Neurology Reviews

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.

Recently, “low field” MRIs have been in the news, with the promise that they’ll be safer and easier. People can go in them with their cell phones, car keys in pockets, no ear plugs needed for the noise, etc. They’re cheaper to build and can be plugged into a standard outlet.

That’s all well and good, but what about accuracy and image quality?

That’s a big question. Even proponents of the technology say it’s not as good as what we see with 3T MRI, so they’re trying to compensate by using AI and other software protocols to enhance the pictures. Allegedly it looks good, but so far only healthy volunteers have been scanned. How will it do with a small low-grade glioma or other subtle (but important) findings? We don’t know yet.

Personally, I think having to give up your iPhone and car keys for an hour, and put in foam ear plugs, are small trade-offs to get an accurate diagnosis.

Of course, I’m also approaching this as someone who deals with brain imaging. Maybe for other structures, like a knee, that kind of detail isn’t as necessary (or maybe it is. I’m definitely not in that field).

So, as with so many things that make it into the popular press, they likely have potential, but are still not ready for prime time.

This sort of stuff always gets my office phones ringing. Patients see a blurb about it on the news or Facebook and assume it’s available now, so they want one. They seem to think the new MRI is like Bones McCoy’s tricorder. I take the scanner off my belt, wave it over them, and the answer comes up on the screen. The fact that the unit still weighs over a ton is hidden at the bottom of the blurb, if it’s even mentioned at all.

There’s also the likelihood that this sort of thing is going to be taken to the public, in the same way carotid Dopplers have been. Marketed to the worried well with celebrity endorsements and taglines like “see what your doctor won’t look for.” Of course, MRIs are chock full of things like nonspecific white matter changes, disc bulges, tiny meningiomas, and a host of other incidental findings that cause panic in cyberchondriacs. Who then call us.

But that’s another story.

I understand that for some parts of the world a comparatively inexpensive, transportable, MRI that requires less shielding and power is a HUGE deal. Its availability can make the difference between life and death.

I’m not knocking the technology. I’m sure it will be useful. But, like so much in medicine, it’s not here yet.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Recently, “low field” MRIs have been in the news, with the promise that they’ll be safer and easier. People can go in them with their cell phones, car keys in pockets, no ear plugs needed for the noise, etc. They’re cheaper to build and can be plugged into a standard outlet.

That’s all well and good, but what about accuracy and image quality?

That’s a big question. Even proponents of the technology say it’s not as good as what we see with 3T MRI, so they’re trying to compensate by using AI and other software protocols to enhance the pictures. Allegedly it looks good, but so far only healthy volunteers have been scanned. How will it do with a small low-grade glioma or other subtle (but important) findings? We don’t know yet.

Personally, I think having to give up your iPhone and car keys for an hour, and put in foam ear plugs, are small trade-offs to get an accurate diagnosis.

Of course, I’m also approaching this as someone who deals with brain imaging. Maybe for other structures, like a knee, that kind of detail isn’t as necessary (or maybe it is. I’m definitely not in that field).

So, as with so many things that make it into the popular press, they likely have potential, but are still not ready for prime time.

This sort of stuff always gets my office phones ringing. Patients see a blurb about it on the news or Facebook and assume it’s available now, so they want one. They seem to think the new MRI is like Bones McCoy’s tricorder. I take the scanner off my belt, wave it over them, and the answer comes up on the screen. The fact that the unit still weighs over a ton is hidden at the bottom of the blurb, if it’s even mentioned at all.

There’s also the likelihood that this sort of thing is going to be taken to the public, in the same way carotid Dopplers have been. Marketed to the worried well with celebrity endorsements and taglines like “see what your doctor won’t look for.” Of course, MRIs are chock full of things like nonspecific white matter changes, disc bulges, tiny meningiomas, and a host of other incidental findings that cause panic in cyberchondriacs. Who then call us.

But that’s another story.

I understand that for some parts of the world a comparatively inexpensive, transportable, MRI that requires less shielding and power is a HUGE deal. Its availability can make the difference between life and death.

I’m not knocking the technology. I’m sure it will be useful. But, like so much in medicine, it’s not here yet.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Recently, “low field” MRIs have been in the news, with the promise that they’ll be safer and easier. People can go in them with their cell phones, car keys in pockets, no ear plugs needed for the noise, etc. They’re cheaper to build and can be plugged into a standard outlet.

That’s all well and good, but what about accuracy and image quality?

