Nicholas J. Silvestri, MD

Nicholas J. Silvestri, MD: Hi there. My name is Dr Nick Silvestri, and I'm at the University of Buffalo. Today, I'd like to answer a few questions that I commonly receive from colleagues about the treatment of myasthenia gravis. As you know, over the past several years, we've had many new treatments approved to treat myasthenia gravis. One of the common questions that I get is, how do these new treatments fit into my treatment paradigm? 

First and foremost, I'd like to say that we've been very successful at treating myasthenia gravis for many years. The mainstay of therapy has typically been acetylcholinesterase inhibitors, corticosteroids, and nonsteroidal immunosuppressants. These medicines by and large have helped control the disease in many, but maybe not all, patients. 

The good news about these treatments is they're very efficacious, and as I said, they are able to treat most patients with myasthenia gravis. But the bad news on these medications is that they can have some serious short- and long-term consequences. So as I think about the treatment paradigm right now in 2024 and treating patients with myasthenia gravis, I typically start with prednisone or corticosteroids and transition patients onto an oral immunosuppressant. 

But because it takes about a year for those oral immunosuppressants to become effective, I'm typically using steroids as a bridge. The goal, really, is to have patients on an oral immunosuppressant alone at the 1-year mark or thereabouts so that we don't have patients on steroids. 

When it comes to the new therapies, one of the things that I'm doing is I'm using them, if a patient does not respond to an oral immunosuppressant or in situations where patients have medical comorbidities that make me not want to use steroids or use steroids at high doses. 

Specifically, FcRn antagonists are often used as next-line therapy after an oral immunosuppressant fails or if I don't feel comfortable using prednisone at the outset and possibly bringing the patient to the oral immunosuppressant. The rationale behind this is that these medications are effective. They've been shown to be effective in clinical trials. They work fairly quickly, usually within 2-4 weeks. They're convenient for patients. And they have a pretty good safety profile. 

The major side effects with the FcRn antagonists tend to be an increased risk for infection, which is true for most medications used to treat myasthenia gravis. One is associated with headache. And they can be associated with joint pains and infusion issues as well. But by and large, they are well tolerated. So again, if a patient is not responding to an oral immunosuppressant or it has toxicity or side effects, or I'm leery of using prednisone, I'll typically use an FcRn antagonist. 

The other main class of medications is complement inhibitors. There are three complement inhibitors approved to use in the United States. Complement inhibitors are also very effective medications. I've used them with success in a number of patients, and I think that the paradigm is shifting. 

I've used complement inhibitors, as with the FcRn antagonists, in patients who aren't responding to the first line of therapy or if they have toxicity. I've also used complement inhibitors in instances where patients have not responded very robustly to FcRn antagonists, which thankfully is the minority of patients, but it's worth noting. 

I view the treatment paradigm for 2024 as oral immunosuppressant first, then FcRn antagonist next, and then complement inhibitor next. But to be truthful, we don't have head-to-head comparisons right now. What works for one patient may not work for another. In myasthenia gravis, it would be great to have biomarkers that allow us to predict who would respond to what form of therapy better. 

In other words, it would be great to be able to send off a test to know whether a patient would respond to an oral immunosuppressant better than perhaps to one of the newer therapies, or whether a patient would respond to an FcRn antagonist better than a complement inhibitor or vice versa. That's really one of the gold standards or holy grails in the treatment of myasthenia gravis. 

Another thing that comes up in relation to the first question has to do with, what patient characteristics do I keep in mind when selecting therapies? There's a couple of things. I think that first and foremost, many of our patients with myasthenia gravis are women of childbearing age. So we want to be mindful that many pregnancies are not planned, and be careful when we're choosing therapies that might have a role or might be deleterious to fetuses. 

This is particularly true with oral immunosuppressants, many of which are contraindicated in pregnancy. But medical comorbidities in general are helpful to understand. Again, using the corticosteroid example, in patients with high blood pressure, diabetes, or osteoporosis, I'm very leery about corticosteroids and may use one of the newer therapies earlier on. 

Another aspect is patient preference. We have oral therapies, we have intravenous therapies, we now have subcutaneous therapies. Route of administration is very important to consider as well, not only for patient comfort — some patients may prefer intravenous routes of administration vs subcutaneous — but also for patient convenience. 

Many of our patients with myasthenia gravis have very busy lives, with full-time jobs and other responsibilities, such as parenting or taking care of parents that are maybe older in age. So I think that tolerability and convenience are very important to getting patients the therapies they need and allowing patients the flexibility and convenience to be able to live their lives as well. 

