Jim Kling

CHICAGO — Have a great tech idea to improve gastroenterology? Start-up companies have the potential to transform the practice of medicine, and to make founders a nice pot of money, but it is a difficult road. At the 2024 AGA Tech Summit, held at the Chicago headquarters of MATTER, a global healthcare startup incubator, investors and gastroenterologists discussed some of the key challenges and opportunities for GI startups.

The road is daunting, and founders must be dedicated to their companies but also maintain life balance. “It is very easy, following your passion, for your life to get out of check. I don’t know what the divorce rate is for entrepreneurs, but I personally was a victim of that. The culture that we built was addictive and it became all encompassing, and at the same time [I neglected] my home life,” Scott Fraser, managing director of the consulting company Fraser Healthcare, said during a “Scars and Stripes” panel at the summit.

Barry M. Hertzberg

For those willing to navigate those waters, there is help. Investors are prepared to provide seed money for companies with good ideas and a strong market. AGA itself has stepped into the investment field with its GI Opportunity Fund, which it launched in 2022 through a partnership with Varia Ventures. The fund’s capital comes from AGA members, with a minimum investment of $25,000. To date, AGA has made investments in six companies, at around $100,000 per company. “It’s not a large amount that we’re investing. We’re a lead investor that signals to other venture capital companies that this is a viable company,” Tom Serena, CEO of AGA, said in an interview.

The fund grew out of AGA’s commitment to boosting early-stage companies in the gastroenterology space. AGA has always supported GI device and tech companies through its Center for GI Innovation and Technology, which sponsored the AGA Tech Summit. The center now provides resources and advice for GI innovators and startups. The AGA Tech Summit has created a gathering place for entrepreneurs and innovators to share their experiences and learn from one another. “But what we were missing was the last mile, which is getting funding to the companies,” said Mr. Serena. The summit itself has been modified to increase the venture capital presence. “That’s the networking we’re trying to [create] here. Venture capitalists are well acquainted with these companies, but we feel that AGA can bring clinical due diligence, and the startups want to be exposed to venture capital,” said Mr. Serena.

During the “Learn from VC Strategists” panel, investors shared advice for entrepreneurs. The emphasis throughout was on marketable ideas that can fundamentally change healthcare practice, though inventions may not have the whiz-bang appeal of some new technologies of years past.

“We’re particularly focused on clinical models that actually work. There were a lot of companies for many years that were doing things that had minimal impact, or very incremental impact. Maybe they were helping identify certain patients, but they weren’t actually engaging those patients. We’re now looking very end-to-end and trying to make sure that it’s not just a good idea, but one that you can actually roll out, engage patients, and see the [return on investment] in that patient data,” said Kelsey Maguire, managing director of the Blue Venture Fund, which is a collaborative effort across Blue Cross Blue Shield companies.

Blue Venture Fund

AGA

Karen L. Richard Photography

Arboretum Ventures

CHICAGO — Have a great tech idea to improve gastroenterology? Start-up companies have the potential to transform the practice of medicine, and to make founders a nice pot of money, but it is a difficult road. At the 2024 AGA Tech Summit, held at the Chicago headquarters of MATTER, a global healthcare startup incubator, investors and gastroenterologists discussed some of the key challenges and opportunities for GI startups.

The road is daunting, and founders must be dedicated to their companies but also maintain life balance. “It is very easy, following your passion, for your life to get out of check. I don’t know what the divorce rate is for entrepreneurs, but I personally was a victim of that. The culture that we built was addictive and it became all encompassing, and at the same time [I neglected] my home life,” Scott Fraser, managing director of the consulting company Fraser Healthcare, said during a “Scars and Stripes” panel at the summit.

Barry M. Hertzberg

For those willing to navigate those waters, there is help. Investors are prepared to provide seed money for companies with good ideas and a strong market. AGA itself has stepped into the investment field with its GI Opportunity Fund, which it launched in 2022 through a partnership with Varia Ventures. The fund’s capital comes from AGA members, with a minimum investment of $25,000. To date, AGA has made investments in six companies, at around $100,000 per company. “It’s not a large amount that we’re investing. We’re a lead investor that signals to other venture capital companies that this is a viable company,” Tom Serena, CEO of AGA, said in an interview.

The fund grew out of AGA’s commitment to boosting early-stage companies in the gastroenterology space. AGA has always supported GI device and tech companies through its Center for GI Innovation and Technology, which sponsored the AGA Tech Summit. The center now provides resources and advice for GI innovators and startups. The AGA Tech Summit has created a gathering place for entrepreneurs and innovators to share their experiences and learn from one another. “But what we were missing was the last mile, which is getting funding to the companies,” said Mr. Serena. The summit itself has been modified to increase the venture capital presence. “That’s the networking we’re trying to [create] here. Venture capitalists are well acquainted with these companies, but we feel that AGA can bring clinical due diligence, and the startups want to be exposed to venture capital,” said Mr. Serena.

During the “Learn from VC Strategists” panel, investors shared advice for entrepreneurs. The emphasis throughout was on marketable ideas that can fundamentally change healthcare practice, though inventions may not have the whiz-bang appeal of some new technologies of years past.

“We’re particularly focused on clinical models that actually work. There were a lot of companies for many years that were doing things that had minimal impact, or very incremental impact. Maybe they were helping identify certain patients, but they weren’t actually engaging those patients. We’re now looking very end-to-end and trying to make sure that it’s not just a good idea, but one that you can actually roll out, engage patients, and see the [return on investment] in that patient data,” said Kelsey Maguire, managing director of the Blue Venture Fund, which is a collaborative effort across Blue Cross Blue Shield companies.

Blue Venture Fund

AGA

Karen L. Richard Photography

Arboretum Ventures

CHICAGO — Have a great tech idea to improve gastroenterology? Start-up companies have the potential to transform the practice of medicine, and to make founders a nice pot of money, but it is a difficult road. At the 2024 AGA Tech Summit, held at the Chicago headquarters of MATTER, a global healthcare startup incubator, investors and gastroenterologists discussed some of the key challenges and opportunities for GI startups.

The road is daunting, and founders must be dedicated to their companies but also maintain life balance. “It is very easy, following your passion, for your life to get out of check. I don’t know what the divorce rate is for entrepreneurs, but I personally was a victim of that. The culture that we built was addictive and it became all encompassing, and at the same time [I neglected] my home life,” Scott Fraser, managing director of the consulting company Fraser Healthcare, said during a “Scars and Stripes” panel at the summit.

Barry M. Hertzberg

For those willing to navigate those waters, there is help. Investors are prepared to provide seed money for companies with good ideas and a strong market. AGA itself has stepped into the investment field with its GI Opportunity Fund, which it launched in 2022 through a partnership with Varia Ventures. The fund’s capital comes from AGA members, with a minimum investment of $25,000. To date, AGA has made investments in six companies, at around $100,000 per company. “It’s not a large amount that we’re investing. We’re a lead investor that signals to other venture capital companies that this is a viable company,” Tom Serena, CEO of AGA, said in an interview.

The fund grew out of AGA’s commitment to boosting early-stage companies in the gastroenterology space. AGA has always supported GI device and tech companies through its Center for GI Innovation and Technology, which sponsored the AGA Tech Summit. The center now provides resources and advice for GI innovators and startups. The AGA Tech Summit has created a gathering place for entrepreneurs and innovators to share their experiences and learn from one another. “But what we were missing was the last mile, which is getting funding to the companies,” said Mr. Serena. The summit itself has been modified to increase the venture capital presence. “That’s the networking we’re trying to [create] here. Venture capitalists are well acquainted with these companies, but we feel that AGA can bring clinical due diligence, and the startups want to be exposed to venture capital,” said Mr. Serena.

During the “Learn from VC Strategists” panel, investors shared advice for entrepreneurs. The emphasis throughout was on marketable ideas that can fundamentally change healthcare practice, though inventions may not have the whiz-bang appeal of some new technologies of years past.

“We’re particularly focused on clinical models that actually work. There were a lot of companies for many years that were doing things that had minimal impact, or very incremental impact. Maybe they were helping identify certain patients, but they weren’t actually engaging those patients. We’re now looking very end-to-end and trying to make sure that it’s not just a good idea, but one that you can actually roll out, engage patients, and see the [return on investment] in that patient data,” said Kelsey Maguire, managing director of the Blue Venture Fund, which is a collaborative effort across Blue Cross Blue Shield companies.

Blue Venture Fund

AGA

Karen L. Richard Photography

Arboretum Ventures

NASHVILLE, TENNESSEE — Multiple sclerosis (MS) is much more commonly diagnosed in women, but men get the diagnosis too and can present some special challenges to disease management and treatment. Disease course, mental health, and social function may be different in male patients.

Among the clinical differences: Men may be diagnosed at an older age, often closer to 30 years of age, and they more often experience memory problems, spinal cord lesions, and motor symptoms. They are at higher risk of progressive-onset disease, but have lower relapse rates. Disability rates are higher in men than in women, but long-term survival is no different. Brain atrophy is also more common among men.

Not all MRI facilities will include brain atrophy assessment, so it is a good idea to put an order in for brain atrophy when there are reasons to be concerned, such as cognitive effects or issues with walking, according to Jeffrey Hernandez, DNP, during a talk at the annual meeting of the Consortium of Multiple Sclerosis Centers. Dr. Hernandez is affiliated with the University of Miami Multiple Sclerosis Center.
 

Addressing Sensitive Topics

Men may be less willing to discuss their symptoms, in part because they may have been raised to be tough and stoic. “Looking for help might make them feel more vulnerable,” said Dr. Hernandez. That’s not a feeling that most men are familiar with, he said. Men “don’t want to be deemed or seem weak or dependent on anyone.” Consequently, men are less likely to complain about any symptom, said Dr. Hernandez.

He advised asking more open-ended questions in an effort to draw men out. “Just ask how they’re doing. See if anything has changed from their usual habits, have their activities of daily living changed, has their work performance changed? That can give you an indication. One of my patients [said he] was demoted from [his] position, that the demotion was related to cognitive impairment and the way that he was working. That gives you an idea as to where you can help intervene and perhaps make an improvement for that patient’s quality of life, or consider switching treatments,” said Dr. Hernandez.