That’s a big question. Even proponents of the technology say it’s not as good as what we see with 3T MRI, so they’re trying to compensate by using AI and other software protocols to enhance the pictures. Allegedly it looks good, but so far only healthy volunteers have been scanned. How will it do with a small low-grade glioma or other subtle (but important) findings? We don’t know yet.

Personally, I think having to give up your iPhone and car keys for an hour, and put in foam ear plugs, are small trade-offs to get an accurate diagnosis.

Of course, I’m also approaching this as someone who deals with brain imaging. Maybe for other structures, like a knee, that kind of detail isn’t as necessary (or maybe it is. I’m definitely not in that field).

So, as with so many things that make it into the popular press, they likely have potential, but are still not ready for prime time.

This sort of stuff always gets my office phones ringing. Patients see a blurb about it on the news or Facebook and assume it’s available now, so they want one. They seem to think the new MRI is like Bones McCoy’s tricorder. I take the scanner off my belt, wave it over them, and the answer comes up on the screen. The fact that the unit still weighs over a ton is hidden at the bottom of the blurb, if it’s even mentioned at all.

There’s also the likelihood that this sort of thing is going to be taken to the public, in the same way carotid Dopplers have been. Marketed to the worried well with celebrity endorsements and taglines like “see what your doctor won’t look for.” Of course, MRIs are chock full of things like nonspecific white matter changes, disc bulges, tiny meningiomas, and a host of other incidental findings that cause panic in cyberchondriacs. Who then call us.

But that’s another story.

I understand that for some parts of the world a comparatively inexpensive, transportable, MRI that requires less shielding and power is a HUGE deal. Its availability can make the difference between life and death.

I’m not knocking the technology. I’m sure it will be useful. But, like so much in medicine, it’s not here yet.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

As the availability of potential biomarkers for Parkinson’s disease drives the debate around diagnosing prodromal Parkinson’s disease (pPD) from theory to practice, said authors of a recent study, clinicians should weigh each patient’s preferences, circumstances, and goals against the potential benefits and harms of disclosure. The study and an accompanying editorial appeared online in Neurology.

Because markers such as SNCA, LRRK2, and GBA mutations impact small subgroups of patients at risk of developing monogenic forms of Parkinson’s disease, wrote Richard N. Rees, MBChB, MD, from the Department of Clinical and Movement Neurosciences at University College London Queen Square Institute of Neurology, and colleagues, researchers are working to identify people at risk of idiopathic Parkinson’s disease using models based on known risk and protective factors. The recent development of highly accurate cerebrospinal fluid (and potentially serum) alpha-synuclein seed amplification assays, which may show Parkinson’s disease’s signature before overt symptoms appear, will reinforce these efforts, authors added.
 

‘Tap the Brakes’

However, sources interviewed by Neurology Reviews counseled caution with potential prodromal Parkinson’s disease biomarkers. “As the science advances in Parkinson’s disease and related disorders,” said Michael S. Okun, MD, “our ability to predict who will and will not be diagnosed will improve. We should, however, tap the brakes and consider the consequences of making a diagnosis in someone at risk — especially someone without symptoms.” Dr. Okun is National Medical Advisor to the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health in Gainesville, Florida. He was not involved with the study.

Neurologists should ask themselves why they are testing for Parkinson’s disease biomarkers, said Dr. Okun, and what counseling and shared decision-making they provided beforehand. “This already complex scenario becomes even more complicated when we consider that many people with GBA gene mutations and some with LRRK2 mutations may never actually manifest Parkinson’s disease.”

A Holistic Approach to Shared Decision-Making

To avoid needlessly scaring patients, Dr. Hoy suggested broaching the topic of Parkinson’s disease biomarkers during advance care planning. “In the same conversation that you might talk about establishing surrogate decision-makers or potential do-not-resuscitate/intubate orders, you can talk about the potential of predictive testing, which is becoming more prevalent across domains of clinical practice.”

Understanding each patient’s values, preferences, and priorities requires a holistic approach, he said. “In the context of prodromal Parkinson’s disease, the benefits of enrolling in a new clinical trial or implementing lifestyle changes might vary depending on the person. Do you think this person would be likely to enroll in a clinical trial or implement those lifestyle changes?” Additionally, he recommended considering how a patient might react to a false diagnosis.

