Neurology Reviews

PHOENIX – Artificial intelligence (AI) is poised to dramatically alter health care, and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.

Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.

He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.

Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.

It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.

Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
 

Trust, but verify

Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.

AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
 

Limitations

The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.

Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.

Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.

There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.

Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.

Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.

He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.

For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”

Dr. Morren has no relevant financial disclosures.

PHOENIX – Artificial intelligence (AI) is poised to dramatically alter health care, and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.

Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.

He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.

Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.

It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.

Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
 

Trust, but verify

Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.

AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
 

Limitations

The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.

Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.

Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.

There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.

Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.

Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.

He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.

For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”

Dr. Morren has no relevant financial disclosures.

PHOENIX – Artificial intelligence (AI) is poised to dramatically alter health care, and it presents opportunities for increased production and automation of some tasks. However, it is prone to error and ‘hallucinations’ despite an authoritative tone, so its conclusions must be verified.

Those were some of the messages from a talk by John Morren, MD, an associate professor of neurology at Case Western Reserve University, Cleveland, who spoke about AI at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

He encouraged attendees to get involved in the conversation of AI, because it is here to stay and will have a big impact on health care. “If we’re not around the table making decisions, decisions will be made for us in our absence and won’t be in our favor,” said Dr. Morren.

He started out his talk by asking if anyone in the room had used AI. After about half raised their hands, he countered that nearly everyone likely had. Voice assistants like SIRI and Alexa, social media with curated feeds, online shopping tools that provide product suggestions, and content recommendations from streaming services like Netflix all rely on AI technology.

Within medicine, AI is already playing a role in various fields, including medical imaging, disease diagnosis, drug discovery and development, predictive analytics, personalized medicine, telemedicine, and health care management.

It also has potential to be used on the job. For example, ChatGPT can generate and refine conversations towards a specific length, format, style, and level of detail. Alternatives include Bing AI from Microsoft, Bard AI from Google, Writesonic, Copy.ai, SpinBot, HIX.AI, and Chatsonic.

Specific to medicine, Consensus is a search engine that uses AI to search for, summarize, and synthesize studies from peer-reviewed literature.
 

Trust, but verify

Dr. Morren presented some specific use cases, including patient education and responses to patient inquiries, as well as generating letters to insurance companies appealing denial of coverage claims. He also showed an example where he asked Bing AI to explain to a patient, at a sixth- to seventh-grade reading level, the red-flag symptoms of myasthenic crisis.

AI can generate summaries of clinical evidence of previous studies. Asked by this reporter how to trust the accuracies of the summaries if the user hasn’t thoroughly read the papers, he acknowledged the imperfection of AI. “I would say that if you’re going to make a decision that you would not have made normally based on the summary that it’s giving, if you can find the fact that you’re anchoring the decision on, go into the article yourself and make sure that it’s well vetted. The AI is just good to tap you on your shoulder and say, ‘hey, just consider this.’ That’s all it is. You should always trust, but verify. If the AI is forcing you to say something new that you would not say, maybe don’t do it – or at least research it to know that it’s the truth and then you elevate yourself and get yourself to the next level.”
 

Limitations

The need to verify can create its own burden, according to one attendee. “I often find I end up spending more time verifying [what ChatGPT has provided]. This seems to take more time than a traditional way of going to PubMed or UpToDate or any of the other human generated consensus way,” he said.

Dr. Morren replied that he wouldn’t recommend using ChatGPT to query medical literature. Instead he recommended Consensus, which only searches the peer-reviewed medical literature.

Another key limitation is that most AI programs are date limited: For example, ChatGPT doesn’t include information after September 2021, though this may change with paid subscriptions. He also starkly warned the audience to never enter sensitive information, including patient identifiers.

There are legal and ethical considerations to AI. Dr. Morren warned against overreliance on AI, as this could undermine compassion and lead to erosion of trust, which makes it important to disclose any use of AI-generated content.

Another attendee raised concerns that AI may be generating research content, including slides for presentations, abstracts, titles, or article text. Dr. Morren said that some organizations, such as the International Committee of Medical Journal Editors, have incorporated AI in their recommendations, stating that authors should disclose any contributions of AI to their publications. However, there is little that can be done to identify AI-generated content, leaving it up to the honor code.

Asked to make predictions about how AI will evolve in the clinic over the next 2-3 years, Dr. Morren suggested that it will likely be embedded in electronic medical records. He anticipated that it will save physicians time so that they can spend more time interacting directly with patients. He quoted Eric Topol, MD, professor of medicine at Scripps Research Translational Institute, La Jolla, Calif., as saying that AI could save 20% of a physician’s time, which could be spent with patients. Dr. Morren saw it differently. “I know where that 20% of time liberated is going to go. I’m going to see 20% more patients. I’m a realist,” he said, to audience laughter.

He also predicted that AI will be found in wearables and devices, allowing health care to expand into the patient’s home in real time. “A lot of what we’re wearing is going to be an extension of the doctor’s office,” he said.

For those hoping for more guidance, Dr. Morren noted that he is the chairman of the professional practice committee of AANEM, and the group will be putting out a position statement within the next couple of months. “It will be a little bit of a blueprint for the path going forward. There are specific things that need to be done. In research, for example, you have to ensure that datasets are diverse enough. To do that we need to have inter-institutional collaboration. We have to ensure patient privacy. Consent for this needs to be a little more explicit because this is a novel area. Those are things that need to be stipulated and ratified through a task force.”

Dr. Morren has no relevant financial disclosures.

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group, compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”

He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.

Target organ damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”

The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.

Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”

So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”

Public health priority

It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First definitive evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.

Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.

The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group, compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”

He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.

Target organ damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”

The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.

Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”

So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”

Public health priority

It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First definitive evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.

Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.

The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.

All-cause dementia, the primary outcome, was significantly reduced by 15% in the intervention group, compared with usual care, and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.

“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”

He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.

Target organ damage

Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”

The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.

Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”

So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”

Public health priority

It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”

Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.

This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.

It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.

Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.

All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.

The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.

Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.

Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.

At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.

The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.

Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.

The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.

At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.

The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).

Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.

Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.

The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.

First definitive evidence

Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.

The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.

Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”

Since it is the first of its kind though, replication of the results will be important, he noted.

The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.

The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

I am not a marketing person. I never will be. I don’t think like one.

A current article on FiercePharma talked about Boehringer Ingelheim’s recent “rebranding,” which involved (among other things) changing the blues in its logo and ads to greens.

Maybe someone else out there would notice that change, but I wouldn’t have if I hadn’t read about it. Nor am I sure what affect it would have on me, if any. But I’m sure they paid psychologists and marketing teams quite a bit to make sure it was a good idea.

Likewise, when AbbVie repackaged Ubrelvy from 10 to a package to 16, the company felt the need to change the design of the sample boxes (which are also now green). I’m pretty sure none of my patients noticed. The only reason I did is because I’m the one who stocks my sample shelf here.

Abbvie and Boehringer aren’t alone in this, of course. Pharmaceutical marketing is big business. I understand the companies want doctors and patients to know about their products. In that respect they’re no different from General Motors or Kellogg’s.

But pharmaceuticals fall into a different area. Kellogg’s products don’t require a middleman handing you a script allowing you to buy corn flakes, so although the products are sold to the public, they also have to be sold to a person who isn’t buying them – the prescriber.

Not all these ads are bad, of course. At best they raise public awareness of different health conditions and the options to treat them. At worst ... well, currently there are several movies out there about the results of marketing done by the Sackler family and Purdue.

To me, most pharmaceutical ads look the same. They show happy people going about their lives, with the impression being that they couldn’t have done this without the benefit of the drug being marketed.

To a large extent I can’t knock that. Pharmaceuticals are amazing things. They’ve contributed dramatically to human health, life quality, and longevity.

But would I, or most people, notice if the lettering in the ads were blue, green, or yellow? Probably not. Someone with a background in the psychology of marketing would be able to show me data on how different colors affect our perceptions, but I still look at this and wonder if the money could have been better spent.

Maybe that’s why I’m not in marketing. I tend to be on the practical side. The idea of hiring a celebrity to endorse a migraine (or pretty much any) medication would never have occurred to me. I have no idea how much Pfizer paid Lady Gaga to sell Nurtec, but I’m pretty sure it’s a lot more than I’ll earn this year. Probably ever.

Like most neurologists I’m hopelessly left-brained. But I still wonder how much things like this really make a difference.

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

I am not a marketing person. I never will be. I don’t think like one.

A current article on FiercePharma talked about Boehringer Ingelheim’s recent “rebranding,” which involved (among other things) changing the blues in its logo and ads to greens.

Maybe someone else out there would notice that change, but I wouldn’t have if I hadn’t read about it. Nor am I sure what affect it would have on me, if any. But I’m sure they paid psychologists and marketing teams quite a bit to make sure it was a good idea.

Likewise, when AbbVie repackaged Ubrelvy from 10 to a package to 16, the company felt the need to change the design of the sample boxes (which are also now green). I’m pretty sure none of my patients noticed. The only reason I did is because I’m the one who stocks my sample shelf here.

Abbvie and Boehringer aren’t alone in this, of course. Pharmaceutical marketing is big business. I understand the companies want doctors and patients to know about their products. In that respect they’re no different from General Motors or Kellogg’s.

But pharmaceuticals fall into a different area. Kellogg’s products don’t require a middleman handing you a script allowing you to buy corn flakes, so although the products are sold to the public, they also have to be sold to a person who isn’t buying them – the prescriber.

Not all these ads are bad, of course. At best they raise public awareness of different health conditions and the options to treat them. At worst ... well, currently there are several movies out there about the results of marketing done by the Sackler family and Purdue.

To me, most pharmaceutical ads look the same. They show happy people going about their lives, with the impression being that they couldn’t have done this without the benefit of the drug being marketed.

To a large extent I can’t knock that. Pharmaceuticals are amazing things. They’ve contributed dramatically to human health, life quality, and longevity.

But would I, or most people, notice if the lettering in the ads were blue, green, or yellow? Probably not. Someone with a background in the psychology of marketing would be able to show me data on how different colors affect our perceptions, but I still look at this and wonder if the money could have been better spent.