Men are less likely to report symptoms such as tingling, physical complaints, cognitive difficulties, mood changes, and sexual dysfunction. That doesn’t mean they’re not experiencing issues, though, especially when it comes to sexual problems. Dr. Hernandez recalled one patient who just stared out the window when asked about his sex life. “Then I said, the next time I want your wife to be here, and then she spilled the beans on everything. So it’s important sometimes to include other members of the family or their partners in the conversation to give you some insight. And perhaps that day it wasn’t a priority for him, but then the next time it was a priority for his wife,” he said.

He pointed out that erectile dysfunction could be due to a physiological response to MS, or to psychological effects.

Low testosterone levels may also play a role in MS, since it is a natural anti-inflammatory hormone. Hypogonadism has been found to be high among men with MS in some studies. MS in men is associated with more enhancing lesions, greater cognitive decline, and increased risk of disability, while high levels of testosterone are linked to neuroprotective effects and lower risk of developing MS.

Men with MS are more likely than women to report suicidal thoughts when depressed, and mental health can be taboo, as men may try to solve problems on their own before seeking help. “But a lot of the times they can use a little bit of help, whether it be from talk therapy or meds. With the expansion of telemedicine, virtual care has skyrocketed in psychiatry. I advocate strongly for it. Psychologytoday.com is a very common portal that I recommend so they can look up providers with their insurances, and they can see who gives in person versus virtual care. They can do it from the comfort of their car. I’ve had people in their car crying because they don’t want to be in their house when they talk to me,” said Dr. Hernandez.

Physical struggles can lead men to feel they’ve lost their independence, and that they are no longer the protector of the household. Divorce is common, which can lead to social isolation. One patient wanted to see Dr. Hernandez monthly, a request that he had to decline. “Sometimes they want to discuss these things and they just don’t have someone to talk to,” said Dr. Hernandez. Social support programs through the National MS Society, the MS Foundation, or the Multiple Sclerosis Association of America may sponsor local programs that could be beneficial.

Dr. Hernandez has no relevant financial disclosures.

NASHVILLE, TENNESSEE — Multiple sclerosis (MS) is much more commonly diagnosed in women, but men get the diagnosis too and can present some special challenges to disease management and treatment. Disease course, mental health, and social function may be different in male patients.

Among the clinical differences: Men may be diagnosed at an older age, often closer to 30 years of age, and they more often experience memory problems, spinal cord lesions, and motor symptoms. They are at higher risk of progressive-onset disease, but have lower relapse rates. Disability rates are higher in men than in women, but long-term survival is no different. Brain atrophy is also more common among men.

Not all MRI facilities will include brain atrophy assessment, so it is a good idea to put an order in for brain atrophy when there are reasons to be concerned, such as cognitive effects or issues with walking, according to Jeffrey Hernandez, DNP, during a talk at the annual meeting of the Consortium of Multiple Sclerosis Centers. Dr. Hernandez is affiliated with the University of Miami Multiple Sclerosis Center.
 

Addressing Sensitive Topics

Men may be less willing to discuss their symptoms, in part because they may have been raised to be tough and stoic. “Looking for help might make them feel more vulnerable,” said Dr. Hernandez. That’s not a feeling that most men are familiar with, he said. Men “don’t want to be deemed or seem weak or dependent on anyone.” Consequently, men are less likely to complain about any symptom, said Dr. Hernandez.

He advised asking more open-ended questions in an effort to draw men out. “Just ask how they’re doing. See if anything has changed from their usual habits, have their activities of daily living changed, has their work performance changed? That can give you an indication. One of my patients [said he] was demoted from [his] position, that the demotion was related to cognitive impairment and the way that he was working. That gives you an idea as to where you can help intervene and perhaps make an improvement for that patient’s quality of life, or consider switching treatments,” said Dr. Hernandez.

Men are less likely to report symptoms such as tingling, physical complaints, cognitive difficulties, mood changes, and sexual dysfunction. That doesn’t mean they’re not experiencing issues, though, especially when it comes to sexual problems. Dr. Hernandez recalled one patient who just stared out the window when asked about his sex life. “Then I said, the next time I want your wife to be here, and then she spilled the beans on everything. So it’s important sometimes to include other members of the family or their partners in the conversation to give you some insight. And perhaps that day it wasn’t a priority for him, but then the next time it was a priority for his wife,” he said.

He pointed out that erectile dysfunction could be due to a physiological response to MS, or to psychological effects.

Low testosterone levels may also play a role in MS, since it is a natural anti-inflammatory hormone. Hypogonadism has been found to be high among men with MS in some studies. MS in men is associated with more enhancing lesions, greater cognitive decline, and increased risk of disability, while high levels of testosterone are linked to neuroprotective effects and lower risk of developing MS.

Men with MS are more likely than women to report suicidal thoughts when depressed, and mental health can be taboo, as men may try to solve problems on their own before seeking help. “But a lot of the times they can use a little bit of help, whether it be from talk therapy or meds. With the expansion of telemedicine, virtual care has skyrocketed in psychiatry. I advocate strongly for it. Psychologytoday.com is a very common portal that I recommend so they can look up providers with their insurances, and they can see who gives in person versus virtual care. They can do it from the comfort of their car. I’ve had people in their car crying because they don’t want to be in their house when they talk to me,” said Dr. Hernandez.

Physical struggles can lead men to feel they’ve lost their independence, and that they are no longer the protector of the household. Divorce is common, which can lead to social isolation. One patient wanted to see Dr. Hernandez monthly, a request that he had to decline. “Sometimes they want to discuss these things and they just don’t have someone to talk to,” said Dr. Hernandez. Social support programs through the National MS Society, the MS Foundation, or the Multiple Sclerosis Association of America may sponsor local programs that could be beneficial.

Dr. Hernandez has no relevant financial disclosures.

NASHVILLE, TENNESSEE — Multiple sclerosis (MS) is much more commonly diagnosed in women, but men get the diagnosis too and can present some special challenges to disease management and treatment. Disease course, mental health, and social function may be different in male patients.

Among the clinical differences: Men may be diagnosed at an older age, often closer to 30 years of age, and they more often experience memory problems, spinal cord lesions, and motor symptoms. They are at higher risk of progressive-onset disease, but have lower relapse rates. Disability rates are higher in men than in women, but long-term survival is no different. Brain atrophy is also more common among men.

Not all MRI facilities will include brain atrophy assessment, so it is a good idea to put an order in for brain atrophy when there are reasons to be concerned, such as cognitive effects or issues with walking, according to Jeffrey Hernandez, DNP, during a talk at the annual meeting of the Consortium of Multiple Sclerosis Centers. Dr. Hernandez is affiliated with the University of Miami Multiple Sclerosis Center.
 

Addressing Sensitive Topics

Men may be less willing to discuss their symptoms, in part because they may have been raised to be tough and stoic. “Looking for help might make them feel more vulnerable,” said Dr. Hernandez. That’s not a feeling that most men are familiar with, he said. Men “don’t want to be deemed or seem weak or dependent on anyone.” Consequently, men are less likely to complain about any symptom, said Dr. Hernandez.

He advised asking more open-ended questions in an effort to draw men out. “Just ask how they’re doing. See if anything has changed from their usual habits, have their activities of daily living changed, has their work performance changed? That can give you an indication. One of my patients [said he] was demoted from [his] position, that the demotion was related to cognitive impairment and the way that he was working. That gives you an idea as to where you can help intervene and perhaps make an improvement for that patient’s quality of life, or consider switching treatments,” said Dr. Hernandez.

Men are less likely to report symptoms such as tingling, physical complaints, cognitive difficulties, mood changes, and sexual dysfunction. That doesn’t mean they’re not experiencing issues, though, especially when it comes to sexual problems. Dr. Hernandez recalled one patient who just stared out the window when asked about his sex life. “Then I said, the next time I want your wife to be here, and then she spilled the beans on everything. So it’s important sometimes to include other members of the family or their partners in the conversation to give you some insight. And perhaps that day it wasn’t a priority for him, but then the next time it was a priority for his wife,” he said.

He pointed out that erectile dysfunction could be due to a physiological response to MS, or to psychological effects.

Low testosterone levels may also play a role in MS, since it is a natural anti-inflammatory hormone. Hypogonadism has been found to be high among men with MS in some studies. MS in men is associated with more enhancing lesions, greater cognitive decline, and increased risk of disability, while high levels of testosterone are linked to neuroprotective effects and lower risk of developing MS.

Men with MS are more likely than women to report suicidal thoughts when depressed, and mental health can be taboo, as men may try to solve problems on their own before seeking help. “But a lot of the times they can use a little bit of help, whether it be from talk therapy or meds. With the expansion of telemedicine, virtual care has skyrocketed in psychiatry. I advocate strongly for it. Psychologytoday.com is a very common portal that I recommend so they can look up providers with their insurances, and they can see who gives in person versus virtual care. They can do it from the comfort of their car. I’ve had people in their car crying because they don’t want to be in their house when they talk to me,” said Dr. Hernandez.

Physical struggles can lead men to feel they’ve lost their independence, and that they are no longer the protector of the household. Divorce is common, which can lead to social isolation. One patient wanted to see Dr. Hernandez monthly, a request that he had to decline. “Sometimes they want to discuss these things and they just don’t have someone to talk to,” said Dr. Hernandez. Social support programs through the National MS Society, the MS Foundation, or the Multiple Sclerosis Association of America may sponsor local programs that could be beneficial.

Dr. Hernandez has no relevant financial disclosures.

NASHVILLE, TENNESSEE — Fatigue and sleep problems are common among patients with multiple sclerosis (MS), but there are ways to help them manage these difficulties through personalized care.

Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.

It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
 

Fatigue

When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.

“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.

It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.

A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.

Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.

The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
 

Sleep

Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.

One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.

Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.

As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.

Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.

Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.

Dr. Tworek did not report any disclosures or conflicts of interest.

NASHVILLE, TENNESSEE — Fatigue and sleep problems are common among patients with multiple sclerosis (MS), but there are ways to help them manage these difficulties through personalized care.

Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.

It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
 

Fatigue

When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.

“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.

It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.

A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.

Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.

The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
 

Sleep

Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.

One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.

Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.

As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.

Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.

Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.

Dr. Tworek did not report any disclosures or conflicts of interest.

NASHVILLE, TENNESSEE — Fatigue and sleep problems are common among patients with multiple sclerosis (MS), but there are ways to help them manage these difficulties through personalized care.

Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.

It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
 

Fatigue

When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.

“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.

It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.

A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.

Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.

The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
 

Sleep

Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.

One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.

Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.

As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.

Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.

Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.