Whereas a diagnosis of mild cognitive impairment might not lead to Alzheimer’s disease or dementia, wrote Dr. Rees and colleagues, growing evidence including a review published in Neurology in 2022 supports the accuracy of alpha-synuclein seed amplification assays in detecting both established and prodromal Parkinson’s disease. For people thusly diagnosed, Dr. Rees and colleagues wrote, the psychosocial burden of inevitable progression could create feelings of helplessness, possibly undermining benefits of early knowledge.

Beyond patients’ reactions, said Dr. Hoy, a diagnosis of prodromal Parkinson’s disease could result in social stigma, changes to interpersonal relationships, or discrimination. “Understanding the implications and uncertainties of potential disclosure, relative to what a person would want to know or might be able to do about it, will be the key for deciding when is the right time,” he said.
 

Supporting Primary Care

As the shared decision-making burden likely will fall to primary care providers, Dr. Hoy added, neurologists should prioritize increasing these providers’ capacity to advise and refer patients appropriately. Although it is too soon to develop clinical guidelines, he said, neurologists could help educate such providers about pPD and the growing availability of promising biomarkers.

“Parkinson’s is thought of as a movement disorder first and foremost,” said Dr. Hoy. However, various non-motor symptoms including sleep problems, depression, anxiety, apathy, constipation, and gastrointestinal issues often appear before movement-related symptoms during the prodromal phase.

As potentially the first line of defense against prodromal Parkinson’s disease, primary care providers also should know the distinction between early and timely diagnosis, added Dr. Hoy. Introduced by Dr. Rees and colleagues in a 2018 review published in F1000Research, timely diagnosis balances patient preferences, the availability and efficacy of DMT, and health systems’ ability to support and manage individuals at every stage of disease.

The current study was funded by a Parkinson’s UK grant (which paid Dr. Rees’s salary). The editorial was supported by a National Institute of Mental Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative award, a grant from the National Institute on Aging, and a Wellcome Discovery Award. Dr. Hoy reported no relevant disclosures.

As the availability of potential biomarkers for Parkinson’s disease drives the debate around diagnosing prodromal Parkinson’s disease (pPD) from theory to practice, said authors of a recent study, clinicians should weigh each patient’s preferences, circumstances, and goals against the potential benefits and harms of disclosure. The study and an accompanying editorial appeared online in Neurology.

Because markers such as SNCA, LRRK2, and GBA mutations impact small subgroups of patients at risk of developing monogenic forms of Parkinson’s disease, wrote Richard N. Rees, MBChB, MD, from the Department of Clinical and Movement Neurosciences at University College London Queen Square Institute of Neurology, and colleagues, researchers are working to identify people at risk of idiopathic Parkinson’s disease using models based on known risk and protective factors. The recent development of highly accurate cerebrospinal fluid (and potentially serum) alpha-synuclein seed amplification assays, which may show Parkinson’s disease’s signature before overt symptoms appear, will reinforce these efforts, authors added.
 

‘Tap the Brakes’

However, sources interviewed by Neurology Reviews counseled caution with potential prodromal Parkinson’s disease biomarkers. “As the science advances in Parkinson’s disease and related disorders,” said Michael S. Okun, MD, “our ability to predict who will and will not be diagnosed will improve. We should, however, tap the brakes and consider the consequences of making a diagnosis in someone at risk — especially someone without symptoms.” Dr. Okun is National Medical Advisor to the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health in Gainesville, Florida. He was not involved with the study.

Neurologists should ask themselves why they are testing for Parkinson’s disease biomarkers, said Dr. Okun, and what counseling and shared decision-making they provided beforehand. “This already complex scenario becomes even more complicated when we consider that many people with GBA gene mutations and some with LRRK2 mutations may never actually manifest Parkinson’s disease.”

A Holistic Approach to Shared Decision-Making

To avoid needlessly scaring patients, Dr. Hoy suggested broaching the topic of Parkinson’s disease biomarkers during advance care planning. “In the same conversation that you might talk about establishing surrogate decision-makers or potential do-not-resuscitate/intubate orders, you can talk about the potential of predictive testing, which is becoming more prevalent across domains of clinical practice.”

Understanding each patient’s values, preferences, and priorities requires a holistic approach, he said. “In the context of prodromal Parkinson’s disease, the benefits of enrolling in a new clinical trial or implementing lifestyle changes might vary depending on the person. Do you think this person would be likely to enroll in a clinical trial or implement those lifestyle changes?” Additionally, he recommended considering how a patient might react to a false diagnosis.

