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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Risk of stent infection low, but may be underreported
Infections of coronary stents appear to be uncommon, but it is not clear if they are often missed, underreported, or truly rare, according to a new analysis.
In a search of multiple databases, 79 cases of coronary stent infections (CSI) were found in 65 published reports, according to Venkatakrishnan Ramakumar, MBBS, MD, department of cardiology, All India Institute of Medical Sciences, New Delhi.
Over the period of evaluation, which had no defined starting point but stretched to November 2021, the 79 infections reported worldwide occurred when millions of percutaneous coronary intervention (PCI) procedures were performed. In the United States alone, the current estimated annual number of PCIs is 600,000, according to an article published in the Journal of the American Heart Association.
If the number of reported CSI cases represented even a modest fraction of those that occurred, the risk would still be almost negligible. Yet, Dr. Ramakumar insisted that there has been little attention paid to the potential for CSI, creating a situation in which many or almost all cases are simply being missed.
“We do not know how many infections have gone unrecognized,” Dr. Ramakumar said in presenting his results at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute. And even if they are identified and promptly treated, there “is the potential for a publication bias,” he added, referring to the reluctance of investigators to submit and publishers to accept manuscripts with negative results.
Regardless of the frequency with which they occur, CSI is associated with bad outcomes, according to the data evaluated by Dr. Ramakumar. On the basis of in-hospital mortality, the primary endpoint of this analysis, the rate of death in patients developing CSI was 30.3%.
Successful treatment varied by hospital type
This risk was not uniform. Rather, rates of in-hospital mortality and proportion of patients treated successfully varied substantially by type of hospital. At private teaching hospitals for example, successful treatment – whether medical alone or followed by bailout surgery – was 80%. The rates fell to 40% at public teaching hospitals and then to 25% at private nonteaching hospitals.
The full-text articles included in this analysis were evaluated and selected by two reviewers working independently. A CSI diagnosis made clinically or with imaging and treatment outcomes were among criteria for the case studies to be included. Dr. Ramakumar said the study, which he claimed is the largest systematic review of CSI ever conducted, has been registered with PROSPERO, an international prospective registry of systematic reviews.
The presenting symptom was fever in 72% of cases and chest pain in the others, although there was one asymptomatic CSI reported. On angiography, 62% had a concomitant mycotic aneurysm. Intramyocardial abscess (13.9%), rupture (11.3%), and coronary fistula (7.5%) were also common findings, but no angiographic abnormalities could be identified in 53% of patients.
Following PCI, most CSI developed within 8 days (43%) or the first month (23%), but CSI was reported more than 6 months after the procedure in 19%. Complex PCI accounted for 51% of cases. Of stent types, 56% were drug eluting and 13% were bare metal.
When comparing characteristics of those who survived CSI with those who did not, most (89%) of those with a non–ST-segment elevated acute coronary syndrome ultimately survived, while survival from CSI in those with structural heart disease was only 17%.
Microbiological findings were not a criterion for study inclusion, but Staphylococcus species accounted for 65% of the infections for which positive cultures were reported. Pseudomonas accounted for 13%. Less than 4% (3.8%) tested positive for multiple pathogens. A small proportion of patients had unusual infectious organisms.
As part of this analysis, the investigators developed an artificial intelligence model to predict CSI based on patient characteristics and other variables. However, the specificity of only around 70% led Dr. Ramakumar to conclude that it does not yet have practical value.
However, he believes that better methodology to detect CSI is needed, and he proposed a diagnostic algorithm that he believes would both improve detection rates and accelerate the time to diagnosis.
Algorithm proposed for detection of CSI
In this algorithm, the first step in symptomatic patients with a positive blood culture suspected of CSI is imaging, such as transthoracic echocardiography, to identify features of infective endocarditis or endarteritis. If the imaging is positive, further imaging, such as PET, that supports the diagnosis, should be adequate to support a diagnosis and treatment.
If initial imaging is negative, alternative diagnoses should be considered, but Dr. Ramakumar advised repeat imaging after 48 hours if symptoms persist and no other causes are found.
Dr. Ramakumar acknowledged the many limitations of this analysis, including the small sample size and the challenges of assembling coherent data from case reports with variable types of information submitted during different eras of PCI evolution. However, reiterating that CSI might be frequently missed, he emphasized that this problem might be bigger than currently understood.
It is difficult to rule out any possibility that CSI is frequently missed, but Andrew Sharp, MD, PhD, a consultant interventional cardiologist at the University Hospital of Wales, Cardiff, is skeptical.
“One might think this is a potential problem, but I cannot think of one patient in whom this has occurred,” Dr. Sharp said in an interview. He is fairly confident that they are extremely rare.
“When there is infection associated with a foreign body, such as a pacemaker, they do not typically resolve by themselves,” he explained. “Often the device has to be removed. If this was true for CSI, then I think we would be aware of these complications.”
However, he praised the investigators for taking a look at CSI in a systematic approach. An invited panelist during the CRT featured research, which is where these data were presented, Dr. Sharp was more interested in understanding why they do not occur now that data are available to suggest they are rare.
“Is there something in the coronary environment, such as the consistent blood flow, that protects against infection?” he asked. CSI is a valid area of further research, according to Dr. Sharp, but he does not consider infected stents to be a common threat based on his own sizable case series.
Dr. Ramakumar and Dr. Sharp reported no potential conflicts of interest.
Infections of coronary stents appear to be uncommon, but it is not clear if they are often missed, underreported, or truly rare, according to a new analysis.
In a search of multiple databases, 79 cases of coronary stent infections (CSI) were found in 65 published reports, according to Venkatakrishnan Ramakumar, MBBS, MD, department of cardiology, All India Institute of Medical Sciences, New Delhi.
Over the period of evaluation, which had no defined starting point but stretched to November 2021, the 79 infections reported worldwide occurred when millions of percutaneous coronary intervention (PCI) procedures were performed. In the United States alone, the current estimated annual number of PCIs is 600,000, according to an article published in the Journal of the American Heart Association.
If the number of reported CSI cases represented even a modest fraction of those that occurred, the risk would still be almost negligible. Yet, Dr. Ramakumar insisted that there has been little attention paid to the potential for CSI, creating a situation in which many or almost all cases are simply being missed.
“We do not know how many infections have gone unrecognized,” Dr. Ramakumar said in presenting his results at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute. And even if they are identified and promptly treated, there “is the potential for a publication bias,” he added, referring to the reluctance of investigators to submit and publishers to accept manuscripts with negative results.
Regardless of the frequency with which they occur, CSI is associated with bad outcomes, according to the data evaluated by Dr. Ramakumar. On the basis of in-hospital mortality, the primary endpoint of this analysis, the rate of death in patients developing CSI was 30.3%.
Successful treatment varied by hospital type
This risk was not uniform. Rather, rates of in-hospital mortality and proportion of patients treated successfully varied substantially by type of hospital. At private teaching hospitals for example, successful treatment – whether medical alone or followed by bailout surgery – was 80%. The rates fell to 40% at public teaching hospitals and then to 25% at private nonteaching hospitals.
The full-text articles included in this analysis were evaluated and selected by two reviewers working independently. A CSI diagnosis made clinically or with imaging and treatment outcomes were among criteria for the case studies to be included. Dr. Ramakumar said the study, which he claimed is the largest systematic review of CSI ever conducted, has been registered with PROSPERO, an international prospective registry of systematic reviews.
The presenting symptom was fever in 72% of cases and chest pain in the others, although there was one asymptomatic CSI reported. On angiography, 62% had a concomitant mycotic aneurysm. Intramyocardial abscess (13.9%), rupture (11.3%), and coronary fistula (7.5%) were also common findings, but no angiographic abnormalities could be identified in 53% of patients.
Following PCI, most CSI developed within 8 days (43%) or the first month (23%), but CSI was reported more than 6 months after the procedure in 19%. Complex PCI accounted for 51% of cases. Of stent types, 56% were drug eluting and 13% were bare metal.
When comparing characteristics of those who survived CSI with those who did not, most (89%) of those with a non–ST-segment elevated acute coronary syndrome ultimately survived, while survival from CSI in those with structural heart disease was only 17%.
Microbiological findings were not a criterion for study inclusion, but Staphylococcus species accounted for 65% of the infections for which positive cultures were reported. Pseudomonas accounted for 13%. Less than 4% (3.8%) tested positive for multiple pathogens. A small proportion of patients had unusual infectious organisms.
As part of this analysis, the investigators developed an artificial intelligence model to predict CSI based on patient characteristics and other variables. However, the specificity of only around 70% led Dr. Ramakumar to conclude that it does not yet have practical value.
However, he believes that better methodology to detect CSI is needed, and he proposed a diagnostic algorithm that he believes would both improve detection rates and accelerate the time to diagnosis.
Algorithm proposed for detection of CSI
In this algorithm, the first step in symptomatic patients with a positive blood culture suspected of CSI is imaging, such as transthoracic echocardiography, to identify features of infective endocarditis or endarteritis. If the imaging is positive, further imaging, such as PET, that supports the diagnosis, should be adequate to support a diagnosis and treatment.
If initial imaging is negative, alternative diagnoses should be considered, but Dr. Ramakumar advised repeat imaging after 48 hours if symptoms persist and no other causes are found.
Dr. Ramakumar acknowledged the many limitations of this analysis, including the small sample size and the challenges of assembling coherent data from case reports with variable types of information submitted during different eras of PCI evolution. However, reiterating that CSI might be frequently missed, he emphasized that this problem might be bigger than currently understood.
It is difficult to rule out any possibility that CSI is frequently missed, but Andrew Sharp, MD, PhD, a consultant interventional cardiologist at the University Hospital of Wales, Cardiff, is skeptical.
“One might think this is a potential problem, but I cannot think of one patient in whom this has occurred,” Dr. Sharp said in an interview. He is fairly confident that they are extremely rare.
“When there is infection associated with a foreign body, such as a pacemaker, they do not typically resolve by themselves,” he explained. “Often the device has to be removed. If this was true for CSI, then I think we would be aware of these complications.”
However, he praised the investigators for taking a look at CSI in a systematic approach. An invited panelist during the CRT featured research, which is where these data were presented, Dr. Sharp was more interested in understanding why they do not occur now that data are available to suggest they are rare.
“Is there something in the coronary environment, such as the consistent blood flow, that protects against infection?” he asked. CSI is a valid area of further research, according to Dr. Sharp, but he does not consider infected stents to be a common threat based on his own sizable case series.
Dr. Ramakumar and Dr. Sharp reported no potential conflicts of interest.
Infections of coronary stents appear to be uncommon, but it is not clear if they are often missed, underreported, or truly rare, according to a new analysis.
In a search of multiple databases, 79 cases of coronary stent infections (CSI) were found in 65 published reports, according to Venkatakrishnan Ramakumar, MBBS, MD, department of cardiology, All India Institute of Medical Sciences, New Delhi.
Over the period of evaluation, which had no defined starting point but stretched to November 2021, the 79 infections reported worldwide occurred when millions of percutaneous coronary intervention (PCI) procedures were performed. In the United States alone, the current estimated annual number of PCIs is 600,000, according to an article published in the Journal of the American Heart Association.