Dr. Tworek did not report any disclosures or conflicts of interest.

NASHVILLE, TENNESSEE — Among people with MS who have mild symptoms, non-motor symptoms like dizziness, fatigue, and spasticity predict later perception of balance, walking, and physical quality of life. However, these associations fall away among patients with more severe disease, according to a new study performed in Australia. The findings could eventually help tailor physical activity interventions.

The research grew out of frustrations with developing interventions focused on strength. “There are many systematic reviews showing stronger and stronger evidence that exercise is beneficial. It does change your walking. It does improve your balance,” said Katrina Williams, PhD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.

However, when her group’s intervention studies yielded no statistically significant improvements, she began to search for explanations, and began to suspect heterogeneity among MS patients. Their clinic took all comers, regardless of disability level. “[Our attitude was] we will make it work. We’ll get you actively moving and exercising. But when you break down a lot of those systematic reviews, there’s not a lot of teasing out of disability levels. So, potentially, it is the disability level that might be leading to why some people don’t change or why we’re not getting the statistically significant benefits, because we’re not addressing the individual at their level of disease progression,” said Dr. Williams, who is a senior lecturer in physiotherapy at the University of Queensland, Brisbane, Australia.

“Physiotherapists, we love exercise, we love movement, but we’re a bit unidimensional. It’s some strength training, [or] let’s get on that bike and do cardiovascular. But that may not be enough for individuals who have different symptoms profiles. We’re assuming that the motor profile is the most important, and the one that needs to be addressed in these individuals,” said Dr. Williams.
 

Focusing on Non-Motor Symptoms

When she searched the literature, she could find little evidence of non-motor symptoms correlating to walking, balance, or even quality of life. To dig deeper, her group studied 220 MS patients in Australia who self-reported symptoms of dizziness, vision problems, fatigue, and spasticity. The population had a mean age of 42 years, and 82% were female. They ranged in disease severity from disease step (DS) 0 to DS 6. The researchers categorized respondents as between DS 0 (mild symptoms that were mostly sensory) to DS 3 (MS interferes with walking) and from DS 4 (early cane use) to DS 6 (requiring bilateral walking support).

Deficits were more commonly reported in the DS 4-6 group than the DS 0-3 group with respect to light touch (88% vs 72%), proprioception (63% vs 41%), fatigue (100% vs 96%), and spasticity (78% vs 69%). There were no significant differences in dizziness, vision, or memory/cognition/emotion.

A linear regression model incorporating sensory worsening, age, social participation, perceived deficit, and spasticity showed an R² adjusted value of 0.73. However, when they looked only at DS 0-3 patients, the R² value strengthened to 0.86. Among the DS 4-6 group, the correlation largely disappeared with an R² value of 0.16. Specifically, there were stronger associations in the DS 0-3 group than the overall group (DS 0-6) between perceived walking deficit and sensory worsening (R² 0.45 vs 0.31), fatigue (0.67 vs 0.05), spasticity (0.47 vs 0.16), and balance (0.8 vs 0.16).

“Most non-motor symptoms do have moderate to weak correlations to walking confidence and walking balance, and quality of life, and the correlations do decline as disability worsens. Those with less disability had more correlations that were stronger, particularly for the walking and balance confidence. So [among those] walking without an aid, there are more non-motor correlations aligned to the actual outcomes. In more disabled, they fell away, so there’s something else going on that we do have to look at,” said Dr. Williams.

She called for other clinicians to explore non-motor symptoms in patients with less disability, and the relationships of those symptoms to gait, balance, and overall MS impact, in the hopes that such observations could improve the tailoring of physiotherapy programs.
 

Perception May Differ From Actual Function

During the Q&A session, Nora Fritz, PhD, an associate professor of neurology at Wayne State University, Detroit, Michigan, asked about the lack of correlations seen in more disabled patients. “It’s not exactly what you would expect to happen,” said Dr. Fritz, in an interview.

She asked Dr. Williams if the study had sufficient power to detect associations in patients with more severe disability, since the study had a relatively small sample size and many predictors in its regression model. Dr. Fritz also noted that perceptions may differ from actual function, so actual function can’t be captured using a survey. Dr. Williams responded that the group is now working to incorporate more clinical measures to their correlations.

Another audience member said she was “perplexed” by the drop-off of correlation in the most severe group. She suggested the possibility that as patients become more disabled, they may be less likely to perceive the relatively less severe non-motor symptoms and therefore did not report them.

Dr. Williams and Dr. Fritz have no relevant financial disclosures.

NASHVILLE, TENNESSEE — Among people with MS who have mild symptoms, non-motor symptoms like dizziness, fatigue, and spasticity predict later perception of balance, walking, and physical quality of life. However, these associations fall away among patients with more severe disease, according to a new study performed in Australia. The findings could eventually help tailor physical activity interventions.

The research grew out of frustrations with developing interventions focused on strength. “There are many systematic reviews showing stronger and stronger evidence that exercise is beneficial. It does change your walking. It does improve your balance,” said Katrina Williams, PhD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.

However, when her group’s intervention studies yielded no statistically significant improvements, she began to search for explanations, and began to suspect heterogeneity among MS patients. Their clinic took all comers, regardless of disability level. “[Our attitude was] we will make it work. We’ll get you actively moving and exercising. But when you break down a lot of those systematic reviews, there’s not a lot of teasing out of disability levels. So, potentially, it is the disability level that might be leading to why some people don’t change or why we’re not getting the statistically significant benefits, because we’re not addressing the individual at their level of disease progression,” said Dr. Williams, who is a senior lecturer in physiotherapy at the University of Queensland, Brisbane, Australia.

“Physiotherapists, we love exercise, we love movement, but we’re a bit unidimensional. It’s some strength training, [or] let’s get on that bike and do cardiovascular. But that may not be enough for individuals who have different symptoms profiles. We’re assuming that the motor profile is the most important, and the one that needs to be addressed in these individuals,” said Dr. Williams.
 

Focusing on Non-Motor Symptoms

When she searched the literature, she could find little evidence of non-motor symptoms correlating to walking, balance, or even quality of life. To dig deeper, her group studied 220 MS patients in Australia who self-reported symptoms of dizziness, vision problems, fatigue, and spasticity. The population had a mean age of 42 years, and 82% were female. They ranged in disease severity from disease step (DS) 0 to DS 6. The researchers categorized respondents as between DS 0 (mild symptoms that were mostly sensory) to DS 3 (MS interferes with walking) and from DS 4 (early cane use) to DS 6 (requiring bilateral walking support).

Deficits were more commonly reported in the DS 4-6 group than the DS 0-3 group with respect to light touch (88% vs 72%), proprioception (63% vs 41%), fatigue (100% vs 96%), and spasticity (78% vs 69%). There were no significant differences in dizziness, vision, or memory/cognition/emotion.

A linear regression model incorporating sensory worsening, age, social participation, perceived deficit, and spasticity showed an R² adjusted value of 0.73. However, when they looked only at DS 0-3 patients, the R² value strengthened to 0.86. Among the DS 4-6 group, the correlation largely disappeared with an R² value of 0.16. Specifically, there were stronger associations in the DS 0-3 group than the overall group (DS 0-6) between perceived walking deficit and sensory worsening (R² 0.45 vs 0.31), fatigue (0.67 vs 0.05), spasticity (0.47 vs 0.16), and balance (0.8 vs 0.16).

“Most non-motor symptoms do have moderate to weak correlations to walking confidence and walking balance, and quality of life, and the correlations do decline as disability worsens. Those with less disability had more correlations that were stronger, particularly for the walking and balance confidence. So [among those] walking without an aid, there are more non-motor correlations aligned to the actual outcomes. In more disabled, they fell away, so there’s something else going on that we do have to look at,” said Dr. Williams.

She called for other clinicians to explore non-motor symptoms in patients with less disability, and the relationships of those symptoms to gait, balance, and overall MS impact, in the hopes that such observations could improve the tailoring of physiotherapy programs.
 

Perception May Differ From Actual Function

During the Q&A session, Nora Fritz, PhD, an associate professor of neurology at Wayne State University, Detroit, Michigan, asked about the lack of correlations seen in more disabled patients. “It’s not exactly what you would expect to happen,” said Dr. Fritz, in an interview.

She asked Dr. Williams if the study had sufficient power to detect associations in patients with more severe disability, since the study had a relatively small sample size and many predictors in its regression model. Dr. Fritz also noted that perceptions may differ from actual function, so actual function can’t be captured using a survey. Dr. Williams responded that the group is now working to incorporate more clinical measures to their correlations.

Another audience member said she was “perplexed” by the drop-off of correlation in the most severe group. She suggested the possibility that as patients become more disabled, they may be less likely to perceive the relatively less severe non-motor symptoms and therefore did not report them.

Dr. Williams and Dr. Fritz have no relevant financial disclosures.

NASHVILLE, TENNESSEE — Among people with MS who have mild symptoms, non-motor symptoms like dizziness, fatigue, and spasticity predict later perception of balance, walking, and physical quality of life. However, these associations fall away among patients with more severe disease, according to a new study performed in Australia. The findings could eventually help tailor physical activity interventions.

The research grew out of frustrations with developing interventions focused on strength. “There are many systematic reviews showing stronger and stronger evidence that exercise is beneficial. It does change your walking. It does improve your balance,” said Katrina Williams, PhD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.

However, when her group’s intervention studies yielded no statistically significant improvements, she began to search for explanations, and began to suspect heterogeneity among MS patients. Their clinic took all comers, regardless of disability level. “[Our attitude was] we will make it work. We’ll get you actively moving and exercising. But when you break down a lot of those systematic reviews, there’s not a lot of teasing out of disability levels. So, potentially, it is the disability level that might be leading to why some people don’t change or why we’re not getting the statistically significant benefits, because we’re not addressing the individual at their level of disease progression,” said Dr. Williams, who is a senior lecturer in physiotherapy at the University of Queensland, Brisbane, Australia.

“Physiotherapists, we love exercise, we love movement, but we’re a bit unidimensional. It’s some strength training, [or] let’s get on that bike and do cardiovascular. But that may not be enough for individuals who have different symptoms profiles. We’re assuming that the motor profile is the most important, and the one that needs to be addressed in these individuals,” said Dr. Williams.
 