Maybe that’s why I’m not in marketing. I tend to be on the practical side. The idea of hiring a celebrity to endorse a migraine (or pretty much any) medication would never have occurred to me. I have no idea how much Pfizer paid Lady Gaga to sell Nurtec, but I’m pretty sure it’s a lot more than I’ll earn this year. Probably ever.

Like most neurologists I’m hopelessly left-brained. But I still wonder how much things like this really make a difference.

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

I am not a marketing person. I never will be. I don’t think like one.

A current article on FiercePharma talked about Boehringer Ingelheim’s recent “rebranding,” which involved (among other things) changing the blues in its logo and ads to greens.

Maybe someone else out there would notice that change, but I wouldn’t have if I hadn’t read about it. Nor am I sure what affect it would have on me, if any. But I’m sure they paid psychologists and marketing teams quite a bit to make sure it was a good idea.

Likewise, when AbbVie repackaged Ubrelvy from 10 to a package to 16, the company felt the need to change the design of the sample boxes (which are also now green). I’m pretty sure none of my patients noticed. The only reason I did is because I’m the one who stocks my sample shelf here.

Abbvie and Boehringer aren’t alone in this, of course. Pharmaceutical marketing is big business. I understand the companies want doctors and patients to know about their products. In that respect they’re no different from General Motors or Kellogg’s.

But pharmaceuticals fall into a different area. Kellogg’s products don’t require a middleman handing you a script allowing you to buy corn flakes, so although the products are sold to the public, they also have to be sold to a person who isn’t buying them – the prescriber.

Not all these ads are bad, of course. At best they raise public awareness of different health conditions and the options to treat them. At worst ... well, currently there are several movies out there about the results of marketing done by the Sackler family and Purdue.

To me, most pharmaceutical ads look the same. They show happy people going about their lives, with the impression being that they couldn’t have done this without the benefit of the drug being marketed.

To a large extent I can’t knock that. Pharmaceuticals are amazing things. They’ve contributed dramatically to human health, life quality, and longevity.

But would I, or most people, notice if the lettering in the ads were blue, green, or yellow? Probably not. Someone with a background in the psychology of marketing would be able to show me data on how different colors affect our perceptions, but I still look at this and wonder if the money could have been better spent.

Maybe that’s why I’m not in marketing. I tend to be on the practical side. The idea of hiring a celebrity to endorse a migraine (or pretty much any) medication would never have occurred to me. I have no idea how much Pfizer paid Lady Gaga to sell Nurtec, but I’m pretty sure it’s a lot more than I’ll earn this year. Probably ever.

Like most neurologists I’m hopelessly left-brained. But I still wonder how much things like this really make a difference.

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

TOPLINE:

A combination of tocilizumab (Actemra) and 8 weeks of tapering prednisone was effective for inducing and maintaining disease remission in adults with giant cell arteritis (GCA).

METHODOLOGY:

• In a single-center, single-arm, open-label pilot study, 30 adults (mean age, 73.7 years) with GCA received 162 mg of tocilizumab as a subcutaneous injection once a week for 52 weeks, plus prednisone starting between 20 mg and 60 mg with a prespecified 8-week taper off the glucocorticoid.
• Patients had to be at least 50 years of age and could have either new-onset (diagnosis within 6 weeks of baseline) or relapsing disease (diagnosis > 6 weeks from baseline).
• The primary endpoint was sustained, prednisone-free remission at 52 weeks, defined by an erythrocyte sedimentation rate of less than 40 mm/h, C-reactive protein level less than 10 mg/L, and adherence to the prednisone taper; secondary endpoints included the proportions of patients in remission and relapse, cumulative prednisone dose, and glucocorticoid toxicity.

TAKEAWAY:

• At 52 weeks, 23 patients (77%) met the criteria for sustained remission after weaning off prednisone within 8 weeks of starting tocilizumab; 7 relapsed after a mean of 15.8 weeks.
• Of the patients who relapsed, six underwent a second prednisone taper for 8 weeks with a mean initial daily dose of 32.1 mg, four regained and maintained remission, and two experienced a second relapse and withdrew from the study.
• The mean cumulative prednisone dose at week 52 was 1,051.5 mg for responders and 1,673.1 mg for nonresponders.
• All 30 patients had at least one adverse event; four patients had a serious adverse event likely related to tocilizumab, prednisone, or both.

IN PRACTICE:

Studies such as this “are highly valuable as proof of concept, but of course cannot be definitive guides to treatment decisions without a comparator group,” according to authors of an editorial accompanying the study.

SOURCE:

The study, by Sebastian Unizony, MD, Harvard Medical School, Boston, and colleagues, was published in The Lancet Rheumatology .

LIMITATIONS:

The small size and open-label design with no control group were limiting factors; more research is needed to confirm the findings before this treatment strategy can be recommended for clinical practice.

DISCLOSURES:

The study was funded by Genentech. Two authors reported financial relationships with pharmaceutical companies outside of this report.

A version of this article first appeared on Medscape.com.

TOPLINE:

A combination of tocilizumab (Actemra) and 8 weeks of tapering prednisone was effective for inducing and maintaining disease remission in adults with giant cell arteritis (GCA).

METHODOLOGY:

• In a single-center, single-arm, open-label pilot study, 30 adults (mean age, 73.7 years) with GCA received 162 mg of tocilizumab as a subcutaneous injection once a week for 52 weeks, plus prednisone starting between 20 mg and 60 mg with a prespecified 8-week taper off the glucocorticoid.
• Patients had to be at least 50 years of age and could have either new-onset (diagnosis within 6 weeks of baseline) or relapsing disease (diagnosis > 6 weeks from baseline).
• The primary endpoint was sustained, prednisone-free remission at 52 weeks, defined by an erythrocyte sedimentation rate of less than 40 mm/h, C-reactive protein level less than 10 mg/L, and adherence to the prednisone taper; secondary endpoints included the proportions of patients in remission and relapse, cumulative prednisone dose, and glucocorticoid toxicity.

TAKEAWAY:

• At 52 weeks, 23 patients (77%) met the criteria for sustained remission after weaning off prednisone within 8 weeks of starting tocilizumab; 7 relapsed after a mean of 15.8 weeks.
• Of the patients who relapsed, six underwent a second prednisone taper for 8 weeks with a mean initial daily dose of 32.1 mg, four regained and maintained remission, and two experienced a second relapse and withdrew from the study.
• The mean cumulative prednisone dose at week 52 was 1,051.5 mg for responders and 1,673.1 mg for nonresponders.
• All 30 patients had at least one adverse event; four patients had a serious adverse event likely related to tocilizumab, prednisone, or both.

IN PRACTICE:

Studies such as this “are highly valuable as proof of concept, but of course cannot be definitive guides to treatment decisions without a comparator group,” according to authors of an editorial accompanying the study.

SOURCE:

The study, by Sebastian Unizony, MD, Harvard Medical School, Boston, and colleagues, was published in The Lancet Rheumatology .

LIMITATIONS:

The small size and open-label design with no control group were limiting factors; more research is needed to confirm the findings before this treatment strategy can be recommended for clinical practice.

DISCLOSURES:

The study was funded by Genentech. Two authors reported financial relationships with pharmaceutical companies outside of this report.

A version of this article first appeared on Medscape.com.

TOPLINE:

A combination of tocilizumab (Actemra) and 8 weeks of tapering prednisone was effective for inducing and maintaining disease remission in adults with giant cell arteritis (GCA).

METHODOLOGY:

• In a single-center, single-arm, open-label pilot study, 30 adults (mean age, 73.7 years) with GCA received 162 mg of tocilizumab as a subcutaneous injection once a week for 52 weeks, plus prednisone starting between 20 mg and 60 mg with a prespecified 8-week taper off the glucocorticoid.
• Patients had to be at least 50 years of age and could have either new-onset (diagnosis within 6 weeks of baseline) or relapsing disease (diagnosis > 6 weeks from baseline).
• The primary endpoint was sustained, prednisone-free remission at 52 weeks, defined by an erythrocyte sedimentation rate of less than 40 mm/h, C-reactive protein level less than 10 mg/L, and adherence to the prednisone taper; secondary endpoints included the proportions of patients in remission and relapse, cumulative prednisone dose, and glucocorticoid toxicity.

TAKEAWAY:

• At 52 weeks, 23 patients (77%) met the criteria for sustained remission after weaning off prednisone within 8 weeks of starting tocilizumab; 7 relapsed after a mean of 15.8 weeks.
• Of the patients who relapsed, six underwent a second prednisone taper for 8 weeks with a mean initial daily dose of 32.1 mg, four regained and maintained remission, and two experienced a second relapse and withdrew from the study.
• The mean cumulative prednisone dose at week 52 was 1,051.5 mg for responders and 1,673.1 mg for nonresponders.
• All 30 patients had at least one adverse event; four patients had a serious adverse event likely related to tocilizumab, prednisone, or both.

IN PRACTICE:

Studies such as this “are highly valuable as proof of concept, but of course cannot be definitive guides to treatment decisions without a comparator group,” according to authors of an editorial accompanying the study.

SOURCE:

The study, by Sebastian Unizony, MD, Harvard Medical School, Boston, and colleagues, was published in The Lancet Rheumatology .

LIMITATIONS:

The small size and open-label design with no control group were limiting factors; more research is needed to confirm the findings before this treatment strategy can be recommended for clinical practice.

DISCLOSURES:

The study was funded by Genentech. Two authors reported financial relationships with pharmaceutical companies outside of this report.

A version of this article first appeared on Medscape.com.

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

A version of this article first appeared on Medscape.com.

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

A version of this article first appeared on Medscape.com.

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

A version of this article first appeared on Medscape.com.

Neurologic music therapy (NMT), a specially designed intervention targeting movement, balance, and cognitive functioning, improves depressive symptoms and increases brain-derived neurotrophic factor (BDNF), early results of a small study suggest.

“We’re really happy with the results,” said lead study author psychotherapist Honey Bryant, a PhD candidate and research assistant at the Centre for Neuroscience Studies, Queen’s University, Kingston, Ont.

“We showed neurologic music therapy improves mental health and increases neuroplasticity, when used in conjunction with stroke rehabilitation.”