If the number of reported CSI cases represented even a modest fraction of those that occurred, the risk would still be almost negligible. Yet, Dr. Ramakumar insisted that there has been little attention paid to the potential for CSI, creating a situation in which many or almost all cases are simply being missed.
“We do not know how many infections have gone unrecognized,” Dr. Ramakumar said in presenting his results at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute. And even if they are identified and promptly treated, there “is the potential for a publication bias,” he added, referring to the reluctance of investigators to submit and publishers to accept manuscripts with negative results.
Regardless of the frequency with which they occur, CSI is associated with bad outcomes, according to the data evaluated by Dr. Ramakumar. On the basis of in-hospital mortality, the primary endpoint of this analysis, the rate of death in patients developing CSI was 30.3%.
Successful treatment varied by hospital type
This risk was not uniform. Rather, rates of in-hospital mortality and proportion of patients treated successfully varied substantially by type of hospital. At private teaching hospitals for example, successful treatment – whether medical alone or followed by bailout surgery – was 80%. The rates fell to 40% at public teaching hospitals and then to 25% at private nonteaching hospitals.
The full-text articles included in this analysis were evaluated and selected by two reviewers working independently. A CSI diagnosis made clinically or with imaging and treatment outcomes were among criteria for the case studies to be included. Dr. Ramakumar said the study, which he claimed is the largest systematic review of CSI ever conducted, has been registered with PROSPERO, an international prospective registry of systematic reviews.
The presenting symptom was fever in 72% of cases and chest pain in the others, although there was one asymptomatic CSI reported. On angiography, 62% had a concomitant mycotic aneurysm. Intramyocardial abscess (13.9%), rupture (11.3%), and coronary fistula (7.5%) were also common findings, but no angiographic abnormalities could be identified in 53% of patients.
Following PCI, most CSI developed within 8 days (43%) or the first month (23%), but CSI was reported more than 6 months after the procedure in 19%. Complex PCI accounted for 51% of cases. Of stent types, 56% were drug eluting and 13% were bare metal.
When comparing characteristics of those who survived CSI with those who did not, most (89%) of those with a non–ST-segment elevated acute coronary syndrome ultimately survived, while survival from CSI in those with structural heart disease was only 17%.
Microbiological findings were not a criterion for study inclusion, but Staphylococcus species accounted for 65% of the infections for which positive cultures were reported. Pseudomonas accounted for 13%. Less than 4% (3.8%) tested positive for multiple pathogens. A small proportion of patients had unusual infectious organisms.
As part of this analysis, the investigators developed an artificial intelligence model to predict CSI based on patient characteristics and other variables. However, the specificity of only around 70% led Dr. Ramakumar to conclude that it does not yet have practical value.
However, he believes that better methodology to detect CSI is needed, and he proposed a diagnostic algorithm that he believes would both improve detection rates and accelerate the time to diagnosis.
Algorithm proposed for detection of CSI
In this algorithm, the first step in symptomatic patients with a positive blood culture suspected of CSI is imaging, such as transthoracic echocardiography, to identify features of infective endocarditis or endarteritis. If the imaging is positive, further imaging, such as PET, that supports the diagnosis, should be adequate to support a diagnosis and treatment.
If initial imaging is negative, alternative diagnoses should be considered, but Dr. Ramakumar advised repeat imaging after 48 hours if symptoms persist and no other causes are found.
Dr. Ramakumar acknowledged the many limitations of this analysis, including the small sample size and the challenges of assembling coherent data from case reports with variable types of information submitted during different eras of PCI evolution. However, reiterating that CSI might be frequently missed, he emphasized that this problem might be bigger than currently understood.
It is difficult to rule out any possibility that CSI is frequently missed, but Andrew Sharp, MD, PhD, a consultant interventional cardiologist at the University Hospital of Wales, Cardiff, is skeptical.
“One might think this is a potential problem, but I cannot think of one patient in whom this has occurred,” Dr. Sharp said in an interview. He is fairly confident that they are extremely rare.
“When there is infection associated with a foreign body, such as a pacemaker, they do not typically resolve by themselves,” he explained. “Often the device has to be removed. If this was true for CSI, then I think we would be aware of these complications.”
However, he praised the investigators for taking a look at CSI in a systematic approach. An invited panelist during the CRT featured research, which is where these data were presented, Dr. Sharp was more interested in understanding why they do not occur now that data are available to suggest they are rare.
“Is there something in the coronary environment, such as the consistent blood flow, that protects against infection?” he asked. CSI is a valid area of further research, according to Dr. Sharp, but he does not consider infected stents to be a common threat based on his own sizable case series.
Dr. Ramakumar and Dr. Sharp reported no potential conflicts of interest.
FROM CRT 2023
A better MS measure?
“When you measure disability, what you really want to know is how things are changing in the patient’s life and not your perception of how they’re changing,” said Mark Gudesblatt, MD, who presented a study comparing the technique, called quantitative gait analysis, to other measures at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The device, called Protokinetics, has been used in clinical studies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, Friederich’s ataxia, and other conditions. The device is a digitized carpet that senses weight change and pressure as the individual walks.
“We can actually measure performance, and the performance is not just how fast you walk 25 feet. We’re measuring things that underlie how you walk: step length, step length variability, velocity, weight shift, how much time you spend on one leg. So it’s like listening to a symphony. We’re not measuring just the trumpets or the violins, we’re measuring everything,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Center at South Shore Neurologic Associates, Patchogue, N.Y.
Commonly used measures include the Expanded Disability Status Scale (EDSS), the 25-foot time walk (25’TW), and the Timed Up and Go (TUG).
Those measures are useful but don’t really measure up to clinical need, Dr. Gudesblatt said. “What you want is no evidence of disease activity, whether that’s multiple dimensions of thinking or multiple dimensions of walking, or changes on an MRI that are not the radiologist’s impression. Patients always say: ‘Doc, I’m worse.’ And we say: ‘Well, your exam is unchanged, your MRI has not changed. But they are worse for reasons – either their perception or their performance. So you can measure this very granularly, and you can relate it to their fear of falling, their balance confidence. This ups the game,” said Dr. Gudesblatt.
“And here’s where it gets even more interesting. You can use this for signatures of disease,” he added. The data can, for example, suggest that instead of Parkinson’s disease, a patient may have a Parkinson’s variant. “What we’re doing is showing how the 25-foot timed walk and Timed Up and Go are very traditional, conservative measures. They’re equivalent to the Pony Express. They’re good, but not where you want to be.”
Technology provides more sensitive, but more complex data
Digital tools to measure a variety of functions, including gait, cognition, and upper limb function are becoming increasingly common in MS, according to Catherine Larochelle, MD, PhD, who was asked for comment. “They are easily providing measures that are likely more sensitive and diverse and probably more meaningful about the daily functional status of a person than our usual EDSS,” said Dr. Larochelle, who is an associate professor at Université de Montréal.
The next step is to determine how best to use the complex data that such devices generate. “Lots of research is being done to better understand how to use the rich but complex data obtained with these tools to provide useful information to people with MS and their clinical team, to help guide shared clinical decisions, and likely accelerate and improve outcomes in clinical trials. So this is a very exciting new era in terms of clinical neurological assessment,” said Dr. Larochelle.
Granular gait analysis
Dr. Gudesblatt and colleagues analyzed retrospective data from 105 people with MS (69% female; average age, 53.7 years). Participants underwent all tests on the same day. The digital gait analysis captured velocity, double support, cadence, functional ambulation profile, gait variability index, and walk ratio over three trials conducted at preferred walking speed (PWS) and during dual task walking.
There were statistically significant relationships (P ≤ .01) between TUG and 25’TW (R2 = 0.62). There were also significant relationships between 25’TW and digital parameters measured at PWS: velocity (R2 = 0.63); double support (R2 = 0.74); cadence (R2 = 0.56); and gait variability index (R2 = 0.54). During dual task walking, there were relationships between 25’TW and velocity (R2 = 0.53); double support (R2 = 0.30); cadence (R2 = 0.43); and gait variability index (R2 = 0.46).
TUG values were significantly associated with gait parameters during PWS: velocity (R2 = 0.71); double support (R2 = 0.75); cadence (R2 = 0.43); gait variability index (R2 = 0.45); and walk ratio (R2 = 0.06). During dual task walking, TUG values were significantly associated with velocity (R2 = 0.55), double support (R2 = 0.21), cadence (R2 = 0.45), and gait variability index (R2 = 0.39).
“With the availability multiple effective disease modifying therapies and the future potential of restorative or reparative treatments, more granular, validated standardized outcome measures are urgently needed,” said Dr. Gudesblatt. Analysis of gait cycle can provide clinically useful information not adequately captured by the current, more traditional approaches of measuring outcomes in MS.
Dr. Gudesblatt and Dr. Larochelle have no relevant financial disclosures.
“When you measure disability, what you really want to know is how things are changing in the patient’s life and not your perception of how they’re changing,” said Mark Gudesblatt, MD, who presented a study comparing the technique, called quantitative gait analysis, to other measures at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The device, called Protokinetics, has been used in clinical studies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, Friederich’s ataxia, and other conditions. The device is a digitized carpet that senses weight change and pressure as the individual walks.
“We can actually measure performance, and the performance is not just how fast you walk 25 feet. We’re measuring things that underlie how you walk: step length, step length variability, velocity, weight shift, how much time you spend on one leg. So it’s like listening to a symphony. We’re not measuring just the trumpets or the violins, we’re measuring everything,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Center at South Shore Neurologic Associates, Patchogue, N.Y.
Commonly used measures include the Expanded Disability Status Scale (EDSS), the 25-foot time walk (25’TW), and the Timed Up and Go (TUG).
Those measures are useful but don’t really measure up to clinical need, Dr. Gudesblatt said. “What you want is no evidence of disease activity, whether that’s multiple dimensions of thinking or multiple dimensions of walking, or changes on an MRI that are not the radiologist’s impression. Patients always say: ‘Doc, I’m worse.’ And we say: ‘Well, your exam is unchanged, your MRI has not changed. But they are worse for reasons – either their perception or their performance. So you can measure this very granularly, and you can relate it to their fear of falling, their balance confidence. This ups the game,” said Dr. Gudesblatt.
“And here’s where it gets even more interesting. You can use this for signatures of disease,” he added. The data can, for example, suggest that instead of Parkinson’s disease, a patient may have a Parkinson’s variant. “What we’re doing is showing how the 25-foot timed walk and Timed Up and Go are very traditional, conservative measures. They’re equivalent to the Pony Express. They’re good, but not where you want to be.”
Technology provides more sensitive, but more complex data
Digital tools to measure a variety of functions, including gait, cognition, and upper limb function are becoming increasingly common in MS, according to Catherine Larochelle, MD, PhD, who was asked for comment. “They are easily providing measures that are likely more sensitive and diverse and probably more meaningful about the daily functional status of a person than our usual EDSS,” said Dr. Larochelle, who is an associate professor at Université de Montréal.