Focusing on Non-Motor Symptoms

When she searched the literature, she could find little evidence of non-motor symptoms correlating to walking, balance, or even quality of life. To dig deeper, her group studied 220 MS patients in Australia who self-reported symptoms of dizziness, vision problems, fatigue, and spasticity. The population had a mean age of 42 years, and 82% were female. They ranged in disease severity from disease step (DS) 0 to DS 6. The researchers categorized respondents as between DS 0 (mild symptoms that were mostly sensory) to DS 3 (MS interferes with walking) and from DS 4 (early cane use) to DS 6 (requiring bilateral walking support).

Deficits were more commonly reported in the DS 4-6 group than the DS 0-3 group with respect to light touch (88% vs 72%), proprioception (63% vs 41%), fatigue (100% vs 96%), and spasticity (78% vs 69%). There were no significant differences in dizziness, vision, or memory/cognition/emotion.

A linear regression model incorporating sensory worsening, age, social participation, perceived deficit, and spasticity showed an R² adjusted value of 0.73. However, when they looked only at DS 0-3 patients, the R² value strengthened to 0.86. Among the DS 4-6 group, the correlation largely disappeared with an R² value of 0.16. Specifically, there were stronger associations in the DS 0-3 group than the overall group (DS 0-6) between perceived walking deficit and sensory worsening (R² 0.45 vs 0.31), fatigue (0.67 vs 0.05), spasticity (0.47 vs 0.16), and balance (0.8 vs 0.16).

“Most non-motor symptoms do have moderate to weak correlations to walking confidence and walking balance, and quality of life, and the correlations do decline as disability worsens. Those with less disability had more correlations that were stronger, particularly for the walking and balance confidence. So [among those] walking without an aid, there are more non-motor correlations aligned to the actual outcomes. In more disabled, they fell away, so there’s something else going on that we do have to look at,” said Dr. Williams.

She called for other clinicians to explore non-motor symptoms in patients with less disability, and the relationships of those symptoms to gait, balance, and overall MS impact, in the hopes that such observations could improve the tailoring of physiotherapy programs.
 

Perception May Differ From Actual Function

During the Q&A session, Nora Fritz, PhD, an associate professor of neurology at Wayne State University, Detroit, Michigan, asked about the lack of correlations seen in more disabled patients. “It’s not exactly what you would expect to happen,” said Dr. Fritz, in an interview.

She asked Dr. Williams if the study had sufficient power to detect associations in patients with more severe disability, since the study had a relatively small sample size and many predictors in its regression model. Dr. Fritz also noted that perceptions may differ from actual function, so actual function can’t be captured using a survey. Dr. Williams responded that the group is now working to incorporate more clinical measures to their correlations.

Another audience member said she was “perplexed” by the drop-off of correlation in the most severe group. She suggested the possibility that as patients become more disabled, they may be less likely to perceive the relatively less severe non-motor symptoms and therefore did not report them.

Dr. Williams and Dr. Fritz have no relevant financial disclosures.

NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.

A new intervention seeks to help patients with MS reduce stress using biofeedback, employing simple, readily available pulse oximeters and focusing on breathing and other simple coping skills.

Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).

Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.

“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.

That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.

The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.

Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.

They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.

In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.

The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.

The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).

In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.

The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.

The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.

During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.

Dr. Sullivan did not report any relevant disclosures.

NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.

A new intervention seeks to help patients with MS reduce stress using biofeedback, employing simple, readily available pulse oximeters and focusing on breathing and other simple coping skills.

Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).

Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.

“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.

That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.

The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.

Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.

They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.

In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.

The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.

The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).

In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.

The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.

The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.

During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.

Dr. Sullivan did not report any relevant disclosures.

NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.

A new intervention seeks to help patients with MS reduce stress using biofeedback, employing simple, readily available pulse oximeters and focusing on breathing and other simple coping skills.

Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).

Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.

“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.

That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.

The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.

Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.

They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.

In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.

The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.

The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).

In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.

The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.

The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.

During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.

Dr. Sullivan did not report any relevant disclosures.

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

CHICAGO — At the 2024 AGA Tech Summit, held April 11-12 at the Chicago headquarters of MATTER, a global healthcare startup incubator, five companies made their pitch to be the winner of the Shark Tank competition that recognizes an outstanding tech start up in the gastroenterology field.

After the companies’ rapid-fire pitches and Q&A sessions, four judges convened to determine a winner and returned to make an announcement.

The winner was Arithmedics, which uses AI technology to automate billing codes. Founder Venthan Elango, PhD, has worked as a software engineer at Google, Urban Engines, and Georgia Tech, and his wife of 17 years is Renumathy Dhanasekaran, MD, PhD, a gastroenterologist and assistant professor of medicine at Stanford (California) University.

Their marriage has brought a unique perspective, according to Dr. Elango. “There isn’t a single day that goes by when she talks to me about the inefficiencies in healthcare, and then I say, ‘this can be easily solved with a software solution,’ ” he said.

Arithmedics

Stanford University

• Aspero Medical: Balloon overtube that maximizes frictional properties to improve mucosal wall traction and anchoring consistency. (Voted ‘fan favorite’ by AGA Tech Summit attendees)
• Aurora Medical Technologies: Minimally invasive, guided, tissue-anchoring suturing system for complex endoscopic procedures.
• Ergami Endoscopy: Flexible overtube capable of automatic insertion and fixation in the colon, which could potentially eliminate sedation and prevent endoscopic injuries to the physician.
• Lazurite: Wireless surgical camera that eliminates the need for light or video cables, avoiding the associated fire, trip, and contamination hazards.

The judges were swayed by Arithmedics’ practical solution to a widespread problem. “There is for sure a need in terms of inaccurate billing and billing codes that are wrong. There’s lost revenue for physicians around that. So I think we were really focused from a judging standpoint on the fact that their solution was filling truly an unmet need,” said judge Andrea Vossler, a managing director of Varia Ventures, which has partnered with AGA to launch and manage the GI Opportunity Fund, an AGA-member venture fund.

“We were really focused on how to assist physicians in terms of supporting their practices, and really changing what you’re doing. I think AI has the ability to do that, so we liked that about the company,” she added.

The company is an example of how AI is poised to alter healthcare, according to Ms. Vossler. “I think it’s massive. I think we’re at the very beginning of its impact on healthcare,” she said.

Another judge had a similar view. “They won because there is a screaming need to fix billing. So, it’s well known that lots of money is indeed lost in billing practices, which are stressful for office personnel and stressful for physicians. They can fulfill a long-standing need, and we thought that that was the success story,” said Christopher Gostout, MD, emeritus professor of medicine at Mayo Clinic in Rochester, Minnesota.

Dr. Gostout offered advice for gastroenterologists and other physicians interested in starting tech companies. It’s imperative to be a realist, he said. “Is there a real market for it, or [is it just] a niche market? Does your device have legs — can it expand and can evolve into other [spin-off] products? These are things you need to think about because one-offs or single-trick ponies are pretty hard to move along now,” said Dr. Gostout.

He recommended that entrepreneurs apply for Small Business Innovation Research (SBIR) grants. “I think it’s a great opportunity to bring in money and get the ball rolling.”

Finally, he advised entrepreneurs to be thoughtful about their advisory groups. Founders may be tempted to find the highest profile names they can to give the business gravitas, but those big names may not have the best knowledge base to understand the problems that the technology is meant to address. “I’ve seen businesses fail because they went for marquee names that really were not helpful, and they didn’t do their due diligence in seeking out really useful value. You don’t need a lot of advisers, just a couple of really good ones,” said Dr. Gostout.

The summit was sponsored by the AGA Center for GI Innovation and Technology.

Dr. Gostout has founded and advises AdaptivEndo and Lean Medical. He is a consultant to Boston Scientific. Dr. Dhanasekaran has no financial disclosures. Ms. Vossler is an employee of Varia Ventures, which is an investment partner to AGA. Dr. Elango is an employee of Arithmedics.

CHICAGO — At the 2024 AGA Tech Summit, held April 11-12 at the Chicago headquarters of MATTER, a global healthcare startup incubator, five companies made their pitch to be the winner of the Shark Tank competition that recognizes an outstanding tech start up in the gastroenterology field.

After the companies’ rapid-fire pitches and Q&A sessions, four judges convened to determine a winner and returned to make an announcement.

The winner was Arithmedics, which uses AI technology to automate billing codes. Founder Venthan Elango, PhD, has worked as a software engineer at Google, Urban Engines, and Georgia Tech, and his wife of 17 years is Renumathy Dhanasekaran, MD, PhD, a gastroenterologist and assistant professor of medicine at Stanford (California) University.

Their marriage has brought a unique perspective, according to Dr. Elango. “There isn’t a single day that goes by when she talks to me about the inefficiencies in healthcare, and then I say, ‘this can be easily solved with a software solution,’ ” he said.

Arithmedics

Stanford University

• Aspero Medical: Balloon overtube that maximizes frictional properties to improve mucosal wall traction and anchoring consistency. (Voted ‘fan favorite’ by AGA Tech Summit attendees)
• Aurora Medical Technologies: Minimally invasive, guided, tissue-anchoring suturing system for complex endoscopic procedures.
• Ergami Endoscopy: Flexible overtube capable of automatic insertion and fixation in the colon, which could potentially eliminate sedation and prevent endoscopic injuries to the physician.
• Lazurite: Wireless surgical camera that eliminates the need for light or video cables, avoiding the associated fire, trip, and contamination hazards.

The judges were swayed by Arithmedics’ practical solution to a widespread problem. “There is for sure a need in terms of inaccurate billing and billing codes that are wrong. There’s lost revenue for physicians around that. So I think we were really focused from a judging standpoint on the fact that their solution was filling truly an unmet need,” said judge Andrea Vossler, a managing director of Varia Ventures, which has partnered with AGA to launch and manage the GI Opportunity Fund, an AGA-member venture fund.

“We were really focused on how to assist physicians in terms of supporting their practices, and really changing what you’re doing. I think AI has the ability to do that, so we liked that about the company,” she added.

The company is an example of how AI is poised to alter healthcare, according to Ms. Vossler. “I think it’s massive. I think we’re at the very beginning of its impact on healthcare,” she said.

Another judge had a similar view. “They won because there is a screaming need to fix billing. So, it’s well known that lots of money is indeed lost in billing practices, which are stressful for office personnel and stressful for physicians. They can fulfill a long-standing need, and we thought that that was the success story,” said Christopher Gostout, MD, emeritus professor of medicine at Mayo Clinic in Rochester, Minnesota.