The findings were presented at the virtual XXVI World Congress of Neurology.
 

Moving with music

With improved stroke survival rates and longer life expectancy, there’s an increasing need for effective post-stroke interventions for neurocognitive impairments and mood disorders, the authors noted.

NMT is an evidence-based treatment system that uses elements of music such as rhythm, melody, and tempo to treat various brain conditions. A trained NMT therapist uses standardized techniques to address goals in the areas of speech, movement, and cognition.

The intervention is not new – it’s been around for a few decades – but there are “minimal papers on NMT and nothing on stroke rehabilitation used in the way we did it,” said Ms. Bryant.

The study included 57 patients, mean age 75 years, receiving rehabilitation following a stroke who were randomly assigned to NMT or passive music listening.

In the NMT group, a music therapist asked participants to choose music beforehand and integrated this into each session.

“Each day was different,” said Ms. Bryant. “For example, if it involved motor movement, the music therapist would say, ‘When I sing this word, raise your arm up.’ For Johnny Cash’s ‘Ring of Fire,’ we made our arms into a circle.”

She explained that the rhythm and timing of the music can affect the motor system and other areas of the brain.

Those in the passive music group listened to a curated list of calming classical and relaxing spa music.

Both groups were offered five 45-minute sessions per week for 2 weeks.

Among other things, researchers used the Hospital Anxiety and Depression Scale (HADS), administered a semistructured interview, and collected blood samples to determine levels of cortisol and BDNF.

After the 2-week intervention, the researchers found participants in the NMT group had a significant mean decrease in depression.

They also had increased cortisol levels, which is not unexpected after a stroke, especially with increased anxiety linked to financial and other stressors, said Ms. Bryant, adding these levels should decrease with treatment.

Recipients of the NMT had significant increases in BDNF, a neurotrophin that plays an important role in neuronal survival and growth, but only in those who attended several consecutive sessions.
 

Increased plasticity

“We see greater increases in plasticity when the therapy is used intensively, meaning at least four treatments consecutively,” said Ms. Bryant. Participants in the NMT group also reported they “overall felt well,” she added.

She noted NMT can be tailored to individual deficit, “so you can make it solely for motor movement or you can make it solely for language.”

Next steps could include more closely targeting the music to individual preferences and investigating whether the benefits of the intervention extend to other types of brain injury, for example traumatic brain injury, which typically affects younger people, said Ms. Bryant.

“In this study, participants were older and there was an unknown; a lot of them were going back into the community but didn’t know if it was into a retirement home or long-term care.”

It’s unclear if the benefits are sustained after the intervention stops, she said.

There are also the issues of cost and accessibility; in Kingston, there are few music therapists certified in the area of NMT.

Ms. Bryant hopes NMT is eventually included in stroke rehabilitation. “Stroke therapy is typically very intensive on its own; you’re doing it every single day for about a month or 6 weeks,” she said. “It would be interesting to see whether we would see a shorter hospital stay if this is included in stroke rehab.”

Asked to comment, Michael H. Thaut, PhD, professor, faculty of music and faculty of medicine, and Canada research chair in music, neuroscience and health at the University of Toronto, said while these data are preliminary, “they do extend the benefits of NMT in stroke rehabilitation, especially measuring BDNF in addition to having behavioral data.”

However, it’s “unfortunate” the poster didn’t specify which cognitive intervention techniques were used in the study, said Dr. Thaut. “There are nine coded techniques in NMT, including for attention, memory, psychosocial function, and executive function.”

His own study, published in NeuroRehabilitation, focused on training for motor goals in stroke patients. It showed that NMT benefited cognitive functioning and affective responses.

The study was funded by a Queen’s University Research Initiation Grant. Ms. Bryant and Dr. Thaut have not disclosed any relevant financial relationships.

A version of this article first appeared on Medscape.com.

Neurologic music therapy (NMT), a specially designed intervention targeting movement, balance, and cognitive functioning, improves depressive symptoms and increases brain-derived neurotrophic factor (BDNF), early results of a small study suggest.

“We’re really happy with the results,” said lead study author psychotherapist Honey Bryant, a PhD candidate and research assistant at the Centre for Neuroscience Studies, Queen’s University, Kingston, Ont.

“We showed neurologic music therapy improves mental health and increases neuroplasticity, when used in conjunction with stroke rehabilitation.”

The findings were presented at the virtual XXVI World Congress of Neurology.
 

Moving with music

With improved stroke survival rates and longer life expectancy, there’s an increasing need for effective post-stroke interventions for neurocognitive impairments and mood disorders, the authors noted.

NMT is an evidence-based treatment system that uses elements of music such as rhythm, melody, and tempo to treat various brain conditions. A trained NMT therapist uses standardized techniques to address goals in the areas of speech, movement, and cognition.

The intervention is not new – it’s been around for a few decades – but there are “minimal papers on NMT and nothing on stroke rehabilitation used in the way we did it,” said Ms. Bryant.

The study included 57 patients, mean age 75 years, receiving rehabilitation following a stroke who were randomly assigned to NMT or passive music listening.

In the NMT group, a music therapist asked participants to choose music beforehand and integrated this into each session.

“Each day was different,” said Ms. Bryant. “For example, if it involved motor movement, the music therapist would say, ‘When I sing this word, raise your arm up.’ For Johnny Cash’s ‘Ring of Fire,’ we made our arms into a circle.”

She explained that the rhythm and timing of the music can affect the motor system and other areas of the brain.

Those in the passive music group listened to a curated list of calming classical and relaxing spa music.

Both groups were offered five 45-minute sessions per week for 2 weeks.

Among other things, researchers used the Hospital Anxiety and Depression Scale (HADS), administered a semistructured interview, and collected blood samples to determine levels of cortisol and BDNF.

After the 2-week intervention, the researchers found participants in the NMT group had a significant mean decrease in depression.

They also had increased cortisol levels, which is not unexpected after a stroke, especially with increased anxiety linked to financial and other stressors, said Ms. Bryant, adding these levels should decrease with treatment.

Recipients of the NMT had significant increases in BDNF, a neurotrophin that plays an important role in neuronal survival and growth, but only in those who attended several consecutive sessions.
 

Increased plasticity

“We see greater increases in plasticity when the therapy is used intensively, meaning at least four treatments consecutively,” said Ms. Bryant. Participants in the NMT group also reported they “overall felt well,” she added.

She noted NMT can be tailored to individual deficit, “so you can make it solely for motor movement or you can make it solely for language.”

Next steps could include more closely targeting the music to individual preferences and investigating whether the benefits of the intervention extend to other types of brain injury, for example traumatic brain injury, which typically affects younger people, said Ms. Bryant.

“In this study, participants were older and there was an unknown; a lot of them were going back into the community but didn’t know if it was into a retirement home or long-term care.”

It’s unclear if the benefits are sustained after the intervention stops, she said.

There are also the issues of cost and accessibility; in Kingston, there are few music therapists certified in the area of NMT.

Ms. Bryant hopes NMT is eventually included in stroke rehabilitation. “Stroke therapy is typically very intensive on its own; you’re doing it every single day for about a month or 6 weeks,” she said. “It would be interesting to see whether we would see a shorter hospital stay if this is included in stroke rehab.”

Asked to comment, Michael H. Thaut, PhD, professor, faculty of music and faculty of medicine, and Canada research chair in music, neuroscience and health at the University of Toronto, said while these data are preliminary, “they do extend the benefits of NMT in stroke rehabilitation, especially measuring BDNF in addition to having behavioral data.”

However, it’s “unfortunate” the poster didn’t specify which cognitive intervention techniques were used in the study, said Dr. Thaut. “There are nine coded techniques in NMT, including for attention, memory, psychosocial function, and executive function.”

His own study, published in NeuroRehabilitation, focused on training for motor goals in stroke patients. It showed that NMT benefited cognitive functioning and affective responses.

The study was funded by a Queen’s University Research Initiation Grant. Ms. Bryant and Dr. Thaut have not disclosed any relevant financial relationships.

A version of this article first appeared on Medscape.com.

Neurologic music therapy (NMT), a specially designed intervention targeting movement, balance, and cognitive functioning, improves depressive symptoms and increases brain-derived neurotrophic factor (BDNF), early results of a small study suggest.

“We’re really happy with the results,” said lead study author psychotherapist Honey Bryant, a PhD candidate and research assistant at the Centre for Neuroscience Studies, Queen’s University, Kingston, Ont.

“We showed neurologic music therapy improves mental health and increases neuroplasticity, when used in conjunction with stroke rehabilitation.”

The findings were presented at the virtual XXVI World Congress of Neurology.
 

Moving with music

With improved stroke survival rates and longer life expectancy, there’s an increasing need for effective post-stroke interventions for neurocognitive impairments and mood disorders, the authors noted.

NMT is an evidence-based treatment system that uses elements of music such as rhythm, melody, and tempo to treat various brain conditions. A trained NMT therapist uses standardized techniques to address goals in the areas of speech, movement, and cognition.

The intervention is not new – it’s been around for a few decades – but there are “minimal papers on NMT and nothing on stroke rehabilitation used in the way we did it,” said Ms. Bryant.

The study included 57 patients, mean age 75 years, receiving rehabilitation following a stroke who were randomly assigned to NMT or passive music listening.

In the NMT group, a music therapist asked participants to choose music beforehand and integrated this into each session.

“Each day was different,” said Ms. Bryant. “For example, if it involved motor movement, the music therapist would say, ‘When I sing this word, raise your arm up.’ For Johnny Cash’s ‘Ring of Fire,’ we made our arms into a circle.”

She explained that the rhythm and timing of the music can affect the motor system and other areas of the brain.

Those in the passive music group listened to a curated list of calming classical and relaxing spa music.

Both groups were offered five 45-minute sessions per week for 2 weeks.

Among other things, researchers used the Hospital Anxiety and Depression Scale (HADS), administered a semistructured interview, and collected blood samples to determine levels of cortisol and BDNF.

After the 2-week intervention, the researchers found participants in the NMT group had a significant mean decrease in depression.

They also had increased cortisol levels, which is not unexpected after a stroke, especially with increased anxiety linked to financial and other stressors, said Ms. Bryant, adding these levels should decrease with treatment.