The next step is to determine how best to use the complex data that such devices generate. “Lots of research is being done to better understand how to use the rich but complex data obtained with these tools to provide useful information to people with MS and their clinical team, to help guide shared clinical decisions, and likely accelerate and improve outcomes in clinical trials. So this is a very exciting new era in terms of clinical neurological assessment,” said Dr. Larochelle.
Granular gait analysis
Dr. Gudesblatt and colleagues analyzed retrospective data from 105 people with MS (69% female; average age, 53.7 years). Participants underwent all tests on the same day. The digital gait analysis captured velocity, double support, cadence, functional ambulation profile, gait variability index, and walk ratio over three trials conducted at preferred walking speed (PWS) and during dual task walking.
There were statistically significant relationships (P ≤ .01) between TUG and 25’TW (R2 = 0.62). There were also significant relationships between 25’TW and digital parameters measured at PWS: velocity (R2 = 0.63); double support (R2 = 0.74); cadence (R2 = 0.56); and gait variability index (R2 = 0.54). During dual task walking, there were relationships between 25’TW and velocity (R2 = 0.53); double support (R2 = 0.30); cadence (R2 = 0.43); and gait variability index (R2 = 0.46).
TUG values were significantly associated with gait parameters during PWS: velocity (R2 = 0.71); double support (R2 = 0.75); cadence (R2 = 0.43); gait variability index (R2 = 0.45); and walk ratio (R2 = 0.06). During dual task walking, TUG values were significantly associated with velocity (R2 = 0.55), double support (R2 = 0.21), cadence (R2 = 0.45), and gait variability index (R2 = 0.39).
“With the availability multiple effective disease modifying therapies and the future potential of restorative or reparative treatments, more granular, validated standardized outcome measures are urgently needed,” said Dr. Gudesblatt. Analysis of gait cycle can provide clinically useful information not adequately captured by the current, more traditional approaches of measuring outcomes in MS.
Dr. Gudesblatt and Dr. Larochelle have no relevant financial disclosures.
“When you measure disability, what you really want to know is how things are changing in the patient’s life and not your perception of how they’re changing,” said Mark Gudesblatt, MD, who presented a study comparing the technique, called quantitative gait analysis, to other measures at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
The device, called Protokinetics, has been used in clinical studies for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, stroke, Friederich’s ataxia, and other conditions. The device is a digitized carpet that senses weight change and pressure as the individual walks.
“We can actually measure performance, and the performance is not just how fast you walk 25 feet. We’re measuring things that underlie how you walk: step length, step length variability, velocity, weight shift, how much time you spend on one leg. So it’s like listening to a symphony. We’re not measuring just the trumpets or the violins, we’re measuring everything,” said Dr. Gudesblatt, who is medical director of the Comprehensive MS Center at South Shore Neurologic Associates, Patchogue, N.Y.
Commonly used measures include the Expanded Disability Status Scale (EDSS), the 25-foot time walk (25’TW), and the Timed Up and Go (TUG).
Those measures are useful but don’t really measure up to clinical need, Dr. Gudesblatt said. “What you want is no evidence of disease activity, whether that’s multiple dimensions of thinking or multiple dimensions of walking, or changes on an MRI that are not the radiologist’s impression. Patients always say: ‘Doc, I’m worse.’ And we say: ‘Well, your exam is unchanged, your MRI has not changed. But they are worse for reasons – either their perception or their performance. So you can measure this very granularly, and you can relate it to their fear of falling, their balance confidence. This ups the game,” said Dr. Gudesblatt.
“And here’s where it gets even more interesting. You can use this for signatures of disease,” he added. The data can, for example, suggest that instead of Parkinson’s disease, a patient may have a Parkinson’s variant. “What we’re doing is showing how the 25-foot timed walk and Timed Up and Go are very traditional, conservative measures. They’re equivalent to the Pony Express. They’re good, but not where you want to be.”
Technology provides more sensitive, but more complex data
Digital tools to measure a variety of functions, including gait, cognition, and upper limb function are becoming increasingly common in MS, according to Catherine Larochelle, MD, PhD, who was asked for comment. “They are easily providing measures that are likely more sensitive and diverse and probably more meaningful about the daily functional status of a person than our usual EDSS,” said Dr. Larochelle, who is an associate professor at Université de Montréal.
The next step is to determine how best to use the complex data that such devices generate. “Lots of research is being done to better understand how to use the rich but complex data obtained with these tools to provide useful information to people with MS and their clinical team, to help guide shared clinical decisions, and likely accelerate and improve outcomes in clinical trials. So this is a very exciting new era in terms of clinical neurological assessment,” said Dr. Larochelle.
Granular gait analysis
Dr. Gudesblatt and colleagues analyzed retrospective data from 105 people with MS (69% female; average age, 53.7 years). Participants underwent all tests on the same day. The digital gait analysis captured velocity, double support, cadence, functional ambulation profile, gait variability index, and walk ratio over three trials conducted at preferred walking speed (PWS) and during dual task walking.
There were statistically significant relationships (P ≤ .01) between TUG and 25’TW (R2 = 0.62). There were also significant relationships between 25’TW and digital parameters measured at PWS: velocity (R2 = 0.63); double support (R2 = 0.74); cadence (R2 = 0.56); and gait variability index (R2 = 0.54). During dual task walking, there were relationships between 25’TW and velocity (R2 = 0.53); double support (R2 = 0.30); cadence (R2 = 0.43); and gait variability index (R2 = 0.46).
TUG values were significantly associated with gait parameters during PWS: velocity (R2 = 0.71); double support (R2 = 0.75); cadence (R2 = 0.43); gait variability index (R2 = 0.45); and walk ratio (R2 = 0.06). During dual task walking, TUG values were significantly associated with velocity (R2 = 0.55), double support (R2 = 0.21), cadence (R2 = 0.45), and gait variability index (R2 = 0.39).
“With the availability multiple effective disease modifying therapies and the future potential of restorative or reparative treatments, more granular, validated standardized outcome measures are urgently needed,” said Dr. Gudesblatt. Analysis of gait cycle can provide clinically useful information not adequately captured by the current, more traditional approaches of measuring outcomes in MS.
Dr. Gudesblatt and Dr. Larochelle have no relevant financial disclosures.
FROM ACTRIMS FORUM 2023
500 more steps a day tied to 14% lower CVD risk in older adults
Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.
“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.
The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.
The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.
Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.
Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.
Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.
The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).
In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).
Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.
However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.
Small steps may get patients started
Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.
“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.
“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.
More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”
Study fills research gap for older adults
“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.
“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.
“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.
Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.
The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.
Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.
“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.
The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.
The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.
Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.
Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.
Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.
The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).
In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).
Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.
However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.
Small steps may get patients started
Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.
“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.
“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.
More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”
Study fills research gap for older adults
“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.
“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.
“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.
Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.
The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.
Older adults who added a quarter mile of steps to their day showed a reduction in risk of cardiovascular events by 14% within 4 years, according to a study in more than 400 individuals.
“Aging is such a dynamic process, but most studies of daily steps and step goals are conducted on younger populations,” lead author Erin E. Dooley, PhD, an epidemiologist at the University of Alabama at Birmingham, said in an interview.
The impact of more modest step goals in older adults has not been well studied, Dr. Dooley said.
The population in the current study ranged from 71 to 92 years, with an average age of 78 years. The older age and relatively short follow-up period show the importance of steps and physical activity in older adults, she said.
Dr. Dooley presented the study at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.
She and her colleagues analyzed a subsample of participants in Atherosclerosis Risk in Communities (ARIC) study, an ongoing study conducted by the National Heart, Lung, and Blood Institute. The study population included 452 adults for whom step data were available at visit 6 of the ARIC study between 2016 and 2017. Participants wore an accelerometer on the waist for at least 10 hours a day for at least 3 days. The mean age of the participants was 78.4 years, 59% were women, and 20% were Black.
Outcomes were measured through December 2019 and included fatal and nonfatal cardiovascular disease (CVD) events of coronary heart disease, stroke, and heart failure.
Overall, each additional 500 steps per day was linked to a 14% reduction in risk of a CVD event (hazard ratio, 0.86; 95% confidence interval, 0.76-0.98). The mean step count was 3,447 steps per day, and 34 participants (7.5%) experienced a CVD event over 1,269 person-years of follow-up.
The cumulative risk of CVD was significantly higher (11.5%) in the quartile of adults with the lowest step count (defined as fewer than 2,077 steps per day), compared with 3.5% in those with the highest step count (defined as at least 4,453 steps per day).
In addition, adults in the highest quartile of steps had a 77% reduced risk of a proximal CVD (within 3.5 years) event over the study period (HR, 0.23).
Additional research is needed to explore whether increased steps prevent or delay CVD and whether low step counts may be a biomarker for underlying disease, the researchers noted in their abstract.
However, the results support the value of even a modest increase in activity to reduce CVD risk in older adults.
Small steps may get patients started
Dr. Dooley said she was surprised at the degree of benefits on heart health from 500 steps, and noted that the findings have clinical implications.
“Steps may be a more understandable metric for physical activity for patients than talking about moderate to vigorous intensity physical activity,” she said in an interview. “While we do not want to diminish the importance of higher intensity physical activity, encouraging small increases in the number of daily steps can also have great benefits for heart health.
“Steps are counted using a variety of devices and phones, so it may be helpful for patients to show clinicians their activity during well visits,” Dr. Dooley said. “Walking may also be more manageable for people as it is low impact. Achievable goals are also important. This study suggests that, for older adults, around 3,000 steps or more was associated with reduced CVD risk,” although the greatest benefits were seen with the most active group who averaged 4,500 or more steps per day.
More research is needed to show how steps may change over time, and how this relates to CVD and heart health,” she said. “At this time, we only had a single measure of physical activity.”
Study fills research gap for older adults
“Currently, the majority of the literature exploring a relationship between physical activity and the risk for developing cardiovascular disease has evaluated all adults together, not only those who are 70 year of age and older,” Monica C. Serra, PhD, of the University of Texas, San Antonio, said in an interview. “This study allows us to start to target specific cardiovascular recommendations for older adults.”.
“It is always exciting to see results from physical activity studies that continue to support prior evidence that even small amounts of physical activity are beneficial to cardiovascular health,” said Dr. Serra, who is also vice chair of the program committee for the meeting. “These results suggest that even if only small additions in physical activity are achievable, they may have cumulative benefits in reducing cardiovascular disease risk.” For clinicians, the results also provide targets that are easy for patients to understand, said Dr. Serra. Daily step counts allow clinicians to provide specific and measurable goals to help their older patients increase physical activity.
“Small additions in total daily step counts may have clinically meaningful benefits to heart health, so promoting their patients to make any slight changes that are able to be consistently incorporated into their schedule should be encouraged. This may be best monitored by encouraging the use of an activity tracker,” she said.
Although the current study adds to the literature with objective measures of physical activity utilizing accelerometers, these devices are not as sensitive at picking up activities such as bicycling or swimming, which may be more appropriate for some older adults with mobility limitations and chronic conditions, Dr. Serra said. Additional research is needed to assess the impact of other activities on CVD in the older population.
The meeting was sponsored by the American Heart Association. The study received no outside funding. Dr. Dooley and Dr. Serra had no financial conflicts to disclose.