Dr. Gostout offered advice for gastroenterologists and other physicians interested in starting tech companies. It’s imperative to be a realist, he said. “Is there a real market for it, or [is it just] a niche market? Does your device have legs — can it expand and can evolve into other [spin-off] products? These are things you need to think about because one-offs or single-trick ponies are pretty hard to move along now,” said Dr. Gostout.

He recommended that entrepreneurs apply for Small Business Innovation Research (SBIR) grants. “I think it’s a great opportunity to bring in money and get the ball rolling.”

Finally, he advised entrepreneurs to be thoughtful about their advisory groups. Founders may be tempted to find the highest profile names they can to give the business gravitas, but those big names may not have the best knowledge base to understand the problems that the technology is meant to address. “I’ve seen businesses fail because they went for marquee names that really were not helpful, and they didn’t do their due diligence in seeking out really useful value. You don’t need a lot of advisers, just a couple of really good ones,” said Dr. Gostout.

The summit was sponsored by the AGA Center for GI Innovation and Technology.

Dr. Gostout has founded and advises AdaptivEndo and Lean Medical. He is a consultant to Boston Scientific. Dr. Dhanasekaran has no financial disclosures. Ms. Vossler is an employee of Varia Ventures, which is an investment partner to AGA. Dr. Elango is an employee of Arithmedics.

CHICAGO — At the 2024 AGA Tech Summit, held April 11-12 at the Chicago headquarters of MATTER, a global healthcare startup incubator, five companies made their pitch to be the winner of the Shark Tank competition that recognizes an outstanding tech start up in the gastroenterology field.

After the companies’ rapid-fire pitches and Q&A sessions, four judges convened to determine a winner and returned to make an announcement.

The winner was Arithmedics, which uses AI technology to automate billing codes. Founder Venthan Elango, PhD, has worked as a software engineer at Google, Urban Engines, and Georgia Tech, and his wife of 17 years is Renumathy Dhanasekaran, MD, PhD, a gastroenterologist and assistant professor of medicine at Stanford (California) University.

Their marriage has brought a unique perspective, according to Dr. Elango. “There isn’t a single day that goes by when she talks to me about the inefficiencies in healthcare, and then I say, ‘this can be easily solved with a software solution,’ ” he said.

Arithmedics

Stanford University

• Aspero Medical: Balloon overtube that maximizes frictional properties to improve mucosal wall traction and anchoring consistency. (Voted ‘fan favorite’ by AGA Tech Summit attendees)
• Aurora Medical Technologies: Minimally invasive, guided, tissue-anchoring suturing system for complex endoscopic procedures.
• Ergami Endoscopy: Flexible overtube capable of automatic insertion and fixation in the colon, which could potentially eliminate sedation and prevent endoscopic injuries to the physician.
• Lazurite: Wireless surgical camera that eliminates the need for light or video cables, avoiding the associated fire, trip, and contamination hazards.

The judges were swayed by Arithmedics’ practical solution to a widespread problem. “There is for sure a need in terms of inaccurate billing and billing codes that are wrong. There’s lost revenue for physicians around that. So I think we were really focused from a judging standpoint on the fact that their solution was filling truly an unmet need,” said judge Andrea Vossler, a managing director of Varia Ventures, which has partnered with AGA to launch and manage the GI Opportunity Fund, an AGA-member venture fund.

“We were really focused on how to assist physicians in terms of supporting their practices, and really changing what you’re doing. I think AI has the ability to do that, so we liked that about the company,” she added.

The company is an example of how AI is poised to alter healthcare, according to Ms. Vossler. “I think it’s massive. I think we’re at the very beginning of its impact on healthcare,” she said.

Another judge had a similar view. “They won because there is a screaming need to fix billing. So, it’s well known that lots of money is indeed lost in billing practices, which are stressful for office personnel and stressful for physicians. They can fulfill a long-standing need, and we thought that that was the success story,” said Christopher Gostout, MD, emeritus professor of medicine at Mayo Clinic in Rochester, Minnesota.

Dr. Gostout offered advice for gastroenterologists and other physicians interested in starting tech companies. It’s imperative to be a realist, he said. “Is there a real market for it, or [is it just] a niche market? Does your device have legs — can it expand and can evolve into other [spin-off] products? These are things you need to think about because one-offs or single-trick ponies are pretty hard to move along now,” said Dr. Gostout.

He recommended that entrepreneurs apply for Small Business Innovation Research (SBIR) grants. “I think it’s a great opportunity to bring in money and get the ball rolling.”

Finally, he advised entrepreneurs to be thoughtful about their advisory groups. Founders may be tempted to find the highest profile names they can to give the business gravitas, but those big names may not have the best knowledge base to understand the problems that the technology is meant to address. “I’ve seen businesses fail because they went for marquee names that really were not helpful, and they didn’t do their due diligence in seeking out really useful value. You don’t need a lot of advisers, just a couple of really good ones,” said Dr. Gostout.

The summit was sponsored by the AGA Center for GI Innovation and Technology.

Dr. Gostout has founded and advises AdaptivEndo and Lean Medical. He is a consultant to Boston Scientific. Dr. Dhanasekaran has no financial disclosures. Ms. Vossler is an employee of Varia Ventures, which is an investment partner to AGA. Dr. Elango is an employee of Arithmedics.

DENVER — A retrospective analysis of pediatric patients with Lennox-Gastaut syndrome (LGS) suggests that the antiseizure medication cenobamate (SK Life Sciences) in combination with existing lines of therapy may be associated with fewer hospital in-patient days and emergency room visits. The conclusions were reached by comparing outcomes to patient historical data, though they were not analyzed statistically.

A Proof-of-Concept Study

In an interview, Karen Keough, MD, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology, conceded the key limitation was that the researchers were not able to perform statistical analysis due to the nature of the data. “It’s just showing trends. It’s proof of concept that cenobamate can be effective in one of the most refractory forms of epilepsy, which always includes focal seizures. That’s what led to the initial FDA indication, but we also know that this medication has a lot of promise and is probably going to be effective in other forms of epilepsy and probably in other seizure types,” said Dr. Keough, who is a neurologist at Pediatrix Child Neurology Consultants of Austin, Texas.

Although she has seen significant improvements in many patients, Dr. Keough reported that most patients become refractory again. “Unfortunately, honeymoons are probably real in cenobamate. Continuing to follow those patients as I do, since they’re my own patients, I have quite a few who had more than a year of seizure freedom, [but] their seizures are back, though not as bad as they were before cenobamate. I just can’t get them back to that 100% control category. I do have a few that are still in the 100% control category, but not very many,” she said.

She also presented a retrospective chart review of 36 LGS patients between the ages of 1 and 27 years at the American Epilepsy Society in December 2023, which showed that addition of cenobamate was associated with a reduction in seizure frequency in 85% of patients. “It was a profound number of patients who had long periods of seizure freedom,” she said.
 

A Promising Treatment Option

Dr. Keough is considering moving cenobamate up in the treatment sequence of new LGS patients. “I don’t use cenobamate first line in anyone because we have good first-line agents for simple epilepsy in Lennox-Gastaut, but I’m bringing out cenobamate pretty early in the course, because I do think it has superior efficacy compared with most other drugs that we have available. Most of my patients are very established and they’ve seen lots of other drugs. For many patients, there are only a couple of drugs left on the list that [they] have never tried, but we’re going to put cenobamate at the top of that. For my newer diagnoses, I’m going to bring it out much earlier,” she said, though other drugs such as clobazam (Onfi) would still rank ahead of cenobamate.

The study was drawn from records of the HealthVerity Marketplace Database, which includes more than 150 commercial, Medicare, and Medicaid payers. It included 76 patients aged 17 or under who took at least one antiseizure medication between May 2020 and December 2022, and who had filled at least two prescriptions of cenobamate and had 180 or more days of medical and pharmacy enrollment. The mean age was 13.4 years (5.3% 0-5 years, 15.8% 6-11 years, 78.9% 12-17 years), and 40.8% were female. Seizure types included absence (17.1%), focal (75.0%), and generalized tonic-clonic (86.8%). All patients had a history of intractable seizures, 80.3% had a history of status epilepticus, and 28.9% had a history of infantile seizures. A little more than one fourth (27.6%) of patients had commercial insurance. In the previous 90 days, 21.1% had had an emergency room visit or in-patient hospital stay.

Common antiseizure medications taken with cenobamate included cannabidiol (n = 14), clobazam (n = 8), and levetiracetam (n = 18).

During the cenobamate treatment period, patients had a lower incidence of epilepsy-related inpatient days per year (3.36 vs 3.94), epilepsy-related ER visits per year (0.66 vs 1.19), and likelihood of requiring a new line of epilepsy therapy (35.5% vs 100%).
 

‘Promising’ Results, but More Research Is Needed

The fact that cenobamate was used in combination with other therapies, plus the lack of a control group, makes it difficult to determine if cenobamate was actually responsible for the improvements, according to Nassim Zecavati, MD, who was asked for comment on the study. “I think the results are promising, but there’s obviously a need for a randomized, controlled trial to understand whether it was this medication or the combination of cenobamate with [other medications]. How do we know that this isn’t a compound effect, that it’s multifactorial, and a combination of multiple medications versus the cenobamate?” she said.

Still, she noted that LGS patients are highly vulnerable to hospital admissions and status epilepticus, making the parameters examined in the study valid and important. “I think that this drug likely has a role in the treatment of patients with LGS, particularly pediatric patients. I think we just need more data,” said Dr. Zecavati, who is director of Epilepsy at the Children’s Hospital of Richmond in Virginia and associate professor of Neurology at Virginia Commonwealth University.

Dr. Keough is a speaker for SK Life Sciences. Dr. Zecavati has no relevant financial disclosures.

DENVER — A retrospective analysis of pediatric patients with Lennox-Gastaut syndrome (LGS) suggests that the antiseizure medication cenobamate (SK Life Sciences) in combination with existing lines of therapy may be associated with fewer hospital in-patient days and emergency room visits. The conclusions were reached by comparing outcomes to patient historical data, though they were not analyzed statistically.

A Proof-of-Concept Study

In an interview, Karen Keough, MD, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology, conceded the key limitation was that the researchers were not able to perform statistical analysis due to the nature of the data. “It’s just showing trends. It’s proof of concept that cenobamate can be effective in one of the most refractory forms of epilepsy, which always includes focal seizures. That’s what led to the initial FDA indication, but we also know that this medication has a lot of promise and is probably going to be effective in other forms of epilepsy and probably in other seizure types,” said Dr. Keough, who is a neurologist at Pediatrix Child Neurology Consultants of Austin, Texas.