Recipients of the NMT had significant increases in BDNF, a neurotrophin that plays an important role in neuronal survival and growth, but only in those who attended several consecutive sessions.
 

Increased plasticity

“We see greater increases in plasticity when the therapy is used intensively, meaning at least four treatments consecutively,” said Ms. Bryant. Participants in the NMT group also reported they “overall felt well,” she added.

She noted NMT can be tailored to individual deficit, “so you can make it solely for motor movement or you can make it solely for language.”

Next steps could include more closely targeting the music to individual preferences and investigating whether the benefits of the intervention extend to other types of brain injury, for example traumatic brain injury, which typically affects younger people, said Ms. Bryant.

“In this study, participants were older and there was an unknown; a lot of them were going back into the community but didn’t know if it was into a retirement home or long-term care.”

It’s unclear if the benefits are sustained after the intervention stops, she said.

There are also the issues of cost and accessibility; in Kingston, there are few music therapists certified in the area of NMT.

Ms. Bryant hopes NMT is eventually included in stroke rehabilitation. “Stroke therapy is typically very intensive on its own; you’re doing it every single day for about a month or 6 weeks,” she said. “It would be interesting to see whether we would see a shorter hospital stay if this is included in stroke rehab.”

Asked to comment, Michael H. Thaut, PhD, professor, faculty of music and faculty of medicine, and Canada research chair in music, neuroscience and health at the University of Toronto, said while these data are preliminary, “they do extend the benefits of NMT in stroke rehabilitation, especially measuring BDNF in addition to having behavioral data.”

However, it’s “unfortunate” the poster didn’t specify which cognitive intervention techniques were used in the study, said Dr. Thaut. “There are nine coded techniques in NMT, including for attention, memory, psychosocial function, and executive function.”

His own study, published in NeuroRehabilitation, focused on training for motor goals in stroke patients. It showed that NMT benefited cognitive functioning and affective responses.

The study was funded by a Queen’s University Research Initiation Grant. Ms. Bryant and Dr. Thaut have not disclosed any relevant financial relationships.

A version of this article first appeared on Medscape.com.

PHOENIX – The prevalence of myasthenia gravis is about 0.13% among U.S. adults, and the condition is more common in Whites than in African Americans, according to a new analysis of the National Institutes of Health All of Us database. The prevalence is higher than what has been seen in other studies, which could represent a true difference in prevalence, or reflect limitations of the database.

Worldwide estimates suggest that myasthenia gravis affects 700,000 people globally, with incidence rates ranging between 6.3 and 29 per 1,000,000 person-years in Europe and a prevalence between 111.7 and 361 per 1,000,000. Data from Australia, Taiwan, and South Korea also show evidence of increased prevalence in recent years.

However, there is little data about the prevalence of myasthenia gravis in the United States, or about differences between racial groups, according to Bhaskar Roy, MBBS, who presented the study at the 2023 annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). He noted that most studies are outdated, and the most recent study focused on ocular myasthenia gravis.
 

True incidence or artifact?

The finding is surprising and may be an artifact of the immature nature of the All of Us database, according to Srikanth Muppidi, MD, who asked about the limitation during the Q&A session following the talk. “The incidence of 0.13 is definitely higher than what we would think would be the true incidence of myasthenia gravis from [clinical experience]. It’s possible that our understanding of true incidence is wrong and this is the actual incidence. What I would like them to do, and I think they’re trying to do, is to look at this finding [and compare it with] other more mature databases and other regional databases. One of the current challenges of All of Us is that our patients are basically being recruited from some parts of the country, and the middle of the country has hardly any presence in the database, so it becomes really challenging to understand it,” Dr. Muppidi said in an interview.

However, Dr. Muppidi, who is a clinical professor of neurology at Stanford (Calif.) Medicine, noted that the All of Us database is still growing. When it has recruited more patients with a diverse population, “it [will be a] valuable source for rare diseases to try to understand true incidence of those diseases,” he said.
 

Understanding the true prevalence

Dr. Roy recognized the geographic limitations of the database. “Some states, particularly Massachusetts, New York, and California, had a lot of patients in the database, where there were no patients from many states,” said Dr. Roy, associate professor of neurology at Yale University, New Haven, Conn.

He said that the group is working with other databases, including UK Biobank. “The goal is to incorporate all of these databases together [to determine the true incidence],” said Dr. Roy.

It’s critical to understand the true prevalence of myasthenia gravis since new therapies are in development and coming to market. “I worry that myasthenia gravis might be considered less common than it truly is, and that will limit growth of the field if the feeling is that there are not that many [myasthenia gravis patients] in the country,” said Dr. Muppidi.

The study included data from 369,297 adult patients, using Systematized Nomenclature of Medicine (SNOMED) and International Classification of Diseases (ICD) codes to identify patients with myasthenia gravis. There were 479 cases of myasthenia gravis, for a prevalence of 0.13 (95% confidence interval [CI], 0.12-0.14). Of myasthenia gravis patients, 65% were female and the mean age was 64 years. The prevalence of myasthenia gravis in White individuals was 0.16 (95% CI, 0.15-0.18), of which 63% were female, and the mean age was 66 years. The prevalence among Black individuals was 0.078 (95% CI, 0.060-0.10), with 77% of the population female and a mean age of 58 years. The prevalence in Hispanics was 0.091 (95% CI, 0.070-0.12), with 80% female and a mean age of 58 years. Among Asians, the prevalence was 0.056 (95% CI, 0.025-0.12) and 57% were female, with a mean age of 58 years.

The researchers also looked at the EXPLORE-MG database drawn from Yale (n = 3,269,000), which showed a much lower overall myasthenia gravis prevalence of 0.019 (95% CI, 0.017-0.020), a female proportion of 46.8%, and a mean age of 56.6 years. Notably, EXPLORE-MG had a lower proportion of women and a younger population than All of Us.

The researchers compared data from All of Us with other databases for other conditions. The prevalence of ALS was the same as in other conditions, while diabetic neuropathy was significantly lower (2.7 versus 28.5-50 among diabetic patients) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was higher (0.084 versus 0.028).

Dr. Muppidi has been on advisory boards for Alexion, Argenx, UBC, and Immunovant. Dr. Roy has consulted for Alexion, Takeda Pharmaceuticals, and Argenx and owns stock in Cabaletta Bio. He has received research support from Takeda, Abcuro, and Argenx.

PHOENIX – The prevalence of myasthenia gravis is about 0.13% among U.S. adults, and the condition is more common in Whites than in African Americans, according to a new analysis of the National Institutes of Health All of Us database. The prevalence is higher than what has been seen in other studies, which could represent a true difference in prevalence, or reflect limitations of the database.

Worldwide estimates suggest that myasthenia gravis affects 700,000 people globally, with incidence rates ranging between 6.3 and 29 per 1,000,000 person-years in Europe and a prevalence between 111.7 and 361 per 1,000,000. Data from Australia, Taiwan, and South Korea also show evidence of increased prevalence in recent years.

However, there is little data about the prevalence of myasthenia gravis in the United States, or about differences between racial groups, according to Bhaskar Roy, MBBS, who presented the study at the 2023 annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). He noted that most studies are outdated, and the most recent study focused on ocular myasthenia gravis.
 

True incidence or artifact?

The finding is surprising and may be an artifact of the immature nature of the All of Us database, according to Srikanth Muppidi, MD, who asked about the limitation during the Q&A session following the talk. “The incidence of 0.13 is definitely higher than what we would think would be the true incidence of myasthenia gravis from [clinical experience]. It’s possible that our understanding of true incidence is wrong and this is the actual incidence. What I would like them to do, and I think they’re trying to do, is to look at this finding [and compare it with] other more mature databases and other regional databases. One of the current challenges of All of Us is that our patients are basically being recruited from some parts of the country, and the middle of the country has hardly any presence in the database, so it becomes really challenging to understand it,” Dr. Muppidi said in an interview.

However, Dr. Muppidi, who is a clinical professor of neurology at Stanford (Calif.) Medicine, noted that the All of Us database is still growing. When it has recruited more patients with a diverse population, “it [will be a] valuable source for rare diseases to try to understand true incidence of those diseases,” he said.
 

Understanding the true prevalence

Dr. Roy recognized the geographic limitations of the database. “Some states, particularly Massachusetts, New York, and California, had a lot of patients in the database, where there were no patients from many states,” said Dr. Roy, associate professor of neurology at Yale University, New Haven, Conn.

He said that the group is working with other databases, including UK Biobank. “The goal is to incorporate all of these databases together [to determine the true incidence],” said Dr. Roy.

It’s critical to understand the true prevalence of myasthenia gravis since new therapies are in development and coming to market. “I worry that myasthenia gravis might be considered less common than it truly is, and that will limit growth of the field if the feeling is that there are not that many [myasthenia gravis patients] in the country,” said Dr. Muppidi.

The study included data from 369,297 adult patients, using Systematized Nomenclature of Medicine (SNOMED) and International Classification of Diseases (ICD) codes to identify patients with myasthenia gravis. There were 479 cases of myasthenia gravis, for a prevalence of 0.13 (95% confidence interval [CI], 0.12-0.14). Of myasthenia gravis patients, 65% were female and the mean age was 64 years. The prevalence of myasthenia gravis in White individuals was 0.16 (95% CI, 0.15-0.18), of which 63% were female, and the mean age was 66 years. The prevalence among Black individuals was 0.078 (95% CI, 0.060-0.10), with 77% of the population female and a mean age of 58 years. The prevalence in Hispanics was 0.091 (95% CI, 0.070-0.12), with 80% female and a mean age of 58 years. Among Asians, the prevalence was 0.056 (95% CI, 0.025-0.12) and 57% were female, with a mean age of 58 years.

The researchers also looked at the EXPLORE-MG database drawn from Yale (n = 3,269,000), which showed a much lower overall myasthenia gravis prevalence of 0.019 (95% CI, 0.017-0.020), a female proportion of 46.8%, and a mean age of 56.6 years. Notably, EXPLORE-MG had a lower proportion of women and a younger population than All of Us.