FROM EPI/LIFESTYLE 2023
Cutting calories may benefit cognition in MS
SAN DIEGO – , new research suggests.
Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.
Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
High adherence rate
Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.
The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.
Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.
In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.
Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.
Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.
Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.
“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
Maintain healthy weight
The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.
There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.
Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.
However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.
She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
Superb study
Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.
“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.
Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.
The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – , new research suggests.
Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.
Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
High adherence rate
Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.
The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.
Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.
In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.
Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.
Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.
Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.
“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
Maintain healthy weight
The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.
There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.
Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.
However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.
She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
Superb study
Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.
“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.
Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.
The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – , new research suggests.
Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.
Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
High adherence rate
Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.
The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.
Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.
In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.
Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.
Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.
Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.
“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
Maintain healthy weight
The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.
There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.
Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.
However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.
She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
Superb study
Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.
“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.
Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.
The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ACTRIMS FORUM 2023
High level of psychiatric morbidity in prodromal MS
SAN DIEGO – new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.
These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.
With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Psychiatric morbidity during the prodromal phase of MS
Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.
Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.
The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.
The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.
The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.
The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.
Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.
It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.
In addition to psychiatric complaints, MS patients experience other symptoms, including pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.
Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.
He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
When does MS start?
Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.
He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”
Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.
The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.
These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.
With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Psychiatric morbidity during the prodromal phase of MS
Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.
Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.
The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.
The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.
The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.
The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.
Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.
It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.
In addition to psychiatric complaints, MS patients experience other symptoms, including pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.
Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.
He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
When does MS start?
Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.
He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”
Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.
The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.
These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.
With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.
The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Psychiatric morbidity during the prodromal phase of MS
Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.
Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.
The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.
The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.
The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.
The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.
Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.
It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.
In addition to psychiatric complaints, MS patients experience other symptoms, including pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.
Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.
He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
When does MS start?
Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.
He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”
Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.
The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ACTRIMS FORUM 2023
MOGAD: Immunotherapy predicts fewer relapses
SAN DIEGO – The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.
MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Predicting which patients will relapse
“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.
The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).
However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
The most effective treatment for relapsing MOGAD
In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.
Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.
Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.
He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.
“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
‘A good beginning’
The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.
“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.
Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.
SAN DIEGO – The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.
MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Predicting which patients will relapse
“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.
The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).
However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
The most effective treatment for relapsing MOGAD
In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.
Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.
Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.
He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.
“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
‘A good beginning’
The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.
“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.
Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.
SAN DIEGO – The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.
MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Predicting which patients will relapse
“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.
The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).
However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
The most effective treatment for relapsing MOGAD
In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.
Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.
Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.
He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.
“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
‘A good beginning’
The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.
“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.
Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.
At ACTRIMS FORUM 2023
Frequent cannabis use tied to coronary artery disease
In the first part, in an observational study, daily cannabis use was associated with 34% higher odds for CAD, compared with never-users, in a large population-based U.S. cohort. Less frequent use was not associated with increased odds for CAD.
In the second part, people with a genetic susceptibility to cannabis use disorder or severe cannabis dependency had an increased risk for CAD, compared with other people.
Ishan Paranjpe, MD, the study’s lead author, reported these results in a press briefing and will present the study at the upcoming joint scientific sessions of the American College of Cardiology and the World Heart Federation 2023.
“A couple of takeaway points are that daily cannabis use, but not less frequent cannabis use, was associated with CAD” in the large population-based cohort, said Dr. Paranjpe, a resident physician at Stanford (Calif.) University, during the press conference.
“This analysis was adjusted for several possible confounders including age, sex at birth, [body mass index (BMI)], race, education, cigarette use, hypertension, high cholesterol, and diabetes,” he noted, and even after accounting for these risk factors, the association with heart disease remained.
“And the next thing, using Mendelian randomization, we sort of implied that there might be a causal relationship between cannabis and heart disease. Importantly this effect is independent of alcohol and cigarette use.
“The notion that cannabis is completely benign is probably wrong, and there might be certain risk of certain cardiovascular effects of cannabis we should be more on the lookout for,” Dr. Paranjpe said in an interview.
“Our main conclusion was that prevalent CAD is associated with cannabis consumption,” he added. “Other mechanistic work published in Cell has also shown that cannabis causes vascular inflammation that may lead to CAD.
“Thus, there is growing evidence from both laboratory and population studies that cannabis consumption may be harmful for cardiovascular health,” he said. “However, we still need more work on whether it affects the risk of incident cardiovascular events (i.e., stroke, heart attack) in patient[s] with existing CAD.”
ASCVD risk
Invited to comment, Robert L. Page II, PharmD, chair of the writing group for the American Heart Association’s scientific statement Medical Marijuana, Recreational Cannabis, and Cardiovascular Health, published in 2020, said, “This adds to our hypothesis that if you are using marijuana over a longer period, greater exposure, you’re going to see an increase in the risk” for atherosclerotic cardiovascular disease (ASCVD).
“We’re seeing this increased risk for ASCVD in young adults between ages 18 to 40 – people who think that they’re invincible,” Dr. Page, a professor at the University of Colorado at Denver, Aurora, who was not involved with this research, told this news organization in an interview.
“The bottom line is that the risk that they are seeing is what has also been documented in other observational studies, and it adds fuel to the fire. We need to be paying close attention to this,” he said.
“Primary care [clinicians], cardiologists, need to address this, particularly in younger adults – because that’s where you’re seeing the highest amount of use.”
‘All of Us’ observational study
In the first part of the study, the researchers analyzed data from the “All of Us” cohort comprising adults age 18 and older from 340 inpatient and outpatient sites across the United States.
They identified 57,958 individuals who replied to a questionnaire asking about cannabis use (medicinal or recreational and whether it was edible or used by smoking or vaping) over the past 3 months.
There were 39,678 never-users, 8,749 who used it once or twice, 2,075 who used it monthly, 2,720 who used it weekly, and 4,736 who used it daily.
Of these, 3,506 individuals had CAD, based on medical records.
Only daily users had a significantly higher risk for CAD, compared with never-users (odds ratio, 1.34; P = .001) after adjusting for age, sex, hypertension, hyperlipidemia, type 2 diabetes, BMI, education, insurance status, and cigarette use.
The median age for daily users was 41, whereas the median age for never-users was 59.
GWAS analyses
The researchers then performed a Mendelian randomization analysis based on genome-wide association studies (GWAS) of cannabis use disorder and of CAD.
“Cannabis use disorder is a psychiatric diagnosis of severe cannabis dependency, equivalent to ‘alcohol use disorder’ for alcohol consumption,” Dr. Paranjpe explained. “The exact definition involves frequent use leading to significant dependence (but does not specify how often it is used).”
The GWAS data for cannabis use disorder came from a recent meta-analysis of three cohorts: the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE.
The GWAS statistics for CAD were obtained from the CARDIoGRAMplusC4D Consortium.
Cannabis use disorder was associated with significantly increased odds for CAD (OR, 1.05; P = .001), which remained after adjusting for both cigarette and alcohol use (OR, 1.04).
A version of this article first appeared on Medscape.com.
In the first part, in an observational study, daily cannabis use was associated with 34% higher odds for CAD, compared with never-users, in a large population-based U.S. cohort. Less frequent use was not associated with increased odds for CAD.
In the second part, people with a genetic susceptibility to cannabis use disorder or severe cannabis dependency had an increased risk for CAD, compared with other people.
Ishan Paranjpe, MD, the study’s lead author, reported these results in a press briefing and will present the study at the upcoming joint scientific sessions of the American College of Cardiology and the World Heart Federation 2023.
“A couple of takeaway points are that daily cannabis use, but not less frequent cannabis use, was associated with CAD” in the large population-based cohort, said Dr. Paranjpe, a resident physician at Stanford (Calif.) University, during the press conference.
“This analysis was adjusted for several possible confounders including age, sex at birth, [body mass index (BMI)], race, education, cigarette use, hypertension, high cholesterol, and diabetes,” he noted, and even after accounting for these risk factors, the association with heart disease remained.
“And the next thing, using Mendelian randomization, we sort of implied that there might be a causal relationship between cannabis and heart disease. Importantly this effect is independent of alcohol and cigarette use.
“The notion that cannabis is completely benign is probably wrong, and there might be certain risk of certain cardiovascular effects of cannabis we should be more on the lookout for,” Dr. Paranjpe said in an interview.
“Our main conclusion was that prevalent CAD is associated with cannabis consumption,” he added. “Other mechanistic work published in Cell has also shown that cannabis causes vascular inflammation that may lead to CAD.
“Thus, there is growing evidence from both laboratory and population studies that cannabis consumption may be harmful for cardiovascular health,” he said. “However, we still need more work on whether it affects the risk of incident cardiovascular events (i.e., stroke, heart attack) in patient[s] with existing CAD.”
ASCVD risk
Invited to comment, Robert L. Page II, PharmD, chair of the writing group for the American Heart Association’s scientific statement Medical Marijuana, Recreational Cannabis, and Cardiovascular Health, published in 2020, said, “This adds to our hypothesis that if you are using marijuana over a longer period, greater exposure, you’re going to see an increase in the risk” for atherosclerotic cardiovascular disease (ASCVD).
“We’re seeing this increased risk for ASCVD in young adults between ages 18 to 40 – people who think that they’re invincible,” Dr. Page, a professor at the University of Colorado at Denver, Aurora, who was not involved with this research, told this news organization in an interview.
“The bottom line is that the risk that they are seeing is what has also been documented in other observational studies, and it adds fuel to the fire. We need to be paying close attention to this,” he said.
“Primary care [clinicians], cardiologists, need to address this, particularly in younger adults – because that’s where you’re seeing the highest amount of use.”
‘All of Us’ observational study
In the first part of the study, the researchers analyzed data from the “All of Us” cohort comprising adults age 18 and older from 340 inpatient and outpatient sites across the United States.
They identified 57,958 individuals who replied to a questionnaire asking about cannabis use (medicinal or recreational and whether it was edible or used by smoking or vaping) over the past 3 months.
There were 39,678 never-users, 8,749 who used it once or twice, 2,075 who used it monthly, 2,720 who used it weekly, and 4,736 who used it daily.
Of these, 3,506 individuals had CAD, based on medical records.
Only daily users had a significantly higher risk for CAD, compared with never-users (odds ratio, 1.34; P = .001) after adjusting for age, sex, hypertension, hyperlipidemia, type 2 diabetes, BMI, education, insurance status, and cigarette use.
The median age for daily users was 41, whereas the median age for never-users was 59.
GWAS analyses
The researchers then performed a Mendelian randomization analysis based on genome-wide association studies (GWAS) of cannabis use disorder and of CAD.
“Cannabis use disorder is a psychiatric diagnosis of severe cannabis dependency, equivalent to ‘alcohol use disorder’ for alcohol consumption,” Dr. Paranjpe explained. “The exact definition involves frequent use leading to significant dependence (but does not specify how often it is used).”
The GWAS data for cannabis use disorder came from a recent meta-analysis of three cohorts: the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE.
The GWAS statistics for CAD were obtained from the CARDIoGRAMplusC4D Consortium.
Cannabis use disorder was associated with significantly increased odds for CAD (OR, 1.05; P = .001), which remained after adjusting for both cigarette and alcohol use (OR, 1.04).