Although she has seen significant improvements in many patients, Dr. Keough reported that most patients become refractory again. “Unfortunately, honeymoons are probably real in cenobamate. Continuing to follow those patients as I do, since they’re my own patients, I have quite a few who had more than a year of seizure freedom, [but] their seizures are back, though not as bad as they were before cenobamate. I just can’t get them back to that 100% control category. I do have a few that are still in the 100% control category, but not very many,” she said.

She also presented a retrospective chart review of 36 LGS patients between the ages of 1 and 27 years at the American Epilepsy Society in December 2023, which showed that addition of cenobamate was associated with a reduction in seizure frequency in 85% of patients. “It was a profound number of patients who had long periods of seizure freedom,” she said.
 

A Promising Treatment Option

Dr. Keough is considering moving cenobamate up in the treatment sequence of new LGS patients. “I don’t use cenobamate first line in anyone because we have good first-line agents for simple epilepsy in Lennox-Gastaut, but I’m bringing out cenobamate pretty early in the course, because I do think it has superior efficacy compared with most other drugs that we have available. Most of my patients are very established and they’ve seen lots of other drugs. For many patients, there are only a couple of drugs left on the list that [they] have never tried, but we’re going to put cenobamate at the top of that. For my newer diagnoses, I’m going to bring it out much earlier,” she said, though other drugs such as clobazam (Onfi) would still rank ahead of cenobamate.

The study was drawn from records of the HealthVerity Marketplace Database, which includes more than 150 commercial, Medicare, and Medicaid payers. It included 76 patients aged 17 or under who took at least one antiseizure medication between May 2020 and December 2022, and who had filled at least two prescriptions of cenobamate and had 180 or more days of medical and pharmacy enrollment. The mean age was 13.4 years (5.3% 0-5 years, 15.8% 6-11 years, 78.9% 12-17 years), and 40.8% were female. Seizure types included absence (17.1%), focal (75.0%), and generalized tonic-clonic (86.8%). All patients had a history of intractable seizures, 80.3% had a history of status epilepticus, and 28.9% had a history of infantile seizures. A little more than one fourth (27.6%) of patients had commercial insurance. In the previous 90 days, 21.1% had had an emergency room visit or in-patient hospital stay.

Common antiseizure medications taken with cenobamate included cannabidiol (n = 14), clobazam (n = 8), and levetiracetam (n = 18).

During the cenobamate treatment period, patients had a lower incidence of epilepsy-related inpatient days per year (3.36 vs 3.94), epilepsy-related ER visits per year (0.66 vs 1.19), and likelihood of requiring a new line of epilepsy therapy (35.5% vs 100%).
 

‘Promising’ Results, but More Research Is Needed

The fact that cenobamate was used in combination with other therapies, plus the lack of a control group, makes it difficult to determine if cenobamate was actually responsible for the improvements, according to Nassim Zecavati, MD, who was asked for comment on the study. “I think the results are promising, but there’s obviously a need for a randomized, controlled trial to understand whether it was this medication or the combination of cenobamate with [other medications]. How do we know that this isn’t a compound effect, that it’s multifactorial, and a combination of multiple medications versus the cenobamate?” she said.

Still, she noted that LGS patients are highly vulnerable to hospital admissions and status epilepticus, making the parameters examined in the study valid and important. “I think that this drug likely has a role in the treatment of patients with LGS, particularly pediatric patients. I think we just need more data,” said Dr. Zecavati, who is director of Epilepsy at the Children’s Hospital of Richmond in Virginia and associate professor of Neurology at Virginia Commonwealth University.

Dr. Keough is a speaker for SK Life Sciences. Dr. Zecavati has no relevant financial disclosures.

DENVER — A retrospective analysis of pediatric patients with Lennox-Gastaut syndrome (LGS) suggests that the antiseizure medication cenobamate (SK Life Sciences) in combination with existing lines of therapy may be associated with fewer hospital in-patient days and emergency room visits. The conclusions were reached by comparing outcomes to patient historical data, though they were not analyzed statistically.

A Proof-of-Concept Study

In an interview, Karen Keough, MD, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology, conceded the key limitation was that the researchers were not able to perform statistical analysis due to the nature of the data. “It’s just showing trends. It’s proof of concept that cenobamate can be effective in one of the most refractory forms of epilepsy, which always includes focal seizures. That’s what led to the initial FDA indication, but we also know that this medication has a lot of promise and is probably going to be effective in other forms of epilepsy and probably in other seizure types,” said Dr. Keough, who is a neurologist at Pediatrix Child Neurology Consultants of Austin, Texas.

Although she has seen significant improvements in many patients, Dr. Keough reported that most patients become refractory again. “Unfortunately, honeymoons are probably real in cenobamate. Continuing to follow those patients as I do, since they’re my own patients, I have quite a few who had more than a year of seizure freedom, [but] their seizures are back, though not as bad as they were before cenobamate. I just can’t get them back to that 100% control category. I do have a few that are still in the 100% control category, but not very many,” she said.

She also presented a retrospective chart review of 36 LGS patients between the ages of 1 and 27 years at the American Epilepsy Society in December 2023, which showed that addition of cenobamate was associated with a reduction in seizure frequency in 85% of patients. “It was a profound number of patients who had long periods of seizure freedom,” she said.
 

A Promising Treatment Option

Dr. Keough is considering moving cenobamate up in the treatment sequence of new LGS patients. “I don’t use cenobamate first line in anyone because we have good first-line agents for simple epilepsy in Lennox-Gastaut, but I’m bringing out cenobamate pretty early in the course, because I do think it has superior efficacy compared with most other drugs that we have available. Most of my patients are very established and they’ve seen lots of other drugs. For many patients, there are only a couple of drugs left on the list that [they] have never tried, but we’re going to put cenobamate at the top of that. For my newer diagnoses, I’m going to bring it out much earlier,” she said, though other drugs such as clobazam (Onfi) would still rank ahead of cenobamate.

The study was drawn from records of the HealthVerity Marketplace Database, which includes more than 150 commercial, Medicare, and Medicaid payers. It included 76 patients aged 17 or under who took at least one antiseizure medication between May 2020 and December 2022, and who had filled at least two prescriptions of cenobamate and had 180 or more days of medical and pharmacy enrollment. The mean age was 13.4 years (5.3% 0-5 years, 15.8% 6-11 years, 78.9% 12-17 years), and 40.8% were female. Seizure types included absence (17.1%), focal (75.0%), and generalized tonic-clonic (86.8%). All patients had a history of intractable seizures, 80.3% had a history of status epilepticus, and 28.9% had a history of infantile seizures. A little more than one fourth (27.6%) of patients had commercial insurance. In the previous 90 days, 21.1% had had an emergency room visit or in-patient hospital stay.

Common antiseizure medications taken with cenobamate included cannabidiol (n = 14), clobazam (n = 8), and levetiracetam (n = 18).

During the cenobamate treatment period, patients had a lower incidence of epilepsy-related inpatient days per year (3.36 vs 3.94), epilepsy-related ER visits per year (0.66 vs 1.19), and likelihood of requiring a new line of epilepsy therapy (35.5% vs 100%).
 

‘Promising’ Results, but More Research Is Needed

The fact that cenobamate was used in combination with other therapies, plus the lack of a control group, makes it difficult to determine if cenobamate was actually responsible for the improvements, according to Nassim Zecavati, MD, who was asked for comment on the study. “I think the results are promising, but there’s obviously a need for a randomized, controlled trial to understand whether it was this medication or the combination of cenobamate with [other medications]. How do we know that this isn’t a compound effect, that it’s multifactorial, and a combination of multiple medications versus the cenobamate?” she said.

Still, she noted that LGS patients are highly vulnerable to hospital admissions and status epilepticus, making the parameters examined in the study valid and important. “I think that this drug likely has a role in the treatment of patients with LGS, particularly pediatric patients. I think we just need more data,” said Dr. Zecavati, who is director of Epilepsy at the Children’s Hospital of Richmond in Virginia and associate professor of Neurology at Virginia Commonwealth University.

Dr. Keough is a speaker for SK Life Sciences. Dr. Zecavati has no relevant financial disclosures.

DENVER — Among patients with major depressive disorder, transcranial magnetic stimulation (TMS) had similar efficacy to electroconvulsive therapy (ECT), according to results from a retrospective study of patients treated in the past 20 years.

“We always learn in our textbooks that after about two or three medication trials is when you can start exploring more serious treatment protocols, such as ECT or TMS, but a lot of these patients weren’t going forward with it, and I was curious about it. I figured that TMS, which is a less expensive, less scary procedure that patients would more likely be open to, that is also approved for treatment resistant depression, would be a good alternative to ECT,” said Anuttham Kandhadai, a third-year medical student at University of Texas Medical Branch at Galveston, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
 

Study Findings Lead to More Questions

The researchers found lower rates of depressive episodes, suicidal attempts, and suicidal ideation among patients treated with TMS, but an important limitation was that the researchers did not know the severity of the depression in the two patient groups, according to Branch Coslett, MD, who attended the session and has performed research with TMS to treat aphasia in stroke patients. “I think it’s a very interesting study, and certainly something worth pursuing, but given that ECT is only used as a last resort, whereas TMS is often used as a second-line therapy, I think you’re really talking about very different populations that have had these treatments,” said Dr. Coslett.

Mr. Kandhadai recognized the limitations of the study and looks forward to expanding the research. “I’d love to explore cost effectiveness of the treatments. I’d love to explore patient familiarity and patient comfort with different treatments. And I’d also love to explore a more controlled study that can determine how severe someone’s depression is, and then be able to control for that and explore the outcomes based on the treatment protocol,” he said.

The ideal comparative study would be prospective, “but that will never be done. One Flew Over the Cuckoo’s Nest and similar sources of information have really poisoned the well,” said Dr. Coslett. However, he noted that advances have been made in ECT, and that targeting the right hemisphere produces fewer side effects: “The outcomes from unilateral right hemisphere stimulation are said to be every bit as good or maybe better, and you don’t get the confusion, you don’t get the memory loss, you don’t get all that sort of stuff that you’d expect when somebody has a prolonged, generalized tonic-clonic seizure.”