Whereas a diagnosis of mild cognitive impairment might not lead to Alzheimer’s disease or dementia, wrote Dr. Rees and colleagues, growing evidence including a review published in Neurology in 2022 supports the accuracy of alpha-synuclein seed amplification assays in detecting both established and prodromal Parkinson’s disease. For people thusly diagnosed, Dr. Rees and colleagues wrote, the psychosocial burden of inevitable progression could create feelings of helplessness, possibly undermining benefits of early knowledge.

Beyond patients’ reactions, said Dr. Hoy, a diagnosis of prodromal Parkinson’s disease could result in social stigma, changes to interpersonal relationships, or discrimination. “Understanding the implications and uncertainties of potential disclosure, relative to what a person would want to know or might be able to do about it, will be the key for deciding when is the right time,” he said.
 

Supporting Primary Care

As the shared decision-making burden likely will fall to primary care providers, Dr. Hoy added, neurologists should prioritize increasing these providers’ capacity to advise and refer patients appropriately. Although it is too soon to develop clinical guidelines, he said, neurologists could help educate such providers about pPD and the growing availability of promising biomarkers.

“Parkinson’s is thought of as a movement disorder first and foremost,” said Dr. Hoy. However, various non-motor symptoms including sleep problems, depression, anxiety, apathy, constipation, and gastrointestinal issues often appear before movement-related symptoms during the prodromal phase.

As potentially the first line of defense against prodromal Parkinson’s disease, primary care providers also should know the distinction between early and timely diagnosis, added Dr. Hoy. Introduced by Dr. Rees and colleagues in a 2018 review published in F1000Research, timely diagnosis balances patient preferences, the availability and efficacy of DMT, and health systems’ ability to support and manage individuals at every stage of disease.

The current study was funded by a Parkinson’s UK grant (which paid Dr. Rees’s salary). The editorial was supported by a National Institute of Mental Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative award, a grant from the National Institute on Aging, and a Wellcome Discovery Award. Dr. Hoy reported no relevant disclosures.

As the availability of potential biomarkers for Parkinson’s disease drives the debate around diagnosing prodromal Parkinson’s disease (pPD) from theory to practice, said authors of a recent study, clinicians should weigh each patient’s preferences, circumstances, and goals against the potential benefits and harms of disclosure. The study and an accompanying editorial appeared online in Neurology.

Because markers such as SNCA, LRRK2, and GBA mutations impact small subgroups of patients at risk of developing monogenic forms of Parkinson’s disease, wrote Richard N. Rees, MBChB, MD, from the Department of Clinical and Movement Neurosciences at University College London Queen Square Institute of Neurology, and colleagues, researchers are working to identify people at risk of idiopathic Parkinson’s disease using models based on known risk and protective factors. The recent development of highly accurate cerebrospinal fluid (and potentially serum) alpha-synuclein seed amplification assays, which may show Parkinson’s disease’s signature before overt symptoms appear, will reinforce these efforts, authors added.
 

‘Tap the Brakes’

However, sources interviewed by Neurology Reviews counseled caution with potential prodromal Parkinson’s disease biomarkers. “As the science advances in Parkinson’s disease and related disorders,” said Michael S. Okun, MD, “our ability to predict who will and will not be diagnosed will improve. We should, however, tap the brakes and consider the consequences of making a diagnosis in someone at risk — especially someone without symptoms.” Dr. Okun is National Medical Advisor to the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health in Gainesville, Florida. He was not involved with the study.

Neurologists should ask themselves why they are testing for Parkinson’s disease biomarkers, said Dr. Okun, and what counseling and shared decision-making they provided beforehand. “This already complex scenario becomes even more complicated when we consider that many people with GBA gene mutations and some with LRRK2 mutations may never actually manifest Parkinson’s disease.”

A Holistic Approach to Shared Decision-Making

To avoid needlessly scaring patients, Dr. Hoy suggested broaching the topic of Parkinson’s disease biomarkers during advance care planning. “In the same conversation that you might talk about establishing surrogate decision-makers or potential do-not-resuscitate/intubate orders, you can talk about the potential of predictive testing, which is becoming more prevalent across domains of clinical practice.”

Understanding each patient’s values, preferences, and priorities requires a holistic approach, he said. “In the context of prodromal Parkinson’s disease, the benefits of enrolling in a new clinical trial or implementing lifestyle changes might vary depending on the person. Do you think this person would be likely to enroll in a clinical trial or implement those lifestyle changes?” Additionally, he recommended considering how a patient might react to a false diagnosis.