The researchers compared data from All of Us with other databases for other conditions. The prevalence of ALS was the same as in other conditions, while diabetic neuropathy was significantly lower (2.7 versus 28.5-50 among diabetic patients) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was higher (0.084 versus 0.028).

Dr. Muppidi has been on advisory boards for Alexion, Argenx, UBC, and Immunovant. Dr. Roy has consulted for Alexion, Takeda Pharmaceuticals, and Argenx and owns stock in Cabaletta Bio. He has received research support from Takeda, Abcuro, and Argenx.

PHOENIX – The prevalence of myasthenia gravis is about 0.13% among U.S. adults, and the condition is more common in Whites than in African Americans, according to a new analysis of the National Institutes of Health All of Us database. The prevalence is higher than what has been seen in other studies, which could represent a true difference in prevalence, or reflect limitations of the database.

Worldwide estimates suggest that myasthenia gravis affects 700,000 people globally, with incidence rates ranging between 6.3 and 29 per 1,000,000 person-years in Europe and a prevalence between 111.7 and 361 per 1,000,000. Data from Australia, Taiwan, and South Korea also show evidence of increased prevalence in recent years.

However, there is little data about the prevalence of myasthenia gravis in the United States, or about differences between racial groups, according to Bhaskar Roy, MBBS, who presented the study at the 2023 annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). He noted that most studies are outdated, and the most recent study focused on ocular myasthenia gravis.
 

True incidence or artifact?

The finding is surprising and may be an artifact of the immature nature of the All of Us database, according to Srikanth Muppidi, MD, who asked about the limitation during the Q&A session following the talk. “The incidence of 0.13 is definitely higher than what we would think would be the true incidence of myasthenia gravis from [clinical experience]. It’s possible that our understanding of true incidence is wrong and this is the actual incidence. What I would like them to do, and I think they’re trying to do, is to look at this finding [and compare it with] other more mature databases and other regional databases. One of the current challenges of All of Us is that our patients are basically being recruited from some parts of the country, and the middle of the country has hardly any presence in the database, so it becomes really challenging to understand it,” Dr. Muppidi said in an interview.

However, Dr. Muppidi, who is a clinical professor of neurology at Stanford (Calif.) Medicine, noted that the All of Us database is still growing. When it has recruited more patients with a diverse population, “it [will be a] valuable source for rare diseases to try to understand true incidence of those diseases,” he said.
 

Understanding the true prevalence

Dr. Roy recognized the geographic limitations of the database. “Some states, particularly Massachusetts, New York, and California, had a lot of patients in the database, where there were no patients from many states,” said Dr. Roy, associate professor of neurology at Yale University, New Haven, Conn.

He said that the group is working with other databases, including UK Biobank. “The goal is to incorporate all of these databases together [to determine the true incidence],” said Dr. Roy.

It’s critical to understand the true prevalence of myasthenia gravis since new therapies are in development and coming to market. “I worry that myasthenia gravis might be considered less common than it truly is, and that will limit growth of the field if the feeling is that there are not that many [myasthenia gravis patients] in the country,” said Dr. Muppidi.

The study included data from 369,297 adult patients, using Systematized Nomenclature of Medicine (SNOMED) and International Classification of Diseases (ICD) codes to identify patients with myasthenia gravis. There were 479 cases of myasthenia gravis, for a prevalence of 0.13 (95% confidence interval [CI], 0.12-0.14). Of myasthenia gravis patients, 65% were female and the mean age was 64 years. The prevalence of myasthenia gravis in White individuals was 0.16 (95% CI, 0.15-0.18), of which 63% were female, and the mean age was 66 years. The prevalence among Black individuals was 0.078 (95% CI, 0.060-0.10), with 77% of the population female and a mean age of 58 years. The prevalence in Hispanics was 0.091 (95% CI, 0.070-0.12), with 80% female and a mean age of 58 years. Among Asians, the prevalence was 0.056 (95% CI, 0.025-0.12) and 57% were female, with a mean age of 58 years.

The researchers also looked at the EXPLORE-MG database drawn from Yale (n = 3,269,000), which showed a much lower overall myasthenia gravis prevalence of 0.019 (95% CI, 0.017-0.020), a female proportion of 46.8%, and a mean age of 56.6 years. Notably, EXPLORE-MG had a lower proportion of women and a younger population than All of Us.

The researchers compared data from All of Us with other databases for other conditions. The prevalence of ALS was the same as in other conditions, while diabetic neuropathy was significantly lower (2.7 versus 28.5-50 among diabetic patients) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) was higher (0.084 versus 0.028).

Dr. Muppidi has been on advisory boards for Alexion, Argenx, UBC, and Immunovant. Dr. Roy has consulted for Alexion, Takeda Pharmaceuticals, and Argenx and owns stock in Cabaletta Bio. He has received research support from Takeda, Abcuro, and Argenx.

Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.

But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.

“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.

Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.

“We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures,” Dr. Kaye said.
 

Thank COVID?

Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.

Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.

Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.

RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.

Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.

“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.

“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
 

Hope for Dravet syndrome

Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.

Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.

The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.

“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.

Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.

“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.

“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.

“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
 

A promising future

Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”

And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.

Take, for example, a case reported recently in the New England Journal of Medicine.

Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.

One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.

However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”

“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.

The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.

A version of this article first appeared on Medscape.com.

Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.

But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.

“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.

Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.

“We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures,” Dr. Kaye said.
 

Thank COVID?

Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.

Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.

Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.

RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.

Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.

“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.

“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
 

Hope for Dravet syndrome

Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.

Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.

The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.

“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.

Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.

“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.

“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.

“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
 

A promising future

Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”

And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.

Take, for example, a case reported recently in the New England Journal of Medicine.

Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.

One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.

However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”

“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.

The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.

A version of this article first appeared on Medscape.com.

Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.

But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.

“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.

Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.

“We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures,” Dr. Kaye said.
 

Thank COVID?

Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.

Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.

Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.

RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.

Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.

“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.

“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
 

Hope for Dravet syndrome

Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.

Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.

The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.

“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.

Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.

“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.

“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.

“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
 

A promising future

Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”

And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.

Take, for example, a case reported recently in the New England Journal of Medicine.

Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.

One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.

However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”

“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.

The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.

A version of this article first appeared on Medscape.com.

Cognitive issues in children with Duchenne muscular dystrophy (DMD) are linked to worse outcomes, but limited access to specialists and limited resources make this problem difficult to address. A new tool from the National Institutes of Health, called NIH Toolbox, could improve that outcome, according to Mathula Thangarajh, MD, PhD, who has conducted research in the field.

“When we talk to families and parents, they are able to identify that even during infancy that [children with DMD] have delayed cognitive function. This includes speech delay, but also language and adaptive skills. We also know that those children with speech delay, which is really a very commonly reported phenotype in up to 50%, go on to have school-based needs. They may repeat [grades] in elementary years, but they also use more resources at school,” said Dr. Thangarajh, who is an assistant professor of neurology at the Children’s Hospital of Richmond at Virginia Commonwealth University, Richmond, during a talk at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

Children’s Hospital of Richmond at Virginia Commonwealth University

A previous natural history study that utilized the Pediatric Quality of Life assessment also showed that DMD patients reported the lowest scores in brain health, including emotional health and school performance.

Other research has shown a correlation between cognitive function and survival in DMD. “This suggests that health maintenance may play an important role [in outcomes],” said Dr. Thangarajh. Another study found a correlation between psychomotor delay that required school-based interventions and earlier loss of ambulation, lower cardiac ejection fraction, and worse pulmonary function. The researchers also found that boys with cognitive delay were diagnosed at an earlier age, and yet had delays in diagnosis and worse motor function, pulmonary health, and cardiac health outcomes. On average, they lost ambulatory ability 2 years earlier.

A study by Dr. Thangarajh’s group showed that patients with speech delay and lower IQ had lower performance in timed tests, including 6-minute walk test distance and scored an average of 2 points lower on the North Star Ambulatory Assessment.
 

A tool for continuous cognitive assessment

The Centers for Disease Control and Prevention–supported DMD CARE guidelines only say that neuropsychological evaluations should be considered at diagnosis, but is essential if concerns arise about developmental progress. However, the Muscular Dystrophy Association has found barriers both in access to specialists, with an average wait time of 1-2 years, and burdensome out-of-pocket costs.

Those issues prompted Dr. Thangarajh to look for an alternative solution. At the time that she embarked on this work, the NIH was interested in technologies to assess neurobehavioral issues across different diseases. The resulting NIH Toolbox iPad app was driven largely by failed clinical trials in dementia, and the aim was to be able to provide continuous assessment over time. “It will allow for assessments across the lifespan, so you can use the same construct from age 3 to 80-plus,” said Dr. Thangarajh. It can also normalize population factors, such as annual household income and mother’s IQ.

She set out to validate the NIH Toolbox in children with DMD. The toolbox includes measures of crystalized cognition and fluid cognition. The former encompasses vocabulary and reading ability, which are strongly predicted by socioeconomic status and maternal IQ. On the other hand, fluid cognition includes cognitive features that develop across the lifespan and is directly related to academic underperformance in DMD patients.

Dr. Thangarajh’s group assessed 30 boys with DMD and found that crystallized cognition was normal, but they had a deficit in fluid cognition. They found deficits within several subdomains of fluid cognition. “This tells us that the NIH Toolbox was able to replicate what we had known in the literature, that these boys really have lower intellectual capacity, but they also have significant weakness in fluid cognition,” she said.

She also wanted to examine changes over time by testing the boys at a 1-year interview. “What we found was that they are not making as much gain in fluid cognition as we would like. They are just making marginal improvements over time. This has implications on how often we should screen them, but also not be over reliant on using school-based resources for them to get tested,” said Dr. Thangarajh.

Her group’s analysis of a dataset of 55 boys provided by PTC Therapeutics revealed a difference by age in a test of working memory. “What we found was that boys who are actually greater than 9 years, compared with those who are less than 9 years, they actually had a reversal of development-based improvement. The older they get, they were not making as much gains as you would expect,” said Dr. Thangarajh.