Still, people are naturally reluctant to undergo ECT. “I’ve seen it. It’s pretty barbaric. It’s better now and at my institution, people do get it, but they really, really have to be intractable,” he said.
 

Comparing Treatment Options

Mr. Kandhadai and his co-authors used the TriNetX database to identify patients with treatment-resistant major depressive disorder who received TMS or ECT in the past 20 years. There were 2,916 patients in both cohorts, who were matched by age, sex, ethnicity, mood and behavioral disorders, endocrine disorders, intellectual disabilities, cerebrovascular disease, and other nervous system disorders. The mean age at treatment was 48.2 years, 38.5% were male, and 3.1% were Black or African American.

Short-term outcomes favored TMS, including the frequency of disorientation (0.41% vs 2.81%), retrograde amnesia (0.34% vs 0.65%), and headache (4.36% vs 7.20%). Long-term outcomes from 1 month to 5 years post treatment were also better in the TMS group, including depressive episodes (44.99% vs 53.77%), suicide attempts (3.98% vs 6.86%), and suicidal ideation (12.38% vs 23.49%). Kaplan-Meier curve analysis between 1 month and 5 years showed a benefit to TMS in probability of not experiencing a depressive episode, and not experiencing suicidal ideation.

“ECT has been the gold standard of treatment resistant depression for a long time, and it deserves to be. I think it’s something you should offer your patients. Not everyone might be comfortable with it, and if they’re not, I think it’s important to not stop the conversation there, but to offer something like TMS because TMS is something that might be more accessible to patients. It might be more affordable, and it might be less scary,” said Mr. Kandhadai

Mr. Kandhadai and Dr. Coslett have no relevant financial disclosures.

DENVER — Among patients with major depressive disorder, transcranial magnetic stimulation (TMS) had similar efficacy to electroconvulsive therapy (ECT), according to results from a retrospective study of patients treated in the past 20 years.

“We always learn in our textbooks that after about two or three medication trials is when you can start exploring more serious treatment protocols, such as ECT or TMS, but a lot of these patients weren’t going forward with it, and I was curious about it. I figured that TMS, which is a less expensive, less scary procedure that patients would more likely be open to, that is also approved for treatment resistant depression, would be a good alternative to ECT,” said Anuttham Kandhadai, a third-year medical student at University of Texas Medical Branch at Galveston, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
 

Study Findings Lead to More Questions

The researchers found lower rates of depressive episodes, suicidal attempts, and suicidal ideation among patients treated with TMS, but an important limitation was that the researchers did not know the severity of the depression in the two patient groups, according to Branch Coslett, MD, who attended the session and has performed research with TMS to treat aphasia in stroke patients. “I think it’s a very interesting study, and certainly something worth pursuing, but given that ECT is only used as a last resort, whereas TMS is often used as a second-line therapy, I think you’re really talking about very different populations that have had these treatments,” said Dr. Coslett.

Mr. Kandhadai recognized the limitations of the study and looks forward to expanding the research. “I’d love to explore cost effectiveness of the treatments. I’d love to explore patient familiarity and patient comfort with different treatments. And I’d also love to explore a more controlled study that can determine how severe someone’s depression is, and then be able to control for that and explore the outcomes based on the treatment protocol,” he said.

The ideal comparative study would be prospective, “but that will never be done. One Flew Over the Cuckoo’s Nest and similar sources of information have really poisoned the well,” said Dr. Coslett. However, he noted that advances have been made in ECT, and that targeting the right hemisphere produces fewer side effects: “The outcomes from unilateral right hemisphere stimulation are said to be every bit as good or maybe better, and you don’t get the confusion, you don’t get the memory loss, you don’t get all that sort of stuff that you’d expect when somebody has a prolonged, generalized tonic-clonic seizure.”

Still, people are naturally reluctant to undergo ECT. “I’ve seen it. It’s pretty barbaric. It’s better now and at my institution, people do get it, but they really, really have to be intractable,” he said.
 

Comparing Treatment Options

Mr. Kandhadai and his co-authors used the TriNetX database to identify patients with treatment-resistant major depressive disorder who received TMS or ECT in the past 20 years. There were 2,916 patients in both cohorts, who were matched by age, sex, ethnicity, mood and behavioral disorders, endocrine disorders, intellectual disabilities, cerebrovascular disease, and other nervous system disorders. The mean age at treatment was 48.2 years, 38.5% were male, and 3.1% were Black or African American.

Short-term outcomes favored TMS, including the frequency of disorientation (0.41% vs 2.81%), retrograde amnesia (0.34% vs 0.65%), and headache (4.36% vs 7.20%). Long-term outcomes from 1 month to 5 years post treatment were also better in the TMS group, including depressive episodes (44.99% vs 53.77%), suicide attempts (3.98% vs 6.86%), and suicidal ideation (12.38% vs 23.49%). Kaplan-Meier curve analysis between 1 month and 5 years showed a benefit to TMS in probability of not experiencing a depressive episode, and not experiencing suicidal ideation.

“ECT has been the gold standard of treatment resistant depression for a long time, and it deserves to be. I think it’s something you should offer your patients. Not everyone might be comfortable with it, and if they’re not, I think it’s important to not stop the conversation there, but to offer something like TMS because TMS is something that might be more accessible to patients. It might be more affordable, and it might be less scary,” said Mr. Kandhadai

Mr. Kandhadai and Dr. Coslett have no relevant financial disclosures.

DENVER — Among patients with major depressive disorder, transcranial magnetic stimulation (TMS) had similar efficacy to electroconvulsive therapy (ECT), according to results from a retrospective study of patients treated in the past 20 years.

“We always learn in our textbooks that after about two or three medication trials is when you can start exploring more serious treatment protocols, such as ECT or TMS, but a lot of these patients weren’t going forward with it, and I was curious about it. I figured that TMS, which is a less expensive, less scary procedure that patients would more likely be open to, that is also approved for treatment resistant depression, would be a good alternative to ECT,” said Anuttham Kandhadai, a third-year medical student at University of Texas Medical Branch at Galveston, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
 

Study Findings Lead to More Questions

The researchers found lower rates of depressive episodes, suicidal attempts, and suicidal ideation among patients treated with TMS, but an important limitation was that the researchers did not know the severity of the depression in the two patient groups, according to Branch Coslett, MD, who attended the session and has performed research with TMS to treat aphasia in stroke patients. “I think it’s a very interesting study, and certainly something worth pursuing, but given that ECT is only used as a last resort, whereas TMS is often used as a second-line therapy, I think you’re really talking about very different populations that have had these treatments,” said Dr. Coslett.

Mr. Kandhadai recognized the limitations of the study and looks forward to expanding the research. “I’d love to explore cost effectiveness of the treatments. I’d love to explore patient familiarity and patient comfort with different treatments. And I’d also love to explore a more controlled study that can determine how severe someone’s depression is, and then be able to control for that and explore the outcomes based on the treatment protocol,” he said.

The ideal comparative study would be prospective, “but that will never be done. One Flew Over the Cuckoo’s Nest and similar sources of information have really poisoned the well,” said Dr. Coslett. However, he noted that advances have been made in ECT, and that targeting the right hemisphere produces fewer side effects: “The outcomes from unilateral right hemisphere stimulation are said to be every bit as good or maybe better, and you don’t get the confusion, you don’t get the memory loss, you don’t get all that sort of stuff that you’d expect when somebody has a prolonged, generalized tonic-clonic seizure.”

Still, people are naturally reluctant to undergo ECT. “I’ve seen it. It’s pretty barbaric. It’s better now and at my institution, people do get it, but they really, really have to be intractable,” he said.
 

Comparing Treatment Options

Mr. Kandhadai and his co-authors used the TriNetX database to identify patients with treatment-resistant major depressive disorder who received TMS or ECT in the past 20 years. There were 2,916 patients in both cohorts, who were matched by age, sex, ethnicity, mood and behavioral disorders, endocrine disorders, intellectual disabilities, cerebrovascular disease, and other nervous system disorders. The mean age at treatment was 48.2 years, 38.5% were male, and 3.1% were Black or African American.

Short-term outcomes favored TMS, including the frequency of disorientation (0.41% vs 2.81%), retrograde amnesia (0.34% vs 0.65%), and headache (4.36% vs 7.20%). Long-term outcomes from 1 month to 5 years post treatment were also better in the TMS group, including depressive episodes (44.99% vs 53.77%), suicide attempts (3.98% vs 6.86%), and suicidal ideation (12.38% vs 23.49%). Kaplan-Meier curve analysis between 1 month and 5 years showed a benefit to TMS in probability of not experiencing a depressive episode, and not experiencing suicidal ideation.

“ECT has been the gold standard of treatment resistant depression for a long time, and it deserves to be. I think it’s something you should offer your patients. Not everyone might be comfortable with it, and if they’re not, I think it’s important to not stop the conversation there, but to offer something like TMS because TMS is something that might be more accessible to patients. It might be more affordable, and it might be less scary,” said Mr. Kandhadai

Mr. Kandhadai and Dr. Coslett have no relevant financial disclosures.

DENVER — A first-in-class monoclonal antibody (riliprubart, Sanofi) that inhibits complement activation showed good activity versus IVIG in chronic inflammatory demyelinating polyneuropathy (CIDP), with good results in treatment-refractory and treatment-naive patients, according to results from a phase 2 clinical trial.

‘Impressive’ Results

The results were impressive, especially given that riliprubart outperformed IVIG, according to Frank Tennigkeit, PhD, senior director of pediatric development rare diseases at UCB Biosciences, who attended the session at the 2024 annual meeting of the American Academy of Neurology, where the study was presented. “There are few trials on CIDP, and the standard data are IVIG data.

“This is really amazing, especially in refractory patients. I turned to my neighbor [during the presentation] and said, ‘I’ve never seen CIDP data that good in my life. It works in all kinds of different patient populations, and also on the refractory ones. That’s what you want. That’s where the need is. And you saw a consistent effect and a strong effect on top of standard of care,” said Dr. Tennigkeit.

“It’s impressive. The only problem with CIDP is that it’s very difficult to compare treatments, because everyone has a different outcome. This was an open-label study, so there’s always a confounding bias. The proof of the pudding is going to be in a phase 3 blinded, randomized trial, but what I really admire about them, and I thought was very gutsy, is that they’re going head-to-head versus IVIG. I haven’t seen anyone who’s done that yet [in CIDP],” said Shalom Patole, MD, an internist and telehealth consultant in India, who also attended the session.
 