Whereas a diagnosis of mild cognitive impairment might not lead to Alzheimer’s disease or dementia, wrote Dr. Rees and colleagues, growing evidence including a review published in Neurology in 2022 supports the accuracy of alpha-synuclein seed amplification assays in detecting both established and prodromal Parkinson’s disease. For people thusly diagnosed, Dr. Rees and colleagues wrote, the psychosocial burden of inevitable progression could create feelings of helplessness, possibly undermining benefits of early knowledge.

Beyond patients’ reactions, said Dr. Hoy, a diagnosis of prodromal Parkinson’s disease could result in social stigma, changes to interpersonal relationships, or discrimination. “Understanding the implications and uncertainties of potential disclosure, relative to what a person would want to know or might be able to do about it, will be the key for deciding when is the right time,” he said.
 

Supporting Primary Care

As the shared decision-making burden likely will fall to primary care providers, Dr. Hoy added, neurologists should prioritize increasing these providers’ capacity to advise and refer patients appropriately. Although it is too soon to develop clinical guidelines, he said, neurologists could help educate such providers about pPD and the growing availability of promising biomarkers.

“Parkinson’s is thought of as a movement disorder first and foremost,” said Dr. Hoy. However, various non-motor symptoms including sleep problems, depression, anxiety, apathy, constipation, and gastrointestinal issues often appear before movement-related symptoms during the prodromal phase.

As potentially the first line of defense against prodromal Parkinson’s disease, primary care providers also should know the distinction between early and timely diagnosis, added Dr. Hoy. Introduced by Dr. Rees and colleagues in a 2018 review published in F1000Research, timely diagnosis balances patient preferences, the availability and efficacy of DMT, and health systems’ ability to support and manage individuals at every stage of disease.

The current study was funded by a Parkinson’s UK grant (which paid Dr. Rees’s salary). The editorial was supported by a National Institute of Mental Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative award, a grant from the National Institute on Aging, and a Wellcome Discovery Award. Dr. Hoy reported no relevant 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 — 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.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.

“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.

The results were presented at the European Stroke Organization Conference (ESOC) 2024.

Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.

Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.

The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.

Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.

Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.

The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.

Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.

Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.

In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
 

A Novel Target for Stroke Treatment

In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.

In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).

“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.

He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.

“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.

Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.

“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.

“I think we have a new tool, but of course we need further trials to confirm that,” she added.

The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.

“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.

The results were presented at the European Stroke Organization Conference (ESOC) 2024.

Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.

Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.

The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.

Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.

Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.

The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.

Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.

Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.

In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
 

A Novel Target for Stroke Treatment

In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.

In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).

“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.

He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.

“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.

Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.

“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.

“I think we have a new tool, but of course we need further trials to confirm that,” she added.

The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.

“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.

The results were presented at the European Stroke Organization Conference (ESOC) 2024.

Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.

Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.

The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.

Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.

Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.

The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.

Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.

Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.

In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
 

A Novel Target for Stroke Treatment

In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.

In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).

“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.

He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.

“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.

Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.

“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.

“I think we have a new tool, but of course we need further trials to confirm that,” she added.

The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

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.

The envelope was a small one, with a handwritten address. Of course, there were other things in the mail to sort through: insurance payments, bills, correspondence. So I attended to those while I made coffee and started my computer.

After a few minutes I came back to the small envelope.

Inside was a card from a recently widowed lady, thanking me for my care of her husband and telling me I was very kind.

I’d only seem him once, about a year ago, and then had a follow-up phone call to go over the results.

In medicine you develop, as I’ve previously written, “Spidey Sense.” Things alert you that something bad is going on, even when you can’t quite put your finger on it yet. His story set off several of my alarms, and I sent him off for tests.

A few days later the electromyography and nerve conduction velocity (EMG/NCV) specialist I’d referred him to called to confirm the gentleman had ALS. He’d given him the diagnosis and started him on riluzole.

I called the patient and his wife that night to discuss things in more detail. My colleague, since neuromuscular disease is his field, had already started the process (this isn’t patient poaching, he and I have worked together long enough that he knows I’d rather he take over the case). I explained things further. They didn’t have any questions.

I didn’t hear from them again until the card came. On the flip side was a picture of them and their extended family. I have no idea how they vote, or what their religion is, or how much money they have. None of that matters.

They’re nice people, and a patient, who came to me for help. I was touched by her appreciation for the little I could do, and that she took time to express that to me.

None of us cures anyone in the long run. We can put off the inevitable, do our best to relieve suffering, and try to bring comfort — even when the last is all we can do.