She went on to discuss psychosocial determinants of cognitive health in DMD. It is known that women who are carriers of the dystrophin mutation can underperform in cognitively stressful tasks, leading her to wonder if this could lead to transgenerational risk to offspring with DMD. Her group tested women who were carriers of the mutation with the NIH Toolbox and found that they had lower fluid cognition than noncarriers. They then tested 65 dyads of mothers and children, and found a correlation, but only when it came to inhibitory control, which required the individual to note the direction of an arrow while ignoring surrounding arrows pointing in various directions.

Next, the researchers examined neighborhoods and their impact on cognitive health, which can be affected by the presence of green spaces, access to public transportation and good nutrition, and other factors. There were significant deficits associated with residence zip codes. “We were pretty shocked. Someone who is not in a socially vulnerable region is scoring slightly below average, but someone who is in a very socially vulnerable neighborhood is only scoring 75 [age-adjusted score] on the NIH toolbox. So with this, we can conclude that carrier women are vulnerable in certain cognitive domains, but also children who come from socially vulnerable [situations] have poor cognitive control. This, again, has implications on how often we should screen and how much we should overly rely on school-based resources for these individuals,” said Dr. Thangarajh.
 

Overcoming a significant barrier

The NIH Toolbox has a lot of potential to improve DMD care, according to Dianna Quan, MD, who is the incoming president of AANEM, and professor of neurology at the University of Colorado at Denver, Aurora. “There’s this huge problem in terms of getting people in to see neuropsychologists and having formal evaluations. I think that’s a huge barrier. If we have people able to access this toolkit, which is simple and easily and universally accessible, how wonderful is that? I think that will be a really great improvement on what’s going on right now. It allows people to easily screen for these cognitive disabilities and make sure that we address them,” Dr. Quan said in an interview.

Asked how the tool could specifically improve care, Dr. Quan suggested that the first step is to understand the contributing factors to cognitive issues, whether they are biological, social, or a combination. “Some of them we can modify, potentially, through addressing the social environment. Some of those biologic factors may also be modifiable with many of the new drug studies that are coming.”

Dr. Thangarajh has received speaker honoraria from NS Pharma and PTC Therapeutics. Dr. Quan has received funding from Alnylam, Pfizer, Cytokinetics, Momenta, and Argenx.

Cognitive issues in children with Duchenne muscular dystrophy (DMD) are linked to worse outcomes, but limited access to specialists and limited resources make this problem difficult to address. A new tool from the National Institutes of Health, called NIH Toolbox, could improve that outcome, according to Mathula Thangarajh, MD, PhD, who has conducted research in the field.

“When we talk to families and parents, they are able to identify that even during infancy that [children with DMD] have delayed cognitive function. This includes speech delay, but also language and adaptive skills. We also know that those children with speech delay, which is really a very commonly reported phenotype in up to 50%, go on to have school-based needs. They may repeat [grades] in elementary years, but they also use more resources at school,” said Dr. Thangarajh, who is an assistant professor of neurology at the Children’s Hospital of Richmond at Virginia Commonwealth University, Richmond, during a talk at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

Children’s Hospital of Richmond at Virginia Commonwealth University

A previous natural history study that utilized the Pediatric Quality of Life assessment also showed that DMD patients reported the lowest scores in brain health, including emotional health and school performance.

Other research has shown a correlation between cognitive function and survival in DMD. “This suggests that health maintenance may play an important role [in outcomes],” said Dr. Thangarajh. Another study found a correlation between psychomotor delay that required school-based interventions and earlier loss of ambulation, lower cardiac ejection fraction, and worse pulmonary function. The researchers also found that boys with cognitive delay were diagnosed at an earlier age, and yet had delays in diagnosis and worse motor function, pulmonary health, and cardiac health outcomes. On average, they lost ambulatory ability 2 years earlier.

A study by Dr. Thangarajh’s group showed that patients with speech delay and lower IQ had lower performance in timed tests, including 6-minute walk test distance and scored an average of 2 points lower on the North Star Ambulatory Assessment.
 

A tool for continuous cognitive assessment

The Centers for Disease Control and Prevention–supported DMD CARE guidelines only say that neuropsychological evaluations should be considered at diagnosis, but is essential if concerns arise about developmental progress. However, the Muscular Dystrophy Association has found barriers both in access to specialists, with an average wait time of 1-2 years, and burdensome out-of-pocket costs.

Those issues prompted Dr. Thangarajh to look for an alternative solution. At the time that she embarked on this work, the NIH was interested in technologies to assess neurobehavioral issues across different diseases. The resulting NIH Toolbox iPad app was driven largely by failed clinical trials in dementia, and the aim was to be able to provide continuous assessment over time. “It will allow for assessments across the lifespan, so you can use the same construct from age 3 to 80-plus,” said Dr. Thangarajh. It can also normalize population factors, such as annual household income and mother’s IQ.

She set out to validate the NIH Toolbox in children with DMD. The toolbox includes measures of crystalized cognition and fluid cognition. The former encompasses vocabulary and reading ability, which are strongly predicted by socioeconomic status and maternal IQ. On the other hand, fluid cognition includes cognitive features that develop across the lifespan and is directly related to academic underperformance in DMD patients.

Dr. Thangarajh’s group assessed 30 boys with DMD and found that crystallized cognition was normal, but they had a deficit in fluid cognition. They found deficits within several subdomains of fluid cognition. “This tells us that the NIH Toolbox was able to replicate what we had known in the literature, that these boys really have lower intellectual capacity, but they also have significant weakness in fluid cognition,” she said.

She also wanted to examine changes over time by testing the boys at a 1-year interview. “What we found was that they are not making as much gain in fluid cognition as we would like. They are just making marginal improvements over time. This has implications on how often we should screen them, but also not be over reliant on using school-based resources for them to get tested,” said Dr. Thangarajh.

Her group’s analysis of a dataset of 55 boys provided by PTC Therapeutics revealed a difference by age in a test of working memory. “What we found was that boys who are actually greater than 9 years, compared with those who are less than 9 years, they actually had a reversal of development-based improvement. The older they get, they were not making as much gains as you would expect,” said Dr. Thangarajh.

She went on to discuss psychosocial determinants of cognitive health in DMD. It is known that women who are carriers of the dystrophin mutation can underperform in cognitively stressful tasks, leading her to wonder if this could lead to transgenerational risk to offspring with DMD. Her group tested women who were carriers of the mutation with the NIH Toolbox and found that they had lower fluid cognition than noncarriers. They then tested 65 dyads of mothers and children, and found a correlation, but only when it came to inhibitory control, which required the individual to note the direction of an arrow while ignoring surrounding arrows pointing in various directions.

Next, the researchers examined neighborhoods and their impact on cognitive health, which can be affected by the presence of green spaces, access to public transportation and good nutrition, and other factors. There were significant deficits associated with residence zip codes. “We were pretty shocked. Someone who is not in a socially vulnerable region is scoring slightly below average, but someone who is in a very socially vulnerable neighborhood is only scoring 75 [age-adjusted score] on the NIH toolbox. So with this, we can conclude that carrier women are vulnerable in certain cognitive domains, but also children who come from socially vulnerable [situations] have poor cognitive control. This, again, has implications on how often we should screen and how much we should overly rely on school-based resources for these individuals,” said Dr. Thangarajh.
 

Overcoming a significant barrier

The NIH Toolbox has a lot of potential to improve DMD care, according to Dianna Quan, MD, who is the incoming president of AANEM, and professor of neurology at the University of Colorado at Denver, Aurora. “There’s this huge problem in terms of getting people in to see neuropsychologists and having formal evaluations. I think that’s a huge barrier. If we have people able to access this toolkit, which is simple and easily and universally accessible, how wonderful is that? I think that will be a really great improvement on what’s going on right now. It allows people to easily screen for these cognitive disabilities and make sure that we address them,” Dr. Quan said in an interview.

Asked how the tool could specifically improve care, Dr. Quan suggested that the first step is to understand the contributing factors to cognitive issues, whether they are biological, social, or a combination. “Some of them we can modify, potentially, through addressing the social environment. Some of those biologic factors may also be modifiable with many of the new drug studies that are coming.”

Dr. Thangarajh has received speaker honoraria from NS Pharma and PTC Therapeutics. Dr. Quan has received funding from Alnylam, Pfizer, Cytokinetics, Momenta, and Argenx.

Cognitive issues in children with Duchenne muscular dystrophy (DMD) are linked to worse outcomes, but limited access to specialists and limited resources make this problem difficult to address. A new tool from the National Institutes of Health, called NIH Toolbox, could improve that outcome, according to Mathula Thangarajh, MD, PhD, who has conducted research in the field.

“When we talk to families and parents, they are able to identify that even during infancy that [children with DMD] have delayed cognitive function. This includes speech delay, but also language and adaptive skills. We also know that those children with speech delay, which is really a very commonly reported phenotype in up to 50%, go on to have school-based needs. They may repeat [grades] in elementary years, but they also use more resources at school,” said Dr. Thangarajh, who is an assistant professor of neurology at the Children’s Hospital of Richmond at Virginia Commonwealth University, Richmond, during a talk at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).

Children’s Hospital of Richmond at Virginia Commonwealth University

A previous natural history study that utilized the Pediatric Quality of Life assessment also showed that DMD patients reported the lowest scores in brain health, including emotional health and school performance.

Other research has shown a correlation between cognitive function and survival in DMD. “This suggests that health maintenance may play an important role [in outcomes],” said Dr. Thangarajh. Another study found a correlation between psychomotor delay that required school-based interventions and earlier loss of ambulation, lower cardiac ejection fraction, and worse pulmonary function. The researchers also found that boys with cognitive delay were diagnosed at an earlier age, and yet had delays in diagnosis and worse motor function, pulmonary health, and cardiac health outcomes. On average, they lost ambulatory ability 2 years earlier.

A study by Dr. Thangarajh’s group showed that patients with speech delay and lower IQ had lower performance in timed tests, including 6-minute walk test distance and scored an average of 2 points lower on the North Star Ambulatory Assessment.
 

A tool for continuous cognitive assessment

The Centers for Disease Control and Prevention–supported DMD CARE guidelines only say that neuropsychological evaluations should be considered at diagnosis, but is essential if concerns arise about developmental progress. However, the Muscular Dystrophy Association has found barriers both in access to specialists, with an average wait time of 1-2 years, and burdensome out-of-pocket costs.