I hope this was helpful to you. I look forward to speaking with you again at some point in the very near future. Stay well. 

Nicholas J. Silvestri, MD: Hi there. My name is Dr Nick Silvestri, and I'm at the University of Buffalo. Today, I'd like to answer a few questions that I commonly receive from colleagues about the treatment of myasthenia gravis. As you know, over the past several years, we've had many new treatments approved to treat myasthenia gravis. One of the common questions that I get is, how do these new treatments fit into my treatment paradigm? 

First and foremost, I'd like to say that we've been very successful at treating myasthenia gravis for many years. The mainstay of therapy has typically been acetylcholinesterase inhibitors, corticosteroids, and nonsteroidal immunosuppressants. These medicines by and large have helped control the disease in many, but maybe not all, patients. 

The good news about these treatments is they're very efficacious, and as I said, they are able to treat most patients with myasthenia gravis. But the bad news on these medications is that they can have some serious short- and long-term consequences. So as I think about the treatment paradigm right now in 2024 and treating patients with myasthenia gravis, I typically start with prednisone or corticosteroids and transition patients onto an oral immunosuppressant. 

But because it takes about a year for those oral immunosuppressants to become effective, I'm typically using steroids as a bridge. The goal, really, is to have patients on an oral immunosuppressant alone at the 1-year mark or thereabouts so that we don't have patients on steroids. 

When it comes to the new therapies, one of the things that I'm doing is I'm using them, if a patient does not respond to an oral immunosuppressant or in situations where patients have medical comorbidities that make me not want to use steroids or use steroids at high doses. 

Specifically, FcRn antagonists are often used as next-line therapy after an oral immunosuppressant fails or if I don't feel comfortable using prednisone at the outset and possibly bringing the patient to the oral immunosuppressant. The rationale behind this is that these medications are effective. They've been shown to be effective in clinical trials. They work fairly quickly, usually within 2-4 weeks. They're convenient for patients. And they have a pretty good safety profile. 

The major side effects with the FcRn antagonists tend to be an increased risk for infection, which is true for most medications used to treat myasthenia gravis. One is associated with headache. And they can be associated with joint pains and infusion issues as well. But by and large, they are well tolerated. So again, if a patient is not responding to an oral immunosuppressant or it has toxicity or side effects, or I'm leery of using prednisone, I'll typically use an FcRn antagonist. 

The other main class of medications is complement inhibitors. There are three complement inhibitors approved to use in the United States. Complement inhibitors are also very effective medications. I've used them with success in a number of patients, and I think that the paradigm is shifting. 

I've used complement inhibitors, as with the FcRn antagonists, in patients who aren't responding to the first line of therapy or if they have toxicity. I've also used complement inhibitors in instances where patients have not responded very robustly to FcRn antagonists, which thankfully is the minority of patients, but it's worth noting. 

I view the treatment paradigm for 2024 as oral immunosuppressant first, then FcRn antagonist next, and then complement inhibitor next. But to be truthful, we don't have head-to-head comparisons right now. What works for one patient may not work for another. In myasthenia gravis, it would be great to have biomarkers that allow us to predict who would respond to what form of therapy better. 

In other words, it would be great to be able to send off a test to know whether a patient would respond to an oral immunosuppressant better than perhaps to one of the newer therapies, or whether a patient would respond to an FcRn antagonist better than a complement inhibitor or vice versa. That's really one of the gold standards or holy grails in the treatment of myasthenia gravis. 

Another thing that comes up in relation to the first question has to do with, what patient characteristics do I keep in mind when selecting therapies? There's a couple of things. I think that first and foremost, many of our patients with myasthenia gravis are women of childbearing age. So we want to be mindful that many pregnancies are not planned, and be careful when we're choosing therapies that might have a role or might be deleterious to fetuses. 

This is particularly true with oral immunosuppressants, many of which are contraindicated in pregnancy. But medical comorbidities in general are helpful to understand. Again, using the corticosteroid example, in patients with high blood pressure, diabetes, or osteoporosis, I'm very leery about corticosteroids and may use one of the newer therapies earlier on. 

Another aspect is patient preference. We have oral therapies, we have intravenous therapies, we now have subcutaneous therapies. Route of administration is very important to consider as well, not only for patient comfort — some patients may prefer intravenous routes of administration vs subcutaneous — but also for patient convenience. 