A version of this article first appeared on Medscape.com.
In the first part, in an observational study, daily cannabis use was associated with 34% higher odds for CAD, compared with never-users, in a large population-based U.S. cohort. Less frequent use was not associated with increased odds for CAD.
In the second part, people with a genetic susceptibility to cannabis use disorder or severe cannabis dependency had an increased risk for CAD, compared with other people.
Ishan Paranjpe, MD, the study’s lead author, reported these results in a press briefing and will present the study at the upcoming joint scientific sessions of the American College of Cardiology and the World Heart Federation 2023.
“A couple of takeaway points are that daily cannabis use, but not less frequent cannabis use, was associated with CAD” in the large population-based cohort, said Dr. Paranjpe, a resident physician at Stanford (Calif.) University, during the press conference.
“This analysis was adjusted for several possible confounders including age, sex at birth, [body mass index (BMI)], race, education, cigarette use, hypertension, high cholesterol, and diabetes,” he noted, and even after accounting for these risk factors, the association with heart disease remained.
“And the next thing, using Mendelian randomization, we sort of implied that there might be a causal relationship between cannabis and heart disease. Importantly this effect is independent of alcohol and cigarette use.
“The notion that cannabis is completely benign is probably wrong, and there might be certain risk of certain cardiovascular effects of cannabis we should be more on the lookout for,” Dr. Paranjpe said in an interview.
“Our main conclusion was that prevalent CAD is associated with cannabis consumption,” he added. “Other mechanistic work published in Cell has also shown that cannabis causes vascular inflammation that may lead to CAD.
“Thus, there is growing evidence from both laboratory and population studies that cannabis consumption may be harmful for cardiovascular health,” he said. “However, we still need more work on whether it affects the risk of incident cardiovascular events (i.e., stroke, heart attack) in patient[s] with existing CAD.”
ASCVD risk
Invited to comment, Robert L. Page II, PharmD, chair of the writing group for the American Heart Association’s scientific statement Medical Marijuana, Recreational Cannabis, and Cardiovascular Health, published in 2020, said, “This adds to our hypothesis that if you are using marijuana over a longer period, greater exposure, you’re going to see an increase in the risk” for atherosclerotic cardiovascular disease (ASCVD).
“We’re seeing this increased risk for ASCVD in young adults between ages 18 to 40 – people who think that they’re invincible,” Dr. Page, a professor at the University of Colorado at Denver, Aurora, who was not involved with this research, told this news organization in an interview.
“The bottom line is that the risk that they are seeing is what has also been documented in other observational studies, and it adds fuel to the fire. We need to be paying close attention to this,” he said.
“Primary care [clinicians], cardiologists, need to address this, particularly in younger adults – because that’s where you’re seeing the highest amount of use.”
‘All of Us’ observational study
In the first part of the study, the researchers analyzed data from the “All of Us” cohort comprising adults age 18 and older from 340 inpatient and outpatient sites across the United States.
They identified 57,958 individuals who replied to a questionnaire asking about cannabis use (medicinal or recreational and whether it was edible or used by smoking or vaping) over the past 3 months.
There were 39,678 never-users, 8,749 who used it once or twice, 2,075 who used it monthly, 2,720 who used it weekly, and 4,736 who used it daily.
Of these, 3,506 individuals had CAD, based on medical records.
Only daily users had a significantly higher risk for CAD, compared with never-users (odds ratio, 1.34; P = .001) after adjusting for age, sex, hypertension, hyperlipidemia, type 2 diabetes, BMI, education, insurance status, and cigarette use.
The median age for daily users was 41, whereas the median age for never-users was 59.
GWAS analyses
The researchers then performed a Mendelian randomization analysis based on genome-wide association studies (GWAS) of cannabis use disorder and of CAD.
“Cannabis use disorder is a psychiatric diagnosis of severe cannabis dependency, equivalent to ‘alcohol use disorder’ for alcohol consumption,” Dr. Paranjpe explained. “The exact definition involves frequent use leading to significant dependence (but does not specify how often it is used).”
The GWAS data for cannabis use disorder came from a recent meta-analysis of three cohorts: the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE.
The GWAS statistics for CAD were obtained from the CARDIoGRAMplusC4D Consortium.
Cannabis use disorder was associated with significantly increased odds for CAD (OR, 1.05; P = .001), which remained after adjusting for both cigarette and alcohol use (OR, 1.04).
A version of this article first appeared on Medscape.com.
FROM ACC 2023
New data strengthen case for oral immunotherapy in tots
The buzz surrounding OIT – which involves ingesting daily doses of the culprit food to raise the threshold that would trigger a reaction – grew with the approval, by the U.S. Food and Drug Administration of Palforzia, of the peanut OIT pill in January 2020. Yet many allergists remained wary about the treatment, a monthslong regimen that can itself trigger allergic reactions.
Now, accumulating research points to “a possible window of opportunity early in life, less than 3 years of age, for more successful disease remission,” Justin Schwartz, MD, PhD, an allergist at Cincinnati Children’s Hospital, told a crowd at the annual meeting of the American Academy of Allergy, Asthma, & Immunology.
His presentation about OIT in toddlers kicked off a 3-hour clinical practice course, one of several dozen conference offerings highlighting this emerging approach.
Several AAAAI posters add to prior studies (for example, DEVIL and IMPACT) suggesting that OIT proceeds more smoothly and faster during a child’s earliest years – a season fraught with accidental exposures and reactions.
One poster described a retrospective study of 73 children younger than 4 years who underwent OIT at the Cleveland Clinic Food Allergy Center. Sixty-four were treated for peanut allergies, and seven patients received OIT for multiple foods, including tree nuts, milk, wheat, and sesame.
Of the 80 total OIT courses, 76 (95%) reached maintenance – meaning the child tolerated a small amount (for example, 1-2 peanuts) without reacting – in a median of 104 days (~3.4 months).
That is “quite impressive,” said allergist Hugh Windom, MD, whose clinic in Sarasota, Fla., has offered OIT since 2012.
Older children typically have 80%-90% success and take longer (6-8 months) to reach maintenance because of busier schedules and reactions that slow them down, he said. In his clinic’s larger retrospective analysis of preschool-aged OIT patients, presented at the 2022 AAAAI meeting, 89% of patients with peanut allergies and 72% of children with multiple food allergies achieved maintenance.
In the Cleveland Clinic study, children with favorable lab test results after receiving the maintenance dose for 6 months were offered an oral food challenge. Of 24 patients who completed the challenge, 75% “passed with a normal serving size of the treated food (for example, two tablespoons of peanut butter),” Sarah Johnson, MD, lead author and Cleveland Clinic allergy/immunology fellow, said in an interview.
Plus, OIT seemed safer for toddlers. Although 41% of the children had reactions during clinic updosing and 48% had reactions at home, only ~3% of toddler OIT courses required epinephrine. By comparison, ~11% of treatments required epinephrine in a large OIT study of older children.
When a child reacts, “you might keep them on the dose or go a little slower,” said Johnson, who worked with allergist Jaclyn Bjelac, MD, on the study. These setbacks occurred less frequently in toddlers, allowing their OIT to “go a lot faster” than in older children. And so far, Dr. Johnson said, none of the toddlers have shown signs of eosinophilic esophagitis, a rare complication that can develop during OIT.
A smaller analysis of real-world outcomes in an academic clinical setting also found that OIT was well tolerated at very young ages. Since 2020, this ongoing study at UVA Children’s Hospital in Charlottesville has enrolled 22 peanut-allergic children (aged 6 months to 3 years) for OIT. Three patients have dropped out, four are in the buildup phrase, and 15 have reached maintenance dosing. None have reported having to use epinephrine.
Three patients have completed 1 year of maintenance therapy, and another patient accidentally consumed ~3,000 mg of peanut protein (equivalent to ~10 peanuts) after 5 months of maintenance. All four “now incorporate peanut into their diets ad lib,” according to lead author and allergist Jonathan Hemler, MD, who directs the UVA pediatric food allergy program.
These findings are “really reassuring – because even if you may not offer OIT, you’re still going to get questions about it,” said Ama Alexis, MD, an allergist/immunologist in private practice in New York and a clinical assistant professor at NYU Grossmann School of Medicine, commenting on the Cleveland Clinic study.
“It’s great that we’re hearing and seeing so much about OIT,” she added. While training as an allergy/immunology fellow 15 years ago, many saw the treatment as dangerous – “an absolute no-no,” she said.
The AAAAI still considers OIT “investigational,” yet this year’s annual meeting featured 22 posters – plus a course, workshop, seminar, and oral abstract session – on the approach.
The “thought process has shifted,” Dr. Alexis said. “It’s good to see all these numbers, these results. I think once you’re comfortable, you should embrace new therapies.”
Dr. Schwartz has consulted for Shire/Takeda and has received research funding from Knopp Biosciences. Dr. Alexis consults for AbbVie, serves on advisory boards for Jansen and Eli Lilli, and is a member of Pfizer’s advisory board and speaker’s bureau. Dr. Johnson, Dr. Windom, and Dr. Hemler report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The buzz surrounding OIT – which involves ingesting daily doses of the culprit food to raise the threshold that would trigger a reaction – grew with the approval, by the U.S. Food and Drug Administration of Palforzia, of the peanut OIT pill in January 2020. Yet many allergists remained wary about the treatment, a monthslong regimen that can itself trigger allergic reactions.
Now, accumulating research points to “a possible window of opportunity early in life, less than 3 years of age, for more successful disease remission,” Justin Schwartz, MD, PhD, an allergist at Cincinnati Children’s Hospital, told a crowd at the annual meeting of the American Academy of Allergy, Asthma, & Immunology.
His presentation about OIT in toddlers kicked off a 3-hour clinical practice course, one of several dozen conference offerings highlighting this emerging approach.
Several AAAAI posters add to prior studies (for example, DEVIL and IMPACT) suggesting that OIT proceeds more smoothly and faster during a child’s earliest years – a season fraught with accidental exposures and reactions.
One poster described a retrospective study of 73 children younger than 4 years who underwent OIT at the Cleveland Clinic Food Allergy Center. Sixty-four were treated for peanut allergies, and seven patients received OIT for multiple foods, including tree nuts, milk, wheat, and sesame.
Of the 80 total OIT courses, 76 (95%) reached maintenance – meaning the child tolerated a small amount (for example, 1-2 peanuts) without reacting – in a median of 104 days (~3.4 months).
That is “quite impressive,” said allergist Hugh Windom, MD, whose clinic in Sarasota, Fla., has offered OIT since 2012.
Older children typically have 80%-90% success and take longer (6-8 months) to reach maintenance because of busier schedules and reactions that slow them down, he said. In his clinic’s larger retrospective analysis of preschool-aged OIT patients, presented at the 2022 AAAAI meeting, 89% of patients with peanut allergies and 72% of children with multiple food allergies achieved maintenance.
In the Cleveland Clinic study, children with favorable lab test results after receiving the maintenance dose for 6 months were offered an oral food challenge. Of 24 patients who completed the challenge, 75% “passed with a normal serving size of the treated food (for example, two tablespoons of peanut butter),” Sarah Johnson, MD, lead author and Cleveland Clinic allergy/immunology fellow, said in an interview.