Those issues prompted Dr. Thangarajh to look for an alternative solution. At the time that she embarked on this work, the NIH was interested in technologies to assess neurobehavioral issues across different diseases. The resulting NIH Toolbox iPad app was driven largely by failed clinical trials in dementia, and the aim was to be able to provide continuous assessment over time. “It will allow for assessments across the lifespan, so you can use the same construct from age 3 to 80-plus,” said Dr. Thangarajh. It can also normalize population factors, such as annual household income and mother’s IQ.

She set out to validate the NIH Toolbox in children with DMD. The toolbox includes measures of crystalized cognition and fluid cognition. The former encompasses vocabulary and reading ability, which are strongly predicted by socioeconomic status and maternal IQ. On the other hand, fluid cognition includes cognitive features that develop across the lifespan and is directly related to academic underperformance in DMD patients.

Dr. Thangarajh’s group assessed 30 boys with DMD and found that crystallized cognition was normal, but they had a deficit in fluid cognition. They found deficits within several subdomains of fluid cognition. “This tells us that the NIH Toolbox was able to replicate what we had known in the literature, that these boys really have lower intellectual capacity, but they also have significant weakness in fluid cognition,” she said.

She also wanted to examine changes over time by testing the boys at a 1-year interview. “What we found was that they are not making as much gain in fluid cognition as we would like. They are just making marginal improvements over time. This has implications on how often we should screen them, but also not be over reliant on using school-based resources for them to get tested,” said Dr. Thangarajh.

Her group’s analysis of a dataset of 55 boys provided by PTC Therapeutics revealed a difference by age in a test of working memory. “What we found was that boys who are actually greater than 9 years, compared with those who are less than 9 years, they actually had a reversal of development-based improvement. The older they get, they were not making as much gains as you would expect,” said Dr. Thangarajh.

She went on to discuss psychosocial determinants of cognitive health in DMD. It is known that women who are carriers of the dystrophin mutation can underperform in cognitively stressful tasks, leading her to wonder if this could lead to transgenerational risk to offspring with DMD. Her group tested women who were carriers of the mutation with the NIH Toolbox and found that they had lower fluid cognition than noncarriers. They then tested 65 dyads of mothers and children, and found a correlation, but only when it came to inhibitory control, which required the individual to note the direction of an arrow while ignoring surrounding arrows pointing in various directions.

Next, the researchers examined neighborhoods and their impact on cognitive health, which can be affected by the presence of green spaces, access to public transportation and good nutrition, and other factors. There were significant deficits associated with residence zip codes. “We were pretty shocked. Someone who is not in a socially vulnerable region is scoring slightly below average, but someone who is in a very socially vulnerable neighborhood is only scoring 75 [age-adjusted score] on the NIH toolbox. So with this, we can conclude that carrier women are vulnerable in certain cognitive domains, but also children who come from socially vulnerable [situations] have poor cognitive control. This, again, has implications on how often we should screen and how much we should overly rely on school-based resources for these individuals,” said Dr. Thangarajh.
 

Overcoming a significant barrier

The NIH Toolbox has a lot of potential to improve DMD care, according to Dianna Quan, MD, who is the incoming president of AANEM, and professor of neurology at the University of Colorado at Denver, Aurora. “There’s this huge problem in terms of getting people in to see neuropsychologists and having formal evaluations. I think that’s a huge barrier. If we have people able to access this toolkit, which is simple and easily and universally accessible, how wonderful is that? I think that will be a really great improvement on what’s going on right now. It allows people to easily screen for these cognitive disabilities and make sure that we address them,” Dr. Quan said in an interview.

Asked how the tool could specifically improve care, Dr. Quan suggested that the first step is to understand the contributing factors to cognitive issues, whether they are biological, social, or a combination. “Some of them we can modify, potentially, through addressing the social environment. Some of those biologic factors may also be modifiable with many of the new drug studies that are coming.”

Dr. Thangarajh has received speaker honoraria from NS Pharma and PTC Therapeutics. Dr. Quan has received funding from Alnylam, Pfizer, Cytokinetics, Momenta, and Argenx.

PHOENIX – Subcutaneous efgartigimod PH20 SC shows efficacy and tolerability in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), providing a convenient alternative to intravenous and other older treatments for this rare disease.

“This was the largest study of CIDP that has been performed, with over 600 patients screened and 322 enrolled, and was the first to use an adjudication committee to confirm the diagnosis,” said study investigator Richard Lewis, MD, of the department of neurology, Cedars-Sinai Medical Center, Los Angeles.

Furthermore, “this is the first new treatment for CIDP in over 30 years, so it’s very exciting. It is a brief subcutaneous injection, which should be something that patients will appreciate,” he said.

The study was presented at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
 

Filling an unmet need

A rare and often-debilitating autoimmune disorder, CIDP is characterized by weakness and numbness that can result in disability, pain, and fatigue and has been linked to IgG autoantibodies.

Treatments include corticosteroids, intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin, and plasma exchange, but not all patients achieve meaningful benefits and many patients complain about safety risks, costs, and burdensome treatment regimens.

“There is an unmet need for a first-line treatment with long-term efficacy that maintains or improves quality of life, has an early onset of action, is well tolerated, is not dependent on plasma donation, and has greater convenience,” the investigators wrote in their abstract.

Efgartigimod, which is approved in its intravenous and subcutaneous forms for the treatment of myasthenia gravis, is a human IgG1 antibody Fc receptor blocker designed to reduce pathogenic IgG autoantibody levels, which may be drivers of pathogenesis in CIDP.

The therapy is a coformulation of efgartigimod and recombinant human hyaluronidase that allows for rapid subcutaneous administration of larger volumes and is administered as a 90-second subcutaneous injection once weekly.

For the ongoing phase 2 ADHERE trial, 322 patients with a diagnosis of CIDP and active disease who were either treatment naive or receiving standard treatments were withdrawn from their treatments prior to day 1 of a run-in period of up to 12 weeks.

They then entered stage A of the study, an open-label phase in which all were treated with 1,000-mg efgartigimod PH20 SC weekly for up to 12 weeks.

Of those patients, 66% showed evidence of clinical improvement and a rapid onset of effect with the efgartigimod PH20 SC treatment, and 70% of the patients were then entered into stage B, a double-blind randomized phase, with 111 of patients receiving continued efgartigimod PH20 SC weekly and 110 receiving placebo for 48 weeks.

Of those moving on to stage B, more than 70% were on IVIg prior to the time of enrollment.

The study met its primary endpoint, with the efgartigimod PH20 SC groups showing a 61% lower risk for relapse on the basis of time to a first adjusted Inflammatory Neuropathy Cause and Treatment deterioration, compared with placebo (hazard ratio, 0.39; P = .000039).

Clinical benefits were also observed on the Inflammatory Rasch-built Overall Disability Scale (I-RODS) and in measures of mean grip strength in all groups regardless of prior CIDP medication.

Specifically, efgartigimod patients had a mean improvement of 7.7 points on I-RODS and 12.3 kPa on mean grip strength in stage A, which was maintained in stage B. These were partially lost in patients receiving placebo.

In terms of safety, most adverse events were mild or moderate in severity, and no new safety signals were identified with up to 60 weeks of treatment. There were no increased infection rates with increased exposure.

The findings show that “efgartigimod-PH20, given as a 90-second subcutaneous injection once a week, was effective in treating patients with CIDP who had relapsed when taken off their previous treatment (IVIg or corticosteroids),” said Dr. Lewis.

“[The study] then showed that the majority of patients, over 70%, maintained that improvement, compared with placebo, where over 50% relapsed – most within 8 weeks, so the treatment, which reduces circulating immunoglobulin G by over 70%, is effective in treating CIDP,” he added.

Plans for this ongoing trial include recruiting up to 360 patients until 88 events of clinical deterioration have been observed in stage B.
 

Promising data

Commenting on the study, Karissa Gable, MD, an associate professor of neurology at Duke University, Durham, N.C., said that the “initial data reported from the ADHERE study is very promising and demonstrated significant efficacy.”

The study’s use of an adjudication committee in confirming the diagnosis is particularly notable, she said. “The trial design demonstrated confirmation of diagnosis and activity of disease and response to drug prior to randomization, which is a novel design that is particularly applicable to patients with CIDP given the rate of misdiagnosis and placebo effect found in other trials.”

Dr. Gable agreed that new options are important to address an unmet need in CIDP.

“The current first-line treatments are generally 80%-90% effective, however, there are limited options with respect to the first line treatments due to side effects and comorbid disease in patients,” she explained.

“Other treatments options are needed and so this is an unmet need in patients with CIDP,” Dr. Gable said. “This medication will be likely to be one that will provide a strong alternate option for treatment.”

Overall, “this is a novel mechanism for drug treatment for CIDP and seems to demonstrate efficacy and good safety and tolerability based on the initial report of the data,” Dr. Gable added.

“It will likely be a promising medication to use for these patients to fill the unmet need for treatment of patients with CIDP.”

The study was sponsored by Argenx. Dr. Lewis disclosed relationships with Argenx and other companies involved in neuromuscular disease therapies. Dr. Gable is on the global medical advisory board steering committee for Argenx and she was the principal investigator at her site for the Adhere study. Dr. Gable has served as a consultant for Immunovant and Takeda as well as Sanofi for CIDP and she is on the Takeda speaker bureau for Huyquvia for treatment of CIDP.

A version of this article first appeared on Medscape.com.

PHOENIX – Subcutaneous efgartigimod PH20 SC shows efficacy and tolerability in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), providing a convenient alternative to intravenous and other older treatments for this rare disease.

“This was the largest study of CIDP that has been performed, with over 600 patients screened and 322 enrolled, and was the first to use an adjudication committee to confirm the diagnosis,” said study investigator Richard Lewis, MD, of the department of neurology, Cedars-Sinai Medical Center, Los Angeles.

Furthermore, “this is the first new treatment for CIDP in over 30 years, so it’s very exciting. It is a brief subcutaneous injection, which should be something that patients will appreciate,” he said.