Many of our patients with myasthenia gravis have very busy lives, with full-time jobs and other responsibilities, such as parenting or taking care of parents that are maybe older in age. So I think that tolerability and convenience are very important to getting patients the therapies they need and allowing patients the flexibility and convenience to be able to live their lives as well. 

I hope this was helpful to you. I look forward to speaking with you again at some point in the very near future. Stay well. 

Nicholas J. Silvestri, MD: Hi there. My name is Dr Nick Silvestri, and I'm at the University of Buffalo. Today, I'd like to answer a few questions that I commonly receive from colleagues about the treatment of myasthenia gravis. As you know, over the past several years, we've had many new treatments approved to treat myasthenia gravis. One of the common questions that I get is, how do these new treatments fit into my treatment paradigm? 

First and foremost, I'd like to say that we've been very successful at treating myasthenia gravis for many years. The mainstay of therapy has typically been acetylcholinesterase inhibitors, corticosteroids, and nonsteroidal immunosuppressants. These medicines by and large have helped control the disease in many, but maybe not all, patients. 

The good news about these treatments is they're very efficacious, and as I said, they are able to treat most patients with myasthenia gravis. But the bad news on these medications is that they can have some serious short- and long-term consequences. So as I think about the treatment paradigm right now in 2024 and treating patients with myasthenia gravis, I typically start with prednisone or corticosteroids and transition patients onto an oral immunosuppressant. 

But because it takes about a year for those oral immunosuppressants to become effective, I'm typically using steroids as a bridge. The goal, really, is to have patients on an oral immunosuppressant alone at the 1-year mark or thereabouts so that we don't have patients on steroids. 

When it comes to the new therapies, one of the things that I'm doing is I'm using them, if a patient does not respond to an oral immunosuppressant or in situations where patients have medical comorbidities that make me not want to use steroids or use steroids at high doses. 

Specifically, FcRn antagonists are often used as next-line therapy after an oral immunosuppressant fails or if I don't feel comfortable using prednisone at the outset and possibly bringing the patient to the oral immunosuppressant. The rationale behind this is that these medications are effective. They've been shown to be effective in clinical trials. They work fairly quickly, usually within 2-4 weeks. They're convenient for patients. And they have a pretty good safety profile. 

The major side effects with the FcRn antagonists tend to be an increased risk for infection, which is true for most medications used to treat myasthenia gravis. One is associated with headache. And they can be associated with joint pains and infusion issues as well. But by and large, they are well tolerated. So again, if a patient is not responding to an oral immunosuppressant or it has toxicity or side effects, or I'm leery of using prednisone, I'll typically use an FcRn antagonist. 

The other main class of medications is complement inhibitors. There are three complement inhibitors approved to use in the United States. Complement inhibitors are also very effective medications. I've used them with success in a number of patients, and I think that the paradigm is shifting. 

I've used complement inhibitors, as with the FcRn antagonists, in patients who aren't responding to the first line of therapy or if they have toxicity. I've also used complement inhibitors in instances where patients have not responded very robustly to FcRn antagonists, which thankfully is the minority of patients, but it's worth noting. 

I view the treatment paradigm for 2024 as oral immunosuppressant first, then FcRn antagonist next, and then complement inhibitor next. But to be truthful, we don't have head-to-head comparisons right now. What works for one patient may not work for another. In myasthenia gravis, it would be great to have biomarkers that allow us to predict who would respond to what form of therapy better. 

In other words, it would be great to be able to send off a test to know whether a patient would respond to an oral immunosuppressant better than perhaps to one of the newer therapies, or whether a patient would respond to an FcRn antagonist better than a complement inhibitor or vice versa. That's really one of the gold standards or holy grails in the treatment of myasthenia gravis. 

Another thing that comes up in relation to the first question has to do with, what patient characteristics do I keep in mind when selecting therapies? There's a couple of things. I think that first and foremost, many of our patients with myasthenia gravis are women of childbearing age. So we want to be mindful that many pregnancies are not planned, and be careful when we're choosing therapies that might have a role or might be deleterious to fetuses. 

This is particularly true with oral immunosuppressants, many of which are contraindicated in pregnancy. But medical comorbidities in general are helpful to understand. Again, using the corticosteroid example, in patients with high blood pressure, diabetes, or osteoporosis, I'm very leery about corticosteroids and may use one of the newer therapies earlier on. 

Another aspect is patient preference. We have oral therapies, we have intravenous therapies, we now have subcutaneous therapies. Route of administration is very important to consider as well, not only for patient comfort — some patients may prefer intravenous routes of administration vs subcutaneous — but also for patient convenience. 