Here in 2024, with all of our medications and computers and tests it’s hard to believe that we still come up short — very short – against so many diseases. Yet we do.

All of us can only do our best, even when the best we can do is to be kind.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

The envelope was a small one, with a handwritten address. Of course, there were other things in the mail to sort through: insurance payments, bills, correspondence. So I attended to those while I made coffee and started my computer.

After a few minutes I came back to the small envelope.

Inside was a card from a recently widowed lady, thanking me for my care of her husband and telling me I was very kind.

I’d only seem him once, about a year ago, and then had a follow-up phone call to go over the results.

In medicine you develop, as I’ve previously written, “Spidey Sense.” Things alert you that something bad is going on, even when you can’t quite put your finger on it yet. His story set off several of my alarms, and I sent him off for tests.

A few days later the electromyography and nerve conduction velocity (EMG/NCV) specialist I’d referred him to called to confirm the gentleman had ALS. He’d given him the diagnosis and started him on riluzole.

I called the patient and his wife that night to discuss things in more detail. My colleague, since neuromuscular disease is his field, had already started the process (this isn’t patient poaching, he and I have worked together long enough that he knows I’d rather he take over the case). I explained things further. They didn’t have any questions.

I didn’t hear from them again until the card came. On the flip side was a picture of them and their extended family. I have no idea how they vote, or what their religion is, or how much money they have. None of that matters.

They’re nice people, and a patient, who came to me for help. I was touched by her appreciation for the little I could do, and that she took time to express that to me.

None of us cures anyone in the long run. We can put off the inevitable, do our best to relieve suffering, and try to bring comfort — even when the last is all we can do.

Here in 2024, with all of our medications and computers and tests it’s hard to believe that we still come up short — very short – against so many diseases. Yet we do.

All of us can only do our best, even when the best we can do is to be kind.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

The envelope was a small one, with a handwritten address. Of course, there were other things in the mail to sort through: insurance payments, bills, correspondence. So I attended to those while I made coffee and started my computer.

After a few minutes I came back to the small envelope.

Inside was a card from a recently widowed lady, thanking me for my care of her husband and telling me I was very kind.

I’d only seem him once, about a year ago, and then had a follow-up phone call to go over the results.

In medicine you develop, as I’ve previously written, “Spidey Sense.” Things alert you that something bad is going on, even when you can’t quite put your finger on it yet. His story set off several of my alarms, and I sent him off for tests.

A few days later the electromyography and nerve conduction velocity (EMG/NCV) specialist I’d referred him to called to confirm the gentleman had ALS. He’d given him the diagnosis and started him on riluzole.

I called the patient and his wife that night to discuss things in more detail. My colleague, since neuromuscular disease is his field, had already started the process (this isn’t patient poaching, he and I have worked together long enough that he knows I’d rather he take over the case). I explained things further. They didn’t have any questions.

I didn’t hear from them again until the card came. On the flip side was a picture of them and their extended family. I have no idea how they vote, or what their religion is, or how much money they have. None of that matters.

They’re nice people, and a patient, who came to me for help. I was touched by her appreciation for the little I could do, and that she took time to express that to me.

None of us cures anyone in the long run. We can put off the inevitable, do our best to relieve suffering, and try to bring comfort — even when the last is all we can do.

Here in 2024, with all of our medications and computers and tests it’s hard to believe that we still come up short — very short – against so many diseases. Yet we do.

All of us can only do our best, even when the best we can do is to be kind.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

About 45,000 people will descend on Chicago for the American Society of Clinical Oncology (ASCO) annual meeting, starting May 31.

From its origins in 1964, ASCO’s annual event has grown to become the world’s largest clinical oncology meeting, drawing attendees from across the globe.

More than 7000 abstracts were submitted for this year’s meeting a new record — and over 5000 were selected for presentation.

This year’s chair of the Annual Meeting Education Committee, Thomas William LeBlanc, MD, told us he has been attending the meeting since his training days more than a decade ago.

The event is “just incredibly empowering and energizing,” Dr. LeBlanc said, with opportunities to catch up with old colleagues and meet new ones, learn how far oncology has come and where it’s headed, and hear clinical pearls to take back the clinic.

This year’s theme, selected by ASCO President Lynn M. Schuchter, MD, is “The Art and Science of Cancer Care: From Comfort to Cure.” 

Dr. LeBlanc, a blood cancer specialist at Duke University, Durham, North Carolina, said the theme has been woven throughout the abstract and educational sessions. Most sessions will have at least one presentation related to how we support people — not only “when we cure them but also when we can’t cure them,” he said.

