that's the non-invasive way of doing the Tensilon test, where they'd put the ice packs on the eyes, and affect the nerve transmission. Is that helpful?

Yuebing Li, MD, PhD: It is helpful to some extent. It has a similar issue of specificity. I mean, the sensitivity is probably in the 80% range. The specificity, there are different in numbers. We actually just looked at this particular question maybe a month ago, because I reviewed a manuscript. And the sensitivity reported number vary between 50-80%.

Glen Stevens, DO, PhD: Interesting. So we've gone through quite a bit about normal myasthenia gravis, so let's move to seronegative. We'll make the assumption that good lab looked at the results and the antibodies are negative. Tell me what the seronegative myasthenic looks like.

Yuebing Li, MD, PhD: They look exactly the same as acetylcholine receptor antibody-positive myasthenia gravis. So there are a couple of issues here, Glen. One is, you should not just check the antibody once, and that has been proven. When you were initially negative, and you should have repeated the antibody in about 9-12 months. Approximately one in six patients who are initially negative, were turned out to be positive. So that is one thing. The other is, for the seronegative patient, and there is a particular assay called the cell-based assay that has been available in Canada, been available in Europe. That really have not been available in United States, and that can help to detect the low-level antibodies.

Glen Stevens, DO, PhD: Very helpful. So go through the standard treatments for myasthenia gravis, typical versus atypical. And maybe it's the same treatment for the seronegative, but how do we treat patients with MG?

Yuebing Li, MD, PhD: So let's just take the most common type. It would be seropositive patient myasthenia gravis who is either generalized or ocular. The very first medication given is Mestinon or pyridostigmine. And that actually has been approved in the 1950s by FDA as a treatment for myasthenia gravis. It helps almost every subtype of myasthenia gravis except MuSK subtype. The MuSK antibody-positive myasthenia gravis, people can get a lot of side effects or have involuntary movement, and they could be very sensitive to Mestinon. So that's the downside of it.

The problem, and as you alluded to, is myasthenia gravis is an autoimmune disease. And the pyridostigmine or Mestinon doesn't really alter your immune system. It's like when you have a bacteria infection, you get a fever, and you begin to take a Tylenol. You take a Tylenol, your fever's coming down, but the bacteria continues to grow. So people with mild myasthenia gravis, and you start a Mestinon, they may improve, and that's maybe all they need. But a lot of cases, in a lot of cases, you need immunotherapy.

The most common immunotherapy is a steroid, prednisone. And that is typically given starting at relatively high or moderate doses, and then gradually tapered to use the smallest doses to keep your immune system in check. If you are young, and if you are positive for acetylcholine receptor antibody, if you have a general myasthenia gravis, you should be considered for a type of surgery called a thymectomy. You take your thymus gland out. Used to people, the surgeons open the chest. Right now, it's a radioscope surgery, and the patient usually stay in the hospital for two to three days. It's becoming a much smaller, much less invasive surgery nowadays. If you are seronegative, in general, you should not have such a surgery.

Glen Stevens, DO, PhD: My recollection is that sometimes the steroids can worsen the myasthenia or no, initially?

Yuebing Li, MD, PhD: Yeah, there is this observation called corticosteroid dip or steroid-induced exacerbation. So, a little bit of historical information. The steroid was initially given to patients with myasthenia gravis in the 1960s. At that time, almost everybody who had myasthenia gravis, had a pretty significant disease because we did not have good ways of making diagnosis, and only the most obvious ones were given the diagnosis. And when people who have severe symptoms, if you give them relatively high dose steroids and they actually need to be admitted. And in the initial practice is, "Okay, we're ready to give this patient steroids, we need to admit him to the hospital because of the worsening of the myasthenia symptoms." The frequency of steroid dip or corticosteroid dip has dramatically reduced. I would say right now, especially for a patient with relatively mild symptoms, you can start steroids without a worry about steroid-induced exacerbation. In patients with severe symptoms, sometimes you need to either start with a low dose, and escalate a bit, or you start to give some other rapid treatment a little bit, and then bridge it to steroids.

Glen Stevens, DO, PhD: And how long would you treat somebody with steroids generally?

Yuebing Li, MD, PhD: In generally, you should treat a patient for at least six months or longer.

Glen Stevens, DO, PhD: And would you start another immune suppressing medication along with it, or you would look and see what the response is?