An Open-Label Phase 2 Study

The study had a somewhat unique design, according to Richard Lewis, MD, who presented the results. It was an open-label design that examined three subpopulations: 25 who had objective response to treatments (standard of care [SOC]–treated, mean age, 58.2 years; 80% male), 18 refractory patients who had been off treatment for up to 12 weeks (SOC-refractory, mean age, 63.9 years; 61% male), and 12 patients who had not been treated at all for at least 6 months or were treatment-naive (SOC-naive, mean age, 59.1 years; 67% male).

At 24 weeks, “if you looked at the treated group, 88% of those patients improved to remain stable, and only 12% relapsed. Most significantly, these patients who had responded to their IVIG, who were supposedly doing pretty well, 44% of those actually got better, so they improved from what would have been a pretty good baseline. The refractory patients, despite flunking the other treatments, 50% actually passed or improved with the treatment, so a significant response rate in a group that was not responding so well,” said Dr. Lewis, who is a neurologist at Cedars Sinai Medical Center.

The researchers also found that treatment with riliprubart led to inhibition of complement activity and a trend in reduction in neurofilament light chain levels by week 24 in all three groups.

Treatment-emergent adverse events occurred in 60% of the SOC-treated group, 72% of the SOC-refractory group, and 75% of the SOC-naive group, though grade 3 or higher events were rare (4%, 17%, and 8%, respectively). There was one death in the SOC-treated group and one in the SOC-refractory group. Both patients were elderly and had comorbid conditions.
 

Challenging the Current Standard of Care

The data have led to two additional phase 3 trials, one in refractory patients (Mobilize), and another for patients treated with IVIG who have residual disability (Vitalize). Sanofi is also planning a phase 3, placebo-controlled trial with one arm that will compare the antibody to IVIG, “which is a pretty ambitious trial design,” admitted Dr. Lewis.

Such a strategy is risky, but it could represent a big payoff for Sanofi if the phase 3 studies replicate the phase 2 studies. “No one would be using IVIG anymore if you beat IVIG by 50%. That will be the standard. If you do the trial [versus IVIG], you have a higher risk, but if you win it, you will win big,” said Dr. Tennigkeit.

The study was funded by Sanofi. Dr. Lewis has financial relationships with CSL Behring, Grifols, Pfizer, Sanofi, Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, Nuvig, Dianthus, Janssen, Medscape, Alexion, Alnylam, and Novartis. Dr. Tennigkeit is an employee of UCB Biosciences. Dr. Patole has no relevant financial disclosures.

DENVER — A first-in-class monoclonal antibody (riliprubart, Sanofi) that inhibits complement activation showed good activity versus IVIG in chronic inflammatory demyelinating polyneuropathy (CIDP), with good results in treatment-refractory and treatment-naive patients, according to results from a phase 2 clinical trial.

‘Impressive’ Results

The results were impressive, especially given that riliprubart outperformed IVIG, according to Frank Tennigkeit, PhD, senior director of pediatric development rare diseases at UCB Biosciences, who attended the session at the 2024 annual meeting of the American Academy of Neurology, where the study was presented. “There are few trials on CIDP, and the standard data are IVIG data.

“This is really amazing, especially in refractory patients. I turned to my neighbor [during the presentation] and said, ‘I’ve never seen CIDP data that good in my life. It works in all kinds of different patient populations, and also on the refractory ones. That’s what you want. That’s where the need is. And you saw a consistent effect and a strong effect on top of standard of care,” said Dr. Tennigkeit.

“It’s impressive. The only problem with CIDP is that it’s very difficult to compare treatments, because everyone has a different outcome. This was an open-label study, so there’s always a confounding bias. The proof of the pudding is going to be in a phase 3 blinded, randomized trial, but what I really admire about them, and I thought was very gutsy, is that they’re going head-to-head versus IVIG. I haven’t seen anyone who’s done that yet [in CIDP],” said Shalom Patole, MD, an internist and telehealth consultant in India, who also attended the session.
 

An Open-Label Phase 2 Study

The study had a somewhat unique design, according to Richard Lewis, MD, who presented the results. It was an open-label design that examined three subpopulations: 25 who had objective response to treatments (standard of care [SOC]–treated, mean age, 58.2 years; 80% male), 18 refractory patients who had been off treatment for up to 12 weeks (SOC-refractory, mean age, 63.9 years; 61% male), and 12 patients who had not been treated at all for at least 6 months or were treatment-naive (SOC-naive, mean age, 59.1 years; 67% male).

At 24 weeks, “if you looked at the treated group, 88% of those patients improved to remain stable, and only 12% relapsed. Most significantly, these patients who had responded to their IVIG, who were supposedly doing pretty well, 44% of those actually got better, so they improved from what would have been a pretty good baseline. The refractory patients, despite flunking the other treatments, 50% actually passed or improved with the treatment, so a significant response rate in a group that was not responding so well,” said Dr. Lewis, who is a neurologist at Cedars Sinai Medical Center.

The researchers also found that treatment with riliprubart led to inhibition of complement activity and a trend in reduction in neurofilament light chain levels by week 24 in all three groups.

Treatment-emergent adverse events occurred in 60% of the SOC-treated group, 72% of the SOC-refractory group, and 75% of the SOC-naive group, though grade 3 or higher events were rare (4%, 17%, and 8%, respectively). There was one death in the SOC-treated group and one in the SOC-refractory group. Both patients were elderly and had comorbid conditions.
 

Challenging the Current Standard of Care

The data have led to two additional phase 3 trials, one in refractory patients (Mobilize), and another for patients treated with IVIG who have residual disability (Vitalize). Sanofi is also planning a phase 3, placebo-controlled trial with one arm that will compare the antibody to IVIG, “which is a pretty ambitious trial design,” admitted Dr. Lewis.

Such a strategy is risky, but it could represent a big payoff for Sanofi if the phase 3 studies replicate the phase 2 studies. “No one would be using IVIG anymore if you beat IVIG by 50%. That will be the standard. If you do the trial [versus IVIG], you have a higher risk, but if you win it, you will win big,” said Dr. Tennigkeit.

The study was funded by Sanofi. Dr. Lewis has financial relationships with CSL Behring, Grifols, Pfizer, Sanofi, Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, Nuvig, Dianthus, Janssen, Medscape, Alexion, Alnylam, and Novartis. Dr. Tennigkeit is an employee of UCB Biosciences. Dr. Patole has no relevant financial disclosures.

DENVER — A first-in-class monoclonal antibody (riliprubart, Sanofi) that inhibits complement activation showed good activity versus IVIG in chronic inflammatory demyelinating polyneuropathy (CIDP), with good results in treatment-refractory and treatment-naive patients, according to results from a phase 2 clinical trial.

‘Impressive’ Results

The results were impressive, especially given that riliprubart outperformed IVIG, according to Frank Tennigkeit, PhD, senior director of pediatric development rare diseases at UCB Biosciences, who attended the session at the 2024 annual meeting of the American Academy of Neurology, where the study was presented. “There are few trials on CIDP, and the standard data are IVIG data.

“This is really amazing, especially in refractory patients. I turned to my neighbor [during the presentation] and said, ‘I’ve never seen CIDP data that good in my life. It works in all kinds of different patient populations, and also on the refractory ones. That’s what you want. That’s where the need is. And you saw a consistent effect and a strong effect on top of standard of care,” said Dr. Tennigkeit.

“It’s impressive. The only problem with CIDP is that it’s very difficult to compare treatments, because everyone has a different outcome. This was an open-label study, so there’s always a confounding bias. The proof of the pudding is going to be in a phase 3 blinded, randomized trial, but what I really admire about them, and I thought was very gutsy, is that they’re going head-to-head versus IVIG. I haven’t seen anyone who’s done that yet [in CIDP],” said Shalom Patole, MD, an internist and telehealth consultant in India, who also attended the session.
 

An Open-Label Phase 2 Study

The study had a somewhat unique design, according to Richard Lewis, MD, who presented the results. It was an open-label design that examined three subpopulations: 25 who had objective response to treatments (standard of care [SOC]–treated, mean age, 58.2 years; 80% male), 18 refractory patients who had been off treatment for up to 12 weeks (SOC-refractory, mean age, 63.9 years; 61% male), and 12 patients who had not been treated at all for at least 6 months or were treatment-naive (SOC-naive, mean age, 59.1 years; 67% male).

At 24 weeks, “if you looked at the treated group, 88% of those patients improved to remain stable, and only 12% relapsed. Most significantly, these patients who had responded to their IVIG, who were supposedly doing pretty well, 44% of those actually got better, so they improved from what would have been a pretty good baseline. The refractory patients, despite flunking the other treatments, 50% actually passed or improved with the treatment, so a significant response rate in a group that was not responding so well,” said Dr. Lewis, who is a neurologist at Cedars Sinai Medical Center.

The researchers also found that treatment with riliprubart led to inhibition of complement activity and a trend in reduction in neurofilament light chain levels by week 24 in all three groups.

Treatment-emergent adverse events occurred in 60% of the SOC-treated group, 72% of the SOC-refractory group, and 75% of the SOC-naive group, though grade 3 or higher events were rare (4%, 17%, and 8%, respectively). There was one death in the SOC-treated group and one in the SOC-refractory group. Both patients were elderly and had comorbid conditions.
 

Challenging the Current Standard of Care

The data have led to two additional phase 3 trials, one in refractory patients (Mobilize), and another for patients treated with IVIG who have residual disability (Vitalize). Sanofi is also planning a phase 3, placebo-controlled trial with one arm that will compare the antibody to IVIG, “which is a pretty ambitious trial design,” admitted Dr. Lewis.

Such a strategy is risky, but it could represent a big payoff for Sanofi if the phase 3 studies replicate the phase 2 studies. “No one would be using IVIG anymore if you beat IVIG by 50%. That will be the standard. If you do the trial [versus IVIG], you have a higher risk, but if you win it, you will win big,” said Dr. Tennigkeit.

The study was funded by Sanofi. Dr. Lewis has financial relationships with CSL Behring, Grifols, Pfizer, Sanofi, Argenx, Pharnext, Roche, Johnson & Johnson, Takeda, Boehringer Ingelheim, Nuvig, Dianthus, Janssen, Medscape, Alexion, Alnylam, and Novartis. Dr. Tennigkeit is an employee of UCB Biosciences. Dr. Patole has no relevant financial disclosures.