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‘Frame running’ may help boost physical activity in MS
MILAN – , a pilot study suggests.
“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.
Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.
“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.
It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Dearth of exercise opportunities
The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.
This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”
In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.
The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.
The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.
The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
The camaraderie of physical activity
With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.
The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).
There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.
A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.
The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
Mix of physical interventions
Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.
He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”
However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”
With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”
Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.
Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”
The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MILAN – , a pilot study suggests.
“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.
Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.
“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.
It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Dearth of exercise opportunities
The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.
This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”
In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.
The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.
The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.
The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
The camaraderie of physical activity
With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.
The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).
There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.
A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.
The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
Mix of physical interventions
Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.
He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”
However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”
With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”
Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.
Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”
The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MILAN – , a pilot study suggests.
“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.
Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.
“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.
It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Dearth of exercise opportunities
The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.
This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”
In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.
The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.
The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.
The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
The camaraderie of physical activity
With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.
The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).
There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.
A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.
The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
Mix of physical interventions
Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.
He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”
However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”
With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”
Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.
Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”
The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2023
MS, DMTs, and pregnancy: Beware of over-caution regarding treatment
MILAN – The news about multiple sclerosis (MS) and child-bearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.
Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication – or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.
Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.
While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”
But some treatments may be harmful to the fetus, she said. Teriflunomide must be stopped before pregnancy. Natalizumab and fingolimod-siponimod raise the risk of rebound, and alternate drugs should be considered before pregnancy. However, anti–CD 20 drugs and cladribine “may be a relevant option because their use before pregnancy may provide effective disease control without exposing the fetus or the baby.”
Should women be on MS drugs at all during pregnancy, a period when MS typically wanes? “The recommendation is to discontinue disease-modifying therapy before conception,” Dr. Leray said. “However, we know now that some DMTs can be used safely during pregnancy, especially injectables.” Specifically, beta interferon and glatiramer acetate can be used safely during pregnancy, she said.
The biggest hurdle comes after pregnancy, when women face a high risk of MS rebound. The relapse rate has fallen in recent years from about 30% to 11%-14%, Dr. Leray said, possibly because of the rise of more effective treatment. But the risk, she said, is still significant.
What can clinicians do to avert relapse? According to Dr. Leray, research has failed to support several possible alternatives to DMTs – high-dose corticosteroids, intravenous immunoglobulin, and hormonal treatment. “There was no evidence of efficacy of any of these strategies, both in randomized clinical trials and in real-world studies.”
For now, it seems best to restart DMTs as soon as possible after delivery, Dr. Leray said. She urged colleagues to keep in mind that it takes about 3 months for DMTs to reach full efficacy – and research suggests the highest risk of relapse is during the first 3 months after delivery. “That has to be taken into account in the therapeutic strategy,” she said.
Dr. Leray reports consulting/lecture/travel grants from Biogen, Genzyme, MedDay, Merck, Novartis, and Roche.
MILAN – The news about multiple sclerosis (MS) and child-bearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.
Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication – or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.
Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.
While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”
But some treatments may be harmful to the fetus, she said. Teriflunomide must be stopped before pregnancy. Natalizumab and fingolimod-siponimod raise the risk of rebound, and alternate drugs should be considered before pregnancy. However, anti–CD 20 drugs and cladribine “may be a relevant option because their use before pregnancy may provide effective disease control without exposing the fetus or the baby.”
Should women be on MS drugs at all during pregnancy, a period when MS typically wanes? “The recommendation is to discontinue disease-modifying therapy before conception,” Dr. Leray said. “However, we know now that some DMTs can be used safely during pregnancy, especially injectables.” Specifically, beta interferon and glatiramer acetate can be used safely during pregnancy, she said.
The biggest hurdle comes after pregnancy, when women face a high risk of MS rebound. The relapse rate has fallen in recent years from about 30% to 11%-14%, Dr. Leray said, possibly because of the rise of more effective treatment. But the risk, she said, is still significant.
What can clinicians do to avert relapse? According to Dr. Leray, research has failed to support several possible alternatives to DMTs – high-dose corticosteroids, intravenous immunoglobulin, and hormonal treatment. “There was no evidence of efficacy of any of these strategies, both in randomized clinical trials and in real-world studies.”
For now, it seems best to restart DMTs as soon as possible after delivery