Yuebing Li, MD, PhD: That depends on the physician's style. So this is the bottom line, Glen, it's myasthenia gravis is an autoimmune disease. It needs maintenance immunotherapy to keep the disease inactive. The maintenance immunotherapy should be at low dose to protect the human body, to avoid serious side effects. Whether it's a low-dose prednisone, or whether it's a low-dose immunosuppressant. It really depends on the physician's style, the patient's comorbidity, or in preference.

Glen Stevens, DO, PhD: And talk about the use of IVIg or plasma exchange. Is its role really mostly in crisis management, or potentially pre-op for surgery for patients, or does it have a role as maintenance?

Yuebing Li, MD, PhD: So the IVIg had been used as a maintenance therapy for myasthenia gravis, and we still use it. We still use it, and it does work very well for a portion of patients. But with the newer therapies, the use of IVIg becomes less frequent. But it's still one of the two main treatments including IVIg and plasmapheresis for a patient with a crisis. Plasmapheresis has been used for maintenance therapy in the past, for very rare cases. Right now, because of newer therapy, it has been reserved mainly for acute exacerbation, or a patient with myasthenic crisis.

Glen Stevens, DO, PhD: And is there a literature in its use with... Going back to your point that maybe some of the seronegative patients have an antibody that we're not aware of. Is there a literature out there on use of PLEX or IVIg in the seronegative patients?

Yuebing Li, MD, PhD: Yeah, they work equally well.

Glen Stevens, DO, PhD: Yeah, I would think so, right?

Yuebing Li, MD, PhD: Equally well. But there is one special situation that is, in MuSK antibody-positive myasthenia gravis, for some reason, plasmapheresis or PLEX works better than IVIg.

Glen Stevens, DO, PhD: Before we get into the newer medications, standard treatment for the seronegative patients is what?

Yuebing Li, MD, PhD: It's the same.

Glen Stevens, DO, PhD: Is it any different?

Yuebing Li, MD, PhD: No.

Glen Stevens, DO, PhD: Okay, so you would treat the same?

Yuebing Li, MD, PhD: Well, except that you may consider thymectomy less.

Glen Stevens, DO, PhD: Right. So let's move to the newer drugs. I'm glad to see that you have a proliferation of medications, but go through some of the newer medications, mechanism of action, what they're looking at.

Yuebing Li, MD, PhD: So the very first approved immunotherapy for myasthenia gravis was eculizumab. That was approved in 2017. It was a complement inhibitor. Since then, there are two more complement inhibitors that have been approved by FDA. One is ravulizumab, the other is zilucoplan. Eculizumab and ravulizumab are basically cousins, there are only a few amino acid difference. So basically the same drug, except one was given once every two weeks, the other is given once every eight weeks.

Zilucoplan is a small molecule, and it's a subcutaneous injection. Patients can give the injection themselves at home, but it's a daily injection. This kind of therapy works on a complement. And we talk about the myasthenia gravis, it's a disease of neuromuscular junction, it's mostly on the muscle side. The damage of the muscle side is mediated by complement. Not in everybody, but in the majority of the patients with myasthenia gravis. So that's why complement inhibition works for this group of patient. The other class for the newer therapy, there are two. One is efgartigimod, the other is rozanolixizumab.

Glen Stevens, DO, PhD: I'm glad you're saying those.

Yuebing Li, MD, PhD: On these two, basically they're called FcRn therapy. What it does is basically reduce antibody levels in the blood. These two kind of therapies, complement inhibitor therapy and FcRn therapy. They have relatively specific mechanisms, but they don't work on the production of the antibodies. So these therapies need to be combined with other treatments, and if you want to reach remission.

Glen Stevens, DO, PhD: Do you develop antibodies against these monoclonal antibodies, neutralizing antibodies in the body?

Yuebing Li, MD, PhD: You do. These are all humanized monoclonal antibodies. So there are anti-drug antibodies, neutralized antibodies. And so far, it seems to be it only occurs in a small percentage of the patients. The problem though is that these newer agents, they are not effective for everybody. And if you look at all the trials, pivotal trials, as well as real-life experience, I would say approximately 50-60% of patients will respond to one particular therapy. And there is about a 40-50% of patient who only respond.

Glen Stevens, DO, PhD: So I'll go back to a point I made before. Any difference in response with the seronegative patients with these newer medications?

Yuebing Li, MD, PhD: All these newer medications are approved for antibody-positive myasthenia gravis.

Glen Stevens, DO, PhD: So where does that leave you with the seronegative patients?