Topics will include patient well-being, comfort measures, and survivorship. And for the first time the plenary session will include a palliative care abstract that addresses whether or not palliative care can be delivered effectively through telemedicine. The session is on Sunday, June 2. 

Other potentially practice changing plenary abstracts tackle immunotherapy combinations for resectable melanoma, perioperative chemotherapy vs neoadjuvant chemoradiation for esophageal cancer, and osimertinib after definitive chemoradiotherapy for unresectable non–small cell lung cancer.

ASCO is piloting a slightly different format for research presentations this year. Instead of starting with context and background, speakers have been asked to present study results upfront as well as repeat them at the end of the talk. The reason behind the tweak is that engagement and retention tend to be better when results are presented upfront, instead of just at the end of a talk.

A popular session — ASCO Voices — has also been given a more central position in the conference: Friday, May 31. In this session, speakers will give short presentations about their personal experiences as providers, researchers, or patients.

ASCO Voices is a relatively recent addition to the meeting that has grown and gotten better. The talks are usually “very powerful narratives” that remind clinicians about “the importance of what they’re doing each day,” Dr. LeBlanc said.

Snippets of the talks will be played while people wait for sessions to begin at the meeting, so attendees who miss the Friday talks can still hear them.

In terms of educational sessions, Dr. LeBlanc highlighted two that might be of general interest to practicing oncologists: A joint ASCO/American Association for Cancer Research session entitled “Drugging the ‘Undruggable’ Target: Successes, Challenges, and the Road Ahead,” on Sunday morning and “Common Sense Oncology: Equity, Value, and Outcomes That Matter” on Monday morning.

As a blood cancer specialist, he said he is particularly interested in the topline results from the ASC4FIRST trial of asciminib, a newer kinase inhibitor, in newly diagnosed chronic myeloid leukemia, presented on Friday.

As in past years, this news organization will be on hand providing coverage with a dedicated team of reporters, editors, and videographers. Stop by our exhibit hall booth — number 26030 — to learn about the tools we offer to support your practice.
 

A version of this article appeared on Medscape.com .

About 45,000 people will descend on Chicago for the American Society of Clinical Oncology (ASCO) annual meeting, starting May 31.

From its origins in 1964, ASCO’s annual event has grown to become the world’s largest clinical oncology meeting, drawing attendees from across the globe.

More than 7000 abstracts were submitted for this year’s meeting a new record — and over 5000 were selected for presentation.

This year’s chair of the Annual Meeting Education Committee, Thomas William LeBlanc, MD, told us he has been attending the meeting since his training days more than a decade ago.

The event is “just incredibly empowering and energizing,” Dr. LeBlanc said, with opportunities to catch up with old colleagues and meet new ones, learn how far oncology has come and where it’s headed, and hear clinical pearls to take back the clinic.

This year’s theme, selected by ASCO President Lynn M. Schuchter, MD, is “The Art and Science of Cancer Care: From Comfort to Cure.” 

Dr. LeBlanc, a blood cancer specialist at Duke University, Durham, North Carolina, said the theme has been woven throughout the abstract and educational sessions. Most sessions will have at least one presentation related to how we support people — not only “when we cure them but also when we can’t cure them,” he said.

Topics will include patient well-being, comfort measures, and survivorship. And for the first time the plenary session will include a palliative care abstract that addresses whether or not palliative care can be delivered effectively through telemedicine. The session is on Sunday, June 2. 

Other potentially practice changing plenary abstracts tackle immunotherapy combinations for resectable melanoma, perioperative chemotherapy vs neoadjuvant chemoradiation for esophageal cancer, and osimertinib after definitive chemoradiotherapy for unresectable non–small cell lung cancer.

ASCO is piloting a slightly different format for research presentations this year. Instead of starting with context and background, speakers have been asked to present study results upfront as well as repeat them at the end of the talk. The reason behind the tweak is that engagement and retention tend to be better when results are presented upfront, instead of just at the end of a talk.

A popular session — ASCO Voices — has also been given a more central position in the conference: Friday, May 31. In this session, speakers will give short presentations about their personal experiences as providers, researchers, or patients.

ASCO Voices is a relatively recent addition to the meeting that has grown and gotten better. The talks are usually “very powerful narratives” that remind clinicians about “the importance of what they’re doing each day,” Dr. LeBlanc said.

Snippets of the talks will be played while people wait for sessions to begin at the meeting, so attendees who miss the Friday talks can still hear them.