Plus, OIT seemed safer for toddlers. Although 41% of the children had reactions during clinic updosing and 48% had reactions at home, only ~3% of toddler OIT courses required epinephrine. By comparison, ~11% of treatments required epinephrine in a large OIT study of older children.
When a child reacts, “you might keep them on the dose or go a little slower,” said Johnson, who worked with allergist Jaclyn Bjelac, MD, on the study. These setbacks occurred less frequently in toddlers, allowing their OIT to “go a lot faster” than in older children. And so far, Dr. Johnson said, none of the toddlers have shown signs of eosinophilic esophagitis, a rare complication that can develop during OIT.
A smaller analysis of real-world outcomes in an academic clinical setting also found that OIT was well tolerated at very young ages. Since 2020, this ongoing study at UVA Children’s Hospital in Charlottesville has enrolled 22 peanut-allergic children (aged 6 months to 3 years) for OIT. Three patients have dropped out, four are in the buildup phrase, and 15 have reached maintenance dosing. None have reported having to use epinephrine.
Three patients have completed 1 year of maintenance therapy, and another patient accidentally consumed ~3,000 mg of peanut protein (equivalent to ~10 peanuts) after 5 months of maintenance. All four “now incorporate peanut into their diets ad lib,” according to lead author and allergist Jonathan Hemler, MD, who directs the UVA pediatric food allergy program.
These findings are “really reassuring – because even if you may not offer OIT, you’re still going to get questions about it,” said Ama Alexis, MD, an allergist/immunologist in private practice in New York and a clinical assistant professor at NYU Grossmann School of Medicine, commenting on the Cleveland Clinic study.
“It’s great that we’re hearing and seeing so much about OIT,” she added. While training as an allergy/immunology fellow 15 years ago, many saw the treatment as dangerous – “an absolute no-no,” she said.
The AAAAI still considers OIT “investigational,” yet this year’s annual meeting featured 22 posters – plus a course, workshop, seminar, and oral abstract session – on the approach.
The “thought process has shifted,” Dr. Alexis said. “It’s good to see all these numbers, these results. I think once you’re comfortable, you should embrace new therapies.”
Dr. Schwartz has consulted for Shire/Takeda and has received research funding from Knopp Biosciences. Dr. Alexis consults for AbbVie, serves on advisory boards for Jansen and Eli Lilli, and is a member of Pfizer’s advisory board and speaker’s bureau. Dr. Johnson, Dr. Windom, and Dr. Hemler report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The buzz surrounding OIT – which involves ingesting daily doses of the culprit food to raise the threshold that would trigger a reaction – grew with the approval, by the U.S. Food and Drug Administration of Palforzia, of the peanut OIT pill in January 2020. Yet many allergists remained wary about the treatment, a monthslong regimen that can itself trigger allergic reactions.
Now, accumulating research points to “a possible window of opportunity early in life, less than 3 years of age, for more successful disease remission,” Justin Schwartz, MD, PhD, an allergist at Cincinnati Children’s Hospital, told a crowd at the annual meeting of the American Academy of Allergy, Asthma, & Immunology.
His presentation about OIT in toddlers kicked off a 3-hour clinical practice course, one of several dozen conference offerings highlighting this emerging approach.
Several AAAAI posters add to prior studies (for example, DEVIL and IMPACT) suggesting that OIT proceeds more smoothly and faster during a child’s earliest years – a season fraught with accidental exposures and reactions.
One poster described a retrospective study of 73 children younger than 4 years who underwent OIT at the Cleveland Clinic Food Allergy Center. Sixty-four were treated for peanut allergies, and seven patients received OIT for multiple foods, including tree nuts, milk, wheat, and sesame.
Of the 80 total OIT courses, 76 (95%) reached maintenance – meaning the child tolerated a small amount (for example, 1-2 peanuts) without reacting – in a median of 104 days (~3.4 months).
That is “quite impressive,” said allergist Hugh Windom, MD, whose clinic in Sarasota, Fla., has offered OIT since 2012.
Older children typically have 80%-90% success and take longer (6-8 months) to reach maintenance because of busier schedules and reactions that slow them down, he said. In his clinic’s larger retrospective analysis of preschool-aged OIT patients, presented at the 2022 AAAAI meeting, 89% of patients with peanut allergies and 72% of children with multiple food allergies achieved maintenance.
In the Cleveland Clinic study, children with favorable lab test results after receiving the maintenance dose for 6 months were offered an oral food challenge. Of 24 patients who completed the challenge, 75% “passed with a normal serving size of the treated food (for example, two tablespoons of peanut butter),” Sarah Johnson, MD, lead author and Cleveland Clinic allergy/immunology fellow, said in an interview.
Plus, OIT seemed safer for toddlers. Although 41% of the children had reactions during clinic updosing and 48% had reactions at home, only ~3% of toddler OIT courses required epinephrine. By comparison, ~11% of treatments required epinephrine in a large OIT study of older children.
When a child reacts, “you might keep them on the dose or go a little slower,” said Johnson, who worked with allergist Jaclyn Bjelac, MD, on the study. These setbacks occurred less frequently in toddlers, allowing their OIT to “go a lot faster” than in older children. And so far, Dr. Johnson said, none of the toddlers have shown signs of eosinophilic esophagitis, a rare complication that can develop during OIT.
A smaller analysis of real-world outcomes in an academic clinical setting also found that OIT was well tolerated at very young ages. Since 2020, this ongoing study at UVA Children’s Hospital in Charlottesville has enrolled 22 peanut-allergic children (aged 6 months to 3 years) for OIT. Three patients have dropped out, four are in the buildup phrase, and 15 have reached maintenance dosing. None have reported having to use epinephrine.
Three patients have completed 1 year of maintenance therapy, and another patient accidentally consumed ~3,000 mg of peanut protein (equivalent to ~10 peanuts) after 5 months of maintenance. All four “now incorporate peanut into their diets ad lib,” according to lead author and allergist Jonathan Hemler, MD, who directs the UVA pediatric food allergy program.
These findings are “really reassuring – because even if you may not offer OIT, you’re still going to get questions about it,” said Ama Alexis, MD, an allergist/immunologist in private practice in New York and a clinical assistant professor at NYU Grossmann School of Medicine, commenting on the Cleveland Clinic study.
“It’s great that we’re hearing and seeing so much about OIT,” she added. While training as an allergy/immunology fellow 15 years ago, many saw the treatment as dangerous – “an absolute no-no,” she said.
The AAAAI still considers OIT “investigational,” yet this year’s annual meeting featured 22 posters – plus a course, workshop, seminar, and oral abstract session – on the approach.
The “thought process has shifted,” Dr. Alexis said. “It’s good to see all these numbers, these results. I think once you’re comfortable, you should embrace new therapies.”
Dr. Schwartz has consulted for Shire/Takeda and has received research funding from Knopp Biosciences. Dr. Alexis consults for AbbVie, serves on advisory boards for Jansen and Eli Lilli, and is a member of Pfizer’s advisory board and speaker’s bureau. Dr. Johnson, Dr. Windom, and Dr. Hemler report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAAAI 2023
Prostate cancer subgroup may benefit from intensified therapy
SAN FRANCISCO – For patients with prostate cancer who have unfavorable features and a detectable PSA following a radical prostatectomy, the standard of care is treatment with 6 months of a gonadotropin-releasing hormone (GnRH) agonist with salvage radiation therapy (SRT), as established by the GETUG-AFU 16 trial.
A new trial, dubbed FORMULA-509, explored whether outcomes could be improved by intensifying the drug treatment by adding 6 months of abiraterone acetate plus prednisone as well as apalutamide on top of the GnRH agonist alongside the salvage radiotherapy.
However, the combination did significantly improve PFS and MFS in a subset of men with PSA levels greater than 0.5 ng/mL.
“Although this primary analysis did not meet the prespecified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy plus 6 months of ADT [androgen deprivation therapy] may improve progression-free survival and metastasis-free survival,” said lead author Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston, and professor of radiation oncology at Harvard Medical School.
“This may be particularly evident in the subgroup of patients with PSA greater that 0.5 ng/mL where a preplanned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival,” he said. “Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy.”
The study results were presented at the ASCO Genitourinary Cancers Symposium.
Benefit in subset
The FORMULA-509 trial included 305 patients with PSA ≥ 0.1 ng/mL who had undergone a radical prostatectomy, and who had one or more unfavorable risk features (Gleason 8-10 disease, PSA > 0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time < 10 months, negative margins, persistent PSA, gross local/regional disease).
“This was a pretty high-risk population,” Dr. Nguyen emphasized, as 35% had Gleason score of 9, about a third (31%) a PSA >0.5, and 29% were pathologic node positive.
All patients received salvage radiotherapy plus 6 months of GnRH agonist (bicalutamide 50 mg), and half were randomly assigned to also receive abiraterone acetate/prednisone 1,000 mg/5 mg + apalutamide 240 mg daily.
At a median follow-up of 34 months, the 3-year PFS rate was 74.9% in the AAP-apalutamide arm vs. 68.5% for the control group (hazard ratio [HR], 0.71; P = .06), and the 3-year MFS rate was 90.6% vs. 87.2%, respectively (HR, 0.57; P = .05).
In the subset of patients with a PSA greater than 0.5 ng/mL, the 3-year PFS and MFS rates were significantly higher with in the AAP-apalutamide group: the 3-year PFS rate was 67.2% vs. 46.8% (HR, 0.50; P = .03), and the 3-year MFS rate was 84.3% vs. 66.1% (HR, 0.32; P = .02).
Adverse events were consistent with the known safety profiles of the agents being studied, Dr. Nguyen noted. The most common toxicities for AAP-apalutamide vs. controls were hypertension (21.8% vs. 13.3%), maculopapular rash (11.5% vs. 0.6%), diarrhea (8.5% vs. 4.8%), and fatigue (7.9% vs. 6.1%).
Dr. Nguyen noted that even though “we’re not supposed to compare clinical trials,” the results of this study appeared to compare favorably with those of another trial, RADICALS-HD, which was presented at the 2022 European Society of Medical Oncology Congress. That study showed that in patients undergoing postoperative radiation therapy, 24 months of ADT was superior to 6 months of ADT in improving both time to salvage ADT and MFS.
However, Dr. Nguyen emphasized that it would have to be formally tested, to see if “FORMULA-509 is performing in the ballpark of what 24 months of ADT would do.
“And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark,” he said. “So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months.”
He added that this concept would be formally tested in the upcoming PROSTATE IQ study.
Strong evidence, standardization needed
In a discussion of the paper, Tyler Seibert, MD, PhD, of the University of California San Diego, said that “escalation by 24 months has the strongest evidence today, specifically from the RADICALS-HD trial, with more than 1,500 men with 10 years of follow-up and a clear statistically significant result.
“Intensification for 6 months is a very compelling concept, as most patients are not getting 2 years of androgen deprivation therapy at this point post prostatectomy,” he continued. “While we await the long term follow-up of this study and the pending PROSTATE IQ trial, and if only 6 months of therapy is acceptable or feasible, the FORMULA-509 [trial] provides convincing evidence that select patients would benefit from intensification with AAP and apalutamide.”