Yuebing Li, MD, PhD: All right. So, we talk about the five treatments. Among these fives, only the rozanolixizumab has been approved for MuSK antibody-positive myasthenia gravis, as well as acetylcholine receptor antibody-positive myasthenia gravis. The other four were only approved for acetylcholine receptor antibody-positive myasthenia gravis. There were seronegative patients studied in almost every one of these trials, and probably not everyone, but the majority of the trials. The number of the patient was small, and the difference between the drug and the placebo was not sufficient enough. There are efforts right now to conduct trials in seronegative patients. The feeling is that, there are some post-approval experiences suggesting that some of the seronegative patients may also respond to these medications, but larger trial is needed, and there are trials being planned and targeted specifically to antibody-negative myasthenia gravis.

Glen Stevens, DO, PhD: So it looks like you're kind of left with the traditional therapies, acetylcholine receptor, esterase drugs, the immune suppression, PLEX, the IVIg.

Yuebing Li, MD, PhD: Yes.

Glen Stevens, DO, PhD: Talk to me just briefly, what about in cancer, there's been explosion of checkpoint inhibitors and they cause a lot of autoimmune related problems? And one of the autoimmune related problems is myasthenia. You're seeing much of that?

Yuebing Li, MD, PhD: We see a lot. Actually, we were the... The very first patient I saw was in 2015. We actually published one of the very first cases of pembrolizumab-induced myasthenia gravis. It's a tough group. It's a tough group, I can tell you, for several reasons. Number one, these are all patients with severe symptoms, very rapid, and they're very severe symptoms. The very first one, I saw the patient in the office. Before she showed up, she already had a feeding tube placed. The second is that only about half of these patient are antibody positive.

Glen Stevens, DO, PhD: I was going to ask you what percent are antibody positive?

Yuebing Li, MD, PhD: One in five. The third is, you know this patient has myasthenia gravis. Sometimes the sensitivity of EMG is not very high either, so it makes it tough to make a diagnosis. The fourth is, these drugs does not only affect the neuromuscular junction, sometimes they affect the nerves, sometimes it affects the muscle. Sometimes it affects the heart. So we see these people have weakness, we know it's a peripheral nervous system. Sometimes we have a hard time to decide, is this the myositis or muscle problem? Is this myasthenia gravis neuromuscular junction problem? Or this is a Guillain-Barré, like a motor nerve problem. Sometimes, a patient may have all three. So the complexity make it hard to treat.

Glen Stevens, DO, PhD: Well, I'm glad you're looking after these, Yuebing. Anything that we haven't discussed that you think it's important for our listeners to hear?

Yuebing Li, MD, PhD: Well, a couple of points. One is, we mainly talked about general myasthenia gravis, but the ocular myasthenia gravis accounted for, and I would say, at least a half, probably have even majority of the patients with myasthenia gravis. Unfortunately, all the newer drugs we talk about do not cover ocular myasthenia gravis.

Glen Stevens, DO, PhD: Meaning they don't have a benefit, or they're not approved?

Yuebing Li, MD, PhD: They're not approved. But luckily, one of the pharmaceutical companies is initiating a trial on ocular myasthenia gravis. And traditionally, we talk about ocular myasthenia gravis accounted for 15% of patients. And right now, I think that the diagnostic tool, it's better in patient... Doctors realize these conditions faster, so we make a lot of early diagnosis. Because right now, ocular myasthenia gravis probably accounting for about half of the myasthenia gravis patient. So that is number one.

Number two is, we need treatment for patients with myasthenic crisis, or the patient with very severe myasthenia gravis that has been admitted to the hospital. The problem with these newer therapies, they are very expensive. And for a lot of hospitals, Cleveland Clinic the same way, is that they are approved for outpatient therapy, they are not approved for inpatient therapy. But the onset of the efficacy for these drugs, they're very quick. They can be a few days or a week or two, and they may be a little bit slower than IVIg or plasmapheresis, but another much slower. IVIg and plasmapheresis only works for about 70% of people. And there are people who are on a ventilator, probably they could respond to this medication. So there is a need to study these patients with very severe myasthenia gravis or myasthenic crisis using these new therapies.

Glen Stevens, DO, PhD: Well, Yuebing, it's been very enlightening as always. I'm glad to see, what'd you say? There's five new medications out, and more to come. So an embarrassment of riches has come your way, and now you need to figure out exactly how you can work the system to get the drugs to the patients that need to have them. So-

Yuebing Li, MD, PhD: It's a good problem.

Glen Stevens, DO, PhD: Yeah, it's a better problem to have. So, appreciate it, and looking forward to having you come back and tell us how you're going to solve crisis for these patients as well.

Yuebing Li, MD, PhD: Thank you. Thanks for having me.

Closing: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's @CleClinicMD, all one word. And thank you for listening.