In terms of educational sessions, Dr. LeBlanc highlighted two that might be of general interest to practicing oncologists: A joint ASCO/American Association for Cancer Research session entitled “Drugging the ‘Undruggable’ Target: Successes, Challenges, and the Road Ahead,” on Sunday morning and “Common Sense Oncology: Equity, Value, and Outcomes That Matter” on Monday morning.

As a blood cancer specialist, he said he is particularly interested in the topline results from the ASC4FIRST trial of asciminib, a newer kinase inhibitor, in newly diagnosed chronic myeloid leukemia, presented on Friday.

As in past years, this news organization will be on hand providing coverage with a dedicated team of reporters, editors, and videographers. Stop by our exhibit hall booth — number 26030 — to learn about the tools we offer to support your practice.
 

A version of this article appeared on Medscape.com .

About 45,000 people will descend on Chicago for the American Society of Clinical Oncology (ASCO) annual meeting, starting May 31.

From its origins in 1964, ASCO’s annual event has grown to become the world’s largest clinical oncology meeting, drawing attendees from across the globe.

More than 7000 abstracts were submitted for this year’s meeting a new record — and over 5000 were selected for presentation.

This year’s chair of the Annual Meeting Education Committee, Thomas William LeBlanc, MD, told us he has been attending the meeting since his training days more than a decade ago.

The event is “just incredibly empowering and energizing,” Dr. LeBlanc said, with opportunities to catch up with old colleagues and meet new ones, learn how far oncology has come and where it’s headed, and hear clinical pearls to take back the clinic.

This year’s theme, selected by ASCO President Lynn M. Schuchter, MD, is “The Art and Science of Cancer Care: From Comfort to Cure.” 

Dr. LeBlanc, a blood cancer specialist at Duke University, Durham, North Carolina, said the theme has been woven throughout the abstract and educational sessions. Most sessions will have at least one presentation related to how we support people — not only “when we cure them but also when we can’t cure them,” he said.

Topics will include patient well-being, comfort measures, and survivorship. And for the first time the plenary session will include a palliative care abstract that addresses whether or not palliative care can be delivered effectively through telemedicine. The session is on Sunday, June 2. 

Other potentially practice changing plenary abstracts tackle immunotherapy combinations for resectable melanoma, perioperative chemotherapy vs neoadjuvant chemoradiation for esophageal cancer, and osimertinib after definitive chemoradiotherapy for unresectable non–small cell lung cancer.

ASCO is piloting a slightly different format for research presentations this year. Instead of starting with context and background, speakers have been asked to present study results upfront as well as repeat them at the end of the talk. The reason behind the tweak is that engagement and retention tend to be better when results are presented upfront, instead of just at the end of a talk.

A popular session — ASCO Voices — has also been given a more central position in the conference: Friday, May 31. In this session, speakers will give short presentations about their personal experiences as providers, researchers, or patients.

ASCO Voices is a relatively recent addition to the meeting that has grown and gotten better. The talks are usually “very powerful narratives” that remind clinicians about “the importance of what they’re doing each day,” Dr. LeBlanc said.

Snippets of the talks will be played while people wait for sessions to begin at the meeting, so attendees who miss the Friday talks can still hear them.

In terms of educational sessions, Dr. LeBlanc highlighted two that might be of general interest to practicing oncologists: A joint ASCO/American Association for Cancer Research session entitled “Drugging the ‘Undruggable’ Target: Successes, Challenges, and the Road Ahead,” on Sunday morning and “Common Sense Oncology: Equity, Value, and Outcomes That Matter” on Monday morning.

As a blood cancer specialist, he said he is particularly interested in the topline results from the ASC4FIRST trial of asciminib, a newer kinase inhibitor, in newly diagnosed chronic myeloid leukemia, presented on Friday.

As in past years, this news organization will be on hand providing coverage with a dedicated team of reporters, editors, and videographers. Stop by our exhibit hall booth — number 26030 — to learn about the tools we offer to support your practice.
 

A version of this article appeared on Medscape.com .

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development. 

Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.

Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.

Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test. 

If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.

Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.

There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development. 

One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.

Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.

Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
 

A version of this article appeared on Medscape.com.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development. 

Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.

Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.

Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test. 

If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.

Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.

There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development. 

One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.

Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.

Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
 

A version of this article appeared on Medscape.com.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development. 

Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.

Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.

Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test. 

If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.

Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.

There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development. 

One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.

Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.

Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
 

A version of this article appeared on Medscape.com.