Another expert weighed in on the data. Approached by this news organization for an independent comment, Jeff M. Michalski, MD, MBA, professor of radiation oncology at Washington University, St Louis, and president of the American Society of Radiation Oncology, noted a few issues in the study.
He said that standards had changed since this study was first approved and had begun accrual several years ago. “In context of today’s era, the current standard is to do a PET scan if patients have a chemical failure after surgery,” he said. “The PSA levels of patients who were treated [in this trial] were very high, and many patients do not want to wait until they reach that level.”
Dr. Michalski also pointed out the number of patients getting radiation was less than the number who had node-positive disease. “This shows that patients had received suboptimal therapy late in the disease,” he said.
Overall, most patients in the study did not receive lymph node radiation, even though they had high-risk features. “A recent study of almost 1,800 patients that was published in The Lancet found that there is a benefit to pelvic lymph node radiation,” he said. “Because it wasn’t mandated, most of the patients did not receive pelvic lymph node radiation, which we now understand offers some benefit.”
The reasons for not giving pelvic radiation to these men is unclear. “Treatment was left at the discretion of the physician and this could create bias,” Dr. Michalski said. “It could drive one arm more than another.”
The study also wasn’t controlled for pelvic radiation. “Most of the nodal positive patients received it, but the other patients were undertreated,” he noted.
Dr. Michalski added that he hopes that in the forthcoming PROSTATE IQ study, lymph node radiation and imaging are standardized.
The trial was supported by Janssen Oncology. Dr. Nguyen disclosed relationships with, and/or support from, Volatilyx, Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences, Astellas Pharma, and Janssen. Dr. Seibert disclosed relationships with, and/or support from, CorTechs Labs, Varian Medical Systems, and GE Healthcare.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – For patients with prostate cancer who have unfavorable features and a detectable PSA following a radical prostatectomy, the standard of care is treatment with 6 months of a gonadotropin-releasing hormone (GnRH) agonist with salvage radiation therapy (SRT), as established by the GETUG-AFU 16 trial.
A new trial, dubbed FORMULA-509, explored whether outcomes could be improved by intensifying the drug treatment by adding 6 months of abiraterone acetate plus prednisone as well as apalutamide on top of the GnRH agonist alongside the salvage radiotherapy.
However, the combination did significantly improve PFS and MFS in a subset of men with PSA levels greater than 0.5 ng/mL.
“Although this primary analysis did not meet the prespecified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy plus 6 months of ADT [androgen deprivation therapy] may improve progression-free survival and metastasis-free survival,” said lead author Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston, and professor of radiation oncology at Harvard Medical School.
“This may be particularly evident in the subgroup of patients with PSA greater that 0.5 ng/mL where a preplanned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival,” he said. “Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy.”
The study results were presented at the ASCO Genitourinary Cancers Symposium.
Benefit in subset
The FORMULA-509 trial included 305 patients with PSA ≥ 0.1 ng/mL who had undergone a radical prostatectomy, and who had one or more unfavorable risk features (Gleason 8-10 disease, PSA > 0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time < 10 months, negative margins, persistent PSA, gross local/regional disease).
“This was a pretty high-risk population,” Dr. Nguyen emphasized, as 35% had Gleason score of 9, about a third (31%) a PSA >0.5, and 29% were pathologic node positive.
All patients received salvage radiotherapy plus 6 months of GnRH agonist (bicalutamide 50 mg), and half were randomly assigned to also receive abiraterone acetate/prednisone 1,000 mg/5 mg + apalutamide 240 mg daily.
At a median follow-up of 34 months, the 3-year PFS rate was 74.9% in the AAP-apalutamide arm vs. 68.5% for the control group (hazard ratio [HR], 0.71; P = .06), and the 3-year MFS rate was 90.6% vs. 87.2%, respectively (HR, 0.57; P = .05).
In the subset of patients with a PSA greater than 0.5 ng/mL, the 3-year PFS and MFS rates were significantly higher with in the AAP-apalutamide group: the 3-year PFS rate was 67.2% vs. 46.8% (HR, 0.50; P = .03), and the 3-year MFS rate was 84.3% vs. 66.1% (HR, 0.32; P = .02).
Adverse events were consistent with the known safety profiles of the agents being studied, Dr. Nguyen noted. The most common toxicities for AAP-apalutamide vs. controls were hypertension (21.8% vs. 13.3%), maculopapular rash (11.5% vs. 0.6%), diarrhea (8.5% vs. 4.8%), and fatigue (7.9% vs. 6.1%).
Dr. Nguyen noted that even though “we’re not supposed to compare clinical trials,” the results of this study appeared to compare favorably with those of another trial, RADICALS-HD, which was presented at the 2022 European Society of Medical Oncology Congress. That study showed that in patients undergoing postoperative radiation therapy, 24 months of ADT was superior to 6 months of ADT in improving both time to salvage ADT and MFS.
However, Dr. Nguyen emphasized that it would have to be formally tested, to see if “FORMULA-509 is performing in the ballpark of what 24 months of ADT would do.
“And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark,” he said. “So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months.”
He added that this concept would be formally tested in the upcoming PROSTATE IQ study.
Strong evidence, standardization needed
In a discussion of the paper, Tyler Seibert, MD, PhD, of the University of California San Diego, said that “escalation by 24 months has the strongest evidence today, specifically from the RADICALS-HD trial, with more than 1,500 men with 10 years of follow-up and a clear statistically significant result.
“Intensification for 6 months is a very compelling concept, as most patients are not getting 2 years of androgen deprivation therapy at this point post prostatectomy,” he continued. “While we await the long term follow-up of this study and the pending PROSTATE IQ trial, and if only 6 months of therapy is acceptable or feasible, the FORMULA-509 [trial] provides convincing evidence that select patients would benefit from intensification with AAP and apalutamide.”
Another expert weighed in on the data. Approached by this news organization for an independent comment, Jeff M. Michalski, MD, MBA, professor of radiation oncology at Washington University, St Louis, and president of the American Society of Radiation Oncology, noted a few issues in the study.
He said that standards had changed since this study was first approved and had begun accrual several years ago. “In context of today’s era, the current standard is to do a PET scan if patients have a chemical failure after surgery,” he said. “The PSA levels of patients who were treated [in this trial] were very high, and many patients do not want to wait until they reach that level.”
Dr. Michalski also pointed out the number of patients getting radiation was less than the number who had node-positive disease. “This shows that patients had received suboptimal therapy late in the disease,” he said.
Overall, most patients in the study did not receive lymph node radiation, even though they had high-risk features. “A recent study of almost 1,800 patients that was published in The Lancet found that there is a benefit to pelvic lymph node radiation,” he said. “Because it wasn’t mandated, most of the patients did not receive pelvic lymph node radiation, which we now understand offers some benefit.”
The reasons for not giving pelvic radiation to these men is unclear. “Treatment was left at the discretion of the physician and this could create bias,” Dr. Michalski said. “It could drive one arm more than another.”
The study also wasn’t controlled for pelvic radiation. “Most of the nodal positive patients received it, but the other patients were undertreated,” he noted.
Dr. Michalski added that he hopes that in the forthcoming PROSTATE IQ study, lymph node radiation and imaging are standardized.
The trial was supported by Janssen Oncology. Dr. Nguyen disclosed relationships with, and/or support from, Volatilyx, Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences, Astellas Pharma, and Janssen. Dr. Seibert disclosed relationships with, and/or support from, CorTechs Labs, Varian Medical Systems, and GE Healthcare.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – For patients with prostate cancer who have unfavorable features and a detectable PSA following a radical prostatectomy, the standard of care is treatment with 6 months of a gonadotropin-releasing hormone (GnRH) agonist with salvage radiation therapy (SRT), as established by the GETUG-AFU 16 trial.
A new trial, dubbed FORMULA-509, explored whether outcomes could be improved by intensifying the drug treatment by adding 6 months of abiraterone acetate plus prednisone as well as apalutamide on top of the GnRH agonist alongside the salvage radiotherapy.
However, the combination did significantly improve PFS and MFS in a subset of men with PSA levels greater than 0.5 ng/mL.
“Although this primary analysis did not meet the prespecified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy plus 6 months of ADT [androgen deprivation therapy] may improve progression-free survival and metastasis-free survival,” said lead author Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston, and professor of radiation oncology at Harvard Medical School.
“This may be particularly evident in the subgroup of patients with PSA greater that 0.5 ng/mL where a preplanned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival,” he said. “Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy.”
The study results were presented at the ASCO Genitourinary Cancers Symposium.
Benefit in subset
The FORMULA-509 trial included 305 patients with PSA ≥ 0.1 ng/mL who had undergone a radical prostatectomy, and who had one or more unfavorable risk features (Gleason 8-10 disease, PSA > 0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time < 10 months, negative margins, persistent PSA, gross local/regional disease).
“This was a pretty high-risk population,” Dr. Nguyen emphasized, as 35% had Gleason score of 9, about a third (31%) a PSA >0.5, and 29% were pathologic node positive.
All patients received salvage radiotherapy plus 6 months of GnRH agonist (bicalutamide 50 mg), and half were randomly assigned to also receive abiraterone acetate/prednisone 1,000 mg/5 mg + apalutamide 240 mg daily.
At a median follow-up of 34 months, the 3-year PFS rate was 74.9% in the AAP-apalutamide arm vs. 68.5% for the control group (hazard ratio [HR], 0.71; P = .06), and the 3-year MFS rate was 90.6% vs. 87.2%, respectively (HR, 0.57; P = .05).
In the subset of patients with a PSA greater than 0.5 ng/mL, the 3-year PFS and MFS rates were significantly higher with in the AAP-apalutamide group: the 3-year PFS rate was 67.2% vs. 46.8% (HR, 0.50; P = .03), and the 3-year MFS rate was 84.3% vs. 66.1% (HR, 0.32; P = .02).
Adverse events were consistent with the known safety profiles of the agents being studied, Dr. Nguyen noted. The most common toxicities for AAP-apalutamide vs. controls were hypertension (21.8% vs. 13.3%), maculopapular rash (11.5% vs. 0.6%), diarrhea (8.5% vs. 4.8%), and fatigue (7.9% vs. 6.1%).
Dr. Nguyen noted that even though “we’re not supposed to compare clinical trials,” the results of this study appeared to compare favorably with those of another trial, RADICALS-HD, which was presented at the 2022 European Society of Medical Oncology Congress. That study showed that in patients undergoing postoperative radiation therapy, 24 months of ADT was superior to 6 months of ADT in improving both time to salvage ADT and MFS.
However, Dr. Nguyen emphasized that it would have to be formally tested, to see if “FORMULA-509 is performing in the ballpark of what 24 months of ADT would do.
“And I think that compared to 6 months of ADT, we can say it is certainly performing in the ballpark,” he said. “So, for patients with higher risk features, intensifying 6 months of ADT, I think, may be an appealing alternative to lengthening the ADT duration to 24 months.”
He added that this concept would be formally tested in the upcoming PROSTATE IQ study.
Strong evidence, standardization needed
In a discussion of the paper, Tyler Seibert, MD, PhD, of the University of California San Diego, said that “escalation by 24 months has the strongest evidence today, specifically from the RADICALS-HD trial, with more than 1,500 men with 10 years of follow-up and a clear statistically significant result.
“Intensification for 6 months is a very compelling concept, as most patients are not getting 2 years of androgen deprivation therapy at this point post prostatectomy,” he continued. “While we await the long term follow-up of this study and the pending PROSTATE IQ trial, and if only 6 months of therapy is acceptable or feasible, the FORMULA-509 [trial] provides convincing evidence that select patients would benefit from intensification with AAP and apalutamide.”
Another expert weighed in on the data. Approached by this news organization for an independent comment, Jeff M. Michalski, MD, MBA, professor of radiation oncology at Washington University, St Louis, and president of the American Society of Radiation Oncology, noted a few issues in the study.
He said that standards had changed since this study was first approved and had begun accrual several years ago. “In context of today’s era, the current standard is to do a PET scan if patients have a chemical failure after surgery,” he said. “The PSA levels of patients who were treated [in this trial] were very high, and many patients do not want to wait until they reach that level.”
Dr. Michalski also pointed out the number of patients getting radiation was less than the number who had node-positive disease. “This shows that patients had received suboptimal therapy late in the disease,” he said.
Overall, most patients in the study did not receive lymph node radiation, even though they had high-risk features. “A recent study of almost 1,800 patients that was published in The Lancet found that there is a benefit to pelvic lymph node radiation,” he said. “Because it wasn’t mandated, most of the patients did not receive pelvic lymph node radiation, which we now understand offers some benefit.”
The reasons for not giving pelvic radiation to these men is unclear. “Treatment was left at the discretion of the physician and this could create bias,” Dr. Michalski said. “It could drive one arm more than another.”
The study also wasn’t controlled for pelvic radiation. “Most of the nodal positive patients received it, but the other patients were undertreated,” he noted.
Dr. Michalski added that he hopes that in the forthcoming PROSTATE IQ study, lymph node radiation and imaging are standardized.
The trial was supported by Janssen Oncology. Dr. Nguyen disclosed relationships with, and/or support from, Volatilyx, Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences, Astellas Pharma, and Janssen. Dr. Seibert disclosed relationships with, and/or support from, CorTechs Labs, Varian Medical Systems, and GE Healthcare.
A version of this article first appeared on Medscape.com.
AT ASCO GU 2023
Expert dispels myths about hair care in patients with skin of color
HONOLULU –
“This is false,” Dr. Heath, director of pediatric dermatology at Temple University, Philadelphia, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! With little manipulation, length may be retained, since tightly coiled hair has a higher likelihood of breakage, she said. “But washing the scalp and hair is recommended for tightly coiled hair weekly or every other week. Exclusively co-washing – a technique where hair conditioner is used instead of shampooing – is also not advised due to scalp build-up.”
Other myths she addressed include the following:
“I have a weak spot (or stress spot) on the top of my scalp.” These terms may be used to describe hair on a spot that goes through cycles of breaking off and re-growing. This is false. “If someone were to say that, and we see short hairs on the top of a patient’s scalp, with or without tenderness, pruritus, or pain, we want to recognize that as possibly an early sign of central centrifugal cicatricial alopecia [CCCA],” she said. “We want to pick up cases of CCCA forme fruste [central hair breakage] early.”
Medicated shampoos are helpful for all patients with seborrheic dermatitis. This notion is more complicated. “In theory, medicated shampoos like ketoconazole should be helpful, but if the shampoos are too drying for the hair and they cause further hair breakage, that’s going to be a problem as well,” explained Dr. Heath, who was the senior author of an article on how to address common conditions affecting pediatric and adolescent patients with skin of color. For patients with tightly coiled hair, she recommends applying antifungal shampoos to the scalp only, waiting 5-10 minutes, rinsing, and shampooing the scalp and hair with a moisturizing shampoo and rinsing. They can then condition with a moisturizing conditioner and style their hair as desired.
Don’t touch a Black woman’s hair. That unwritten rule may apply to a woman you pass on the street, she said, but not during clinical exams in cases where clinicians and patients seeking hair loss treatment have different hair types. “Touch the hair; don’t do a lean-in exam,” emphasized Dr. Heath, who is the inaugural faculty scholar at Temple University Lewis Katz School of Medicine’s Office of Health Equity Diversity, and Inclusion. “You want to perform the scalp and hair exam with cultural humility.” Understanding the patient’s hair care goals and perspective allows dermatologists to take a more individualized approach to their concerns, especially in race-discordant patient-physician interactions.
Going natural (chemical-free) will solve scarring hair loss problems. This is false. “Genetic defects in the hair shaft have been described as the cause of some CCCA cases, so we need to stop solely blaming the patient for that condition,” she said. Dr. Heath noted that the transition point between natural hair and relaxed hair is highly prone to breakage. She suggests low or lower tension options such as knotless braids, and crochet hairstyles, and when patients have locs, they should be shoulder length or higher to reduce tension.
Dr. Heath disclosed that she has served as a consultant or adviser for Arcutis, CeraVe, Janssen Pharmaceuticals, Johnson & Johnson Pharmaceutical Research & Development, Leo, Lilly, Pfizer, and Regeneron Pharmaceuticals.
Medscape and this news organization are owned by the same parent company.
HONOLULU –
“This is false,” Dr. Heath, director of pediatric dermatology at Temple University, Philadelphia, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! With little manipulation, length may be retained, since tightly coiled hair has a higher likelihood of breakage, she said. “But washing the scalp and hair is recommended for tightly coiled hair weekly or every other week. Exclusively co-washing – a technique where hair conditioner is used instead of shampooing – is also not advised due to scalp build-up.”
Other myths she addressed include the following:
“I have a weak spot (or stress spot) on the top of my scalp.” These terms may be used to describe hair on a spot that goes through cycles of breaking off and re-growing. This is false. “If someone were to say that, and we see short hairs on the top of a patient’s scalp, with or without tenderness, pruritus, or pain, we want to recognize that as possibly an early sign of central centrifugal cicatricial alopecia [CCCA],” she said. “We want to pick up cases of CCCA forme fruste [central hair breakage] early.”
Medicated shampoos are helpful for all patients with seborrheic dermatitis. This notion is more complicated. “In theory, medicated shampoos like ketoconazole should be helpful, but if the shampoos are too drying for the hair and they cause further hair breakage, that’s going to be a problem as well,” explained Dr. Heath, who was the senior author of an article on how to address common conditions affecting pediatric and adolescent patients with skin of color. For patients with tightly coiled hair, she recommends applying antifungal shampoos to the scalp only, waiting 5-10 minutes, rinsing, and shampooing the scalp and hair with a moisturizing shampoo and rinsing. They can then condition with a moisturizing conditioner and style their hair as desired.
Don’t touch a Black woman’s hair. That unwritten rule may apply to a woman you pass on the street, she said, but not during clinical exams in cases where clinicians and patients seeking hair loss treatment have different hair types. “Touch the hair; don’t do a lean-in exam,” emphasized Dr. Heath, who is the inaugural faculty scholar at Temple University Lewis Katz School of Medicine’s Office of Health Equity Diversity, and Inclusion. “You want to perform the scalp and hair exam with cultural humility.” Understanding the patient’s hair care goals and perspective allows dermatologists to take a more individualized approach to their concerns, especially in race-discordant patient-physician interactions.
Going natural (chemical-free) will solve scarring hair loss problems. This is false. “Genetic defects in the hair shaft have been described as the cause of some CCCA cases, so we need to stop solely blaming the patient for that condition,” she said. Dr. Heath noted that the transition point between natural hair and relaxed hair is highly prone to breakage. She suggests low or lower tension options such as knotless braids, and crochet hairstyles, and when patients have locs, they should be shoulder length or higher to reduce tension.
Dr. Heath disclosed that she has served as a consultant or adviser for Arcutis, CeraVe, Janssen Pharmaceuticals, Johnson & Johnson Pharmaceutical Research & Development, Leo, Lilly, Pfizer, and Regeneron Pharmaceuticals.
Medscape and this news organization are owned by the same parent company.
HONOLULU –
“This is false,” Dr. Heath, director of pediatric dermatology at Temple University, Philadelphia, said at the Hawaii Dermatology Seminar provided by MedscapeLIVE! With little manipulation, length may be retained, since tightly coiled hair has a higher likelihood of breakage, she said. “But washing the scalp and hair is recommended for tightly coiled hair weekly or every other week. Exclusively co-washing – a technique where hair conditioner is used instead of shampooing – is also not advised due to scalp build-up.”
Other myths she addressed include the following:
“I have a weak spot (or stress spot) on the top of my scalp.” These terms may be used to describe hair on a spot that goes through cycles of breaking off and re-growing. This is false. “If someone were to say that, and we see short hairs on the top of a patient’s scalp, with or without tenderness, pruritus, or pain, we want to recognize that as possibly an early sign of central centrifugal cicatricial alopecia [CCCA],” she said. “We want to pick up cases of CCCA forme fruste [central hair breakage] early.”
Medicated shampoos are helpful for all patients with seborrheic dermatitis. This notion is more complicated. “In theory, medicated shampoos like ketoconazole should be helpful, but if the shampoos are too drying for the hair and they cause further hair breakage, that’s going to be a problem as well,” explained Dr. Heath, who was the senior author of an article on how to address common conditions affecting pediatric and adolescent patients with skin of color. For patients with tightly coiled hair, she recommends applying antifungal shampoos to the scalp only, waiting 5-10 minutes, rinsing, and shampooing the scalp and hair with a moisturizing shampoo and rinsing. They can then condition with a moisturizing conditioner and style their hair as desired.
Don’t touch a Black woman’s hair. That unwritten rule may apply to a woman you pass on the street, she said, but not during clinical exams in cases where clinicians and patients seeking hair loss treatment have different hair types. “Touch the hair; don’t do a lean-in exam,” emphasized Dr. Heath, who is the inaugural faculty scholar at Temple University Lewis Katz School of Medicine’s Office of Health Equity Diversity, and Inclusion. “You want to perform the scalp and hair exam with cultural humility.” Understanding the patient’s hair care goals and perspective allows dermatologists to take a more individualized approach to their concerns, especially in race-discordant patient-physician interactions.
Going natural (chemical-free) will solve scarring hair loss problems. This is false. “Genetic defects in the hair shaft have been described as the cause of some CCCA cases, so we need to stop solely blaming the patient for that condition,” she said. Dr. Heath noted that the transition point between natural hair and relaxed hair is highly prone to breakage. She suggests low or lower tension options such as knotless braids, and crochet hairstyles, and when patients have locs, they should be shoulder length or higher to reduce tension.
Dr. Heath disclosed that she has served as a consultant or adviser for Arcutis, CeraVe, Janssen Pharmaceuticals, Johnson & Johnson Pharmaceutical Research & Development, Leo, Lilly, Pfizer, and Regeneron Pharmaceuticals.
Medscape and this news organization are owned by the same parent company.
AT THE MEDSCAPE LIVE! HAWAII DERMATOLOGY SEMINAR