The study was presented at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
 

Filling an unmet need

A rare and often-debilitating autoimmune disorder, CIDP is characterized by weakness and numbness that can result in disability, pain, and fatigue and has been linked to IgG autoantibodies.

Treatments include corticosteroids, intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin, and plasma exchange, but not all patients achieve meaningful benefits and many patients complain about safety risks, costs, and burdensome treatment regimens.

“There is an unmet need for a first-line treatment with long-term efficacy that maintains or improves quality of life, has an early onset of action, is well tolerated, is not dependent on plasma donation, and has greater convenience,” the investigators wrote in their abstract.

Efgartigimod, which is approved in its intravenous and subcutaneous forms for the treatment of myasthenia gravis, is a human IgG1 antibody Fc receptor blocker designed to reduce pathogenic IgG autoantibody levels, which may be drivers of pathogenesis in CIDP.

The therapy is a coformulation of efgartigimod and recombinant human hyaluronidase that allows for rapid subcutaneous administration of larger volumes and is administered as a 90-second subcutaneous injection once weekly.

For the ongoing phase 2 ADHERE trial, 322 patients with a diagnosis of CIDP and active disease who were either treatment naive or receiving standard treatments were withdrawn from their treatments prior to day 1 of a run-in period of up to 12 weeks.

They then entered stage A of the study, an open-label phase in which all were treated with 1,000-mg efgartigimod PH20 SC weekly for up to 12 weeks.

Of those patients, 66% showed evidence of clinical improvement and a rapid onset of effect with the efgartigimod PH20 SC treatment, and 70% of the patients were then entered into stage B, a double-blind randomized phase, with 111 of patients receiving continued efgartigimod PH20 SC weekly and 110 receiving placebo for 48 weeks.

Of those moving on to stage B, more than 70% were on IVIg prior to the time of enrollment.

The study met its primary endpoint, with the efgartigimod PH20 SC groups showing a 61% lower risk for relapse on the basis of time to a first adjusted Inflammatory Neuropathy Cause and Treatment deterioration, compared with placebo (hazard ratio, 0.39; P = .000039).

Clinical benefits were also observed on the Inflammatory Rasch-built Overall Disability Scale (I-RODS) and in measures of mean grip strength in all groups regardless of prior CIDP medication.

Specifically, efgartigimod patients had a mean improvement of 7.7 points on I-RODS and 12.3 kPa on mean grip strength in stage A, which was maintained in stage B. These were partially lost in patients receiving placebo.

In terms of safety, most adverse events were mild or moderate in severity, and no new safety signals were identified with up to 60 weeks of treatment. There were no increased infection rates with increased exposure.

The findings show that “efgartigimod-PH20, given as a 90-second subcutaneous injection once a week, was effective in treating patients with CIDP who had relapsed when taken off their previous treatment (IVIg or corticosteroids),” said Dr. Lewis.

“[The study] then showed that the majority of patients, over 70%, maintained that improvement, compared with placebo, where over 50% relapsed – most within 8 weeks, so the treatment, which reduces circulating immunoglobulin G by over 70%, is effective in treating CIDP,” he added.

Plans for this ongoing trial include recruiting up to 360 patients until 88 events of clinical deterioration have been observed in stage B.
 

Promising data

Commenting on the study, Karissa Gable, MD, an associate professor of neurology at Duke University, Durham, N.C., said that the “initial data reported from the ADHERE study is very promising and demonstrated significant efficacy.”

The study’s use of an adjudication committee in confirming the diagnosis is particularly notable, she said. “The trial design demonstrated confirmation of diagnosis and activity of disease and response to drug prior to randomization, which is a novel design that is particularly applicable to patients with CIDP given the rate of misdiagnosis and placebo effect found in other trials.”

Dr. Gable agreed that new options are important to address an unmet need in CIDP.

“The current first-line treatments are generally 80%-90% effective, however, there are limited options with respect to the first line treatments due to side effects and comorbid disease in patients,” she explained.

“Other treatments options are needed and so this is an unmet need in patients with CIDP,” Dr. Gable said. “This medication will be likely to be one that will provide a strong alternate option for treatment.”

Overall, “this is a novel mechanism for drug treatment for CIDP and seems to demonstrate efficacy and good safety and tolerability based on the initial report of the data,” Dr. Gable added.

“It will likely be a promising medication to use for these patients to fill the unmet need for treatment of patients with CIDP.”

The study was sponsored by Argenx. Dr. Lewis disclosed relationships with Argenx and other companies involved in neuromuscular disease therapies. Dr. Gable is on the global medical advisory board steering committee for Argenx and she was the principal investigator at her site for the Adhere study. Dr. Gable has served as a consultant for Immunovant and Takeda as well as Sanofi for CIDP and she is on the Takeda speaker bureau for Huyquvia for treatment of CIDP.

A version of this article first appeared on Medscape.com.

PHOENIX – Subcutaneous efgartigimod PH20 SC shows efficacy and tolerability in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), providing a convenient alternative to intravenous and other older treatments for this rare disease.

“This was the largest study of CIDP that has been performed, with over 600 patients screened and 322 enrolled, and was the first to use an adjudication committee to confirm the diagnosis,” said study investigator Richard Lewis, MD, of the department of neurology, Cedars-Sinai Medical Center, Los Angeles.

Furthermore, “this is the first new treatment for CIDP in over 30 years, so it’s very exciting. It is a brief subcutaneous injection, which should be something that patients will appreciate,” he said.

The study was presented at the 2023 annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine (AANEM).
 

Filling an unmet need

A rare and often-debilitating autoimmune disorder, CIDP is characterized by weakness and numbness that can result in disability, pain, and fatigue and has been linked to IgG autoantibodies.

Treatments include corticosteroids, intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin, and plasma exchange, but not all patients achieve meaningful benefits and many patients complain about safety risks, costs, and burdensome treatment regimens.

“There is an unmet need for a first-line treatment with long-term efficacy that maintains or improves quality of life, has an early onset of action, is well tolerated, is not dependent on plasma donation, and has greater convenience,” the investigators wrote in their abstract.

Efgartigimod, which is approved in its intravenous and subcutaneous forms for the treatment of myasthenia gravis, is a human IgG1 antibody Fc receptor blocker designed to reduce pathogenic IgG autoantibody levels, which may be drivers of pathogenesis in CIDP.

The therapy is a coformulation of efgartigimod and recombinant human hyaluronidase that allows for rapid subcutaneous administration of larger volumes and is administered as a 90-second subcutaneous injection once weekly.

For the ongoing phase 2 ADHERE trial, 322 patients with a diagnosis of CIDP and active disease who were either treatment naive or receiving standard treatments were withdrawn from their treatments prior to day 1 of a run-in period of up to 12 weeks.

They then entered stage A of the study, an open-label phase in which all were treated with 1,000-mg efgartigimod PH20 SC weekly for up to 12 weeks.

Of those patients, 66% showed evidence of clinical improvement and a rapid onset of effect with the efgartigimod PH20 SC treatment, and 70% of the patients were then entered into stage B, a double-blind randomized phase, with 111 of patients receiving continued efgartigimod PH20 SC weekly and 110 receiving placebo for 48 weeks.

Of those moving on to stage B, more than 70% were on IVIg prior to the time of enrollment.

The study met its primary endpoint, with the efgartigimod PH20 SC groups showing a 61% lower risk for relapse on the basis of time to a first adjusted Inflammatory Neuropathy Cause and Treatment deterioration, compared with placebo (hazard ratio, 0.39; P = .000039).

Clinical benefits were also observed on the Inflammatory Rasch-built Overall Disability Scale (I-RODS) and in measures of mean grip strength in all groups regardless of prior CIDP medication.

Specifically, efgartigimod patients had a mean improvement of 7.7 points on I-RODS and 12.3 kPa on mean grip strength in stage A, which was maintained in stage B. These were partially lost in patients receiving placebo.

In terms of safety, most adverse events were mild or moderate in severity, and no new safety signals were identified with up to 60 weeks of treatment. There were no increased infection rates with increased exposure.

The findings show that “efgartigimod-PH20, given as a 90-second subcutaneous injection once a week, was effective in treating patients with CIDP who had relapsed when taken off their previous treatment (IVIg or corticosteroids),” said Dr. Lewis.

“[The study] then showed that the majority of patients, over 70%, maintained that improvement, compared with placebo, where over 50% relapsed – most within 8 weeks, so the treatment, which reduces circulating immunoglobulin G by over 70%, is effective in treating CIDP,” he added.

Plans for this ongoing trial include recruiting up to 360 patients until 88 events of clinical deterioration have been observed in stage B.
 

Promising data

Commenting on the study, Karissa Gable, MD, an associate professor of neurology at Duke University, Durham, N.C., said that the “initial data reported from the ADHERE study is very promising and demonstrated significant efficacy.”

The study’s use of an adjudication committee in confirming the diagnosis is particularly notable, she said. “The trial design demonstrated confirmation of diagnosis and activity of disease and response to drug prior to randomization, which is a novel design that is particularly applicable to patients with CIDP given the rate of misdiagnosis and placebo effect found in other trials.”

Dr. Gable agreed that new options are important to address an unmet need in CIDP.

“The current first-line treatments are generally 80%-90% effective, however, there are limited options with respect to the first line treatments due to side effects and comorbid disease in patients,” she explained.

“Other treatments options are needed and so this is an unmet need in patients with CIDP,” Dr. Gable said. “This medication will be likely to be one that will provide a strong alternate option for treatment.”

Overall, “this is a novel mechanism for drug treatment for CIDP and seems to demonstrate efficacy and good safety and tolerability based on the initial report of the data,” Dr. Gable added.

“It will likely be a promising medication to use for these patients to fill the unmet need for treatment of patients with CIDP.”

The study was sponsored by Argenx. Dr. Lewis disclosed relationships with Argenx and other companies involved in neuromuscular disease therapies. Dr. Gable is on the global medical advisory board steering committee for Argenx and she was the principal investigator at her site for the Adhere study. Dr. Gable has served as a consultant for Immunovant and Takeda as well as Sanofi for CIDP and she is on the Takeda speaker bureau for Huyquvia for treatment of CIDP.

A version of this article first appeared on Medscape.com.