Many of our patients with myasthenia gravis have very busy lives, with full-time jobs and other responsibilities, such as parenting or taking care of parents that are maybe older in age. So I think that tolerability and convenience are very important to getting patients the therapies they need and allowing patients the flexibility and convenience to be able to live their lives as well. 

I hope this was helpful to you. I look forward to speaking with you again at some point in the very near future. Stay well. 

Clinical advances in myasthenia gravis from the 2023 American Academy of Neurology (AAN) Annual Meeting include the association between fatigue and disease severity and promising results from three ongoing trials of novel therapies, as reported by Dr Nicholas Silvestri, from the University at Buffalo, Buffalo, New York. 

Dr Silvestri begins by discussing a study of autoantibodies in patients with seronegative disease, which highlighted the potential for impaired B-cell tolerance, and goes on to examine research underscoring the association between fatigue and disease severity, as well as anxiety and depression. 

Moving on to novel therapies, Dr Silvestri reviews a combined analysis of three trials of rozanolixizumab, which demonstrated the drug's encouraging efficacy and favorable safety profile. 

Next, he turns to the ADAPT+ trial, which showed that efgartigimod continued to have an improved clinical response after patients rolled over from the initial ADAPT trial to ADAPT+, with no new safety signals apparent. 

Finally, Dr Silvestri looks at data from the postmarketing registry of eculizumab, which revealed how a significant proportion of patients were able discontinue or reduce their other medications once they started the drug. 

--

Nicholas J. Silvestri, MD, Associate Professor, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York 

Nicholas J. Silvestri, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: argenx; Alexion; Immunovant; UCB 

Serve(d) as a speaker or a member of a speakers bureau for: argenx; Alexion 

Clinical advances in myasthenia gravis from the 2023 American Academy of Neurology (AAN) Annual Meeting include the association between fatigue and disease severity and promising results from three ongoing trials of novel therapies, as reported by Dr Nicholas Silvestri, from the University at Buffalo, Buffalo, New York. 

Dr Silvestri begins by discussing a study of autoantibodies in patients with seronegative disease, which highlighted the potential for impaired B-cell tolerance, and goes on to examine research underscoring the association between fatigue and disease severity, as well as anxiety and depression. 

Moving on to novel therapies, Dr Silvestri reviews a combined analysis of three trials of rozanolixizumab, which demonstrated the drug's encouraging efficacy and favorable safety profile. 

Next, he turns to the ADAPT+ trial, which showed that efgartigimod continued to have an improved clinical response after patients rolled over from the initial ADAPT trial to ADAPT+, with no new safety signals apparent. 

Finally, Dr Silvestri looks at data from the postmarketing registry of eculizumab, which revealed how a significant proportion of patients were able discontinue or reduce their other medications once they started the drug. 

--

Nicholas J. Silvestri, MD, Associate Professor, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York 

Nicholas J. Silvestri, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: argenx; Alexion; Immunovant; UCB 

Serve(d) as a speaker or a member of a speakers bureau for: argenx; Alexion 

Clinical advances in myasthenia gravis from the 2023 American Academy of Neurology (AAN) Annual Meeting include the association between fatigue and disease severity and promising results from three ongoing trials of novel therapies, as reported by Dr Nicholas Silvestri, from the University at Buffalo, Buffalo, New York. 

Dr Silvestri begins by discussing a study of autoantibodies in patients with seronegative disease, which highlighted the potential for impaired B-cell tolerance, and goes on to examine research underscoring the association between fatigue and disease severity, as well as anxiety and depression. 

Moving on to novel therapies, Dr Silvestri reviews a combined analysis of three trials of rozanolixizumab, which demonstrated the drug's encouraging efficacy and favorable safety profile. 

Next, he turns to the ADAPT+ trial, which showed that efgartigimod continued to have an improved clinical response after patients rolled over from the initial ADAPT trial to ADAPT+, with no new safety signals apparent. 

Finally, Dr Silvestri looks at data from the postmarketing registry of eculizumab, which revealed how a significant proportion of patients were able discontinue or reduce their other medications once they started the drug. 

--

Nicholas J. Silvestri, MD, Associate Professor, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York 

Nicholas J. Silvestri, MD, has disclosed the following relevant financial relationships: 

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: argenx; Alexion; Immunovant; UCB 

Serve(d) as a speaker or a member of a speakers bureau for: argenx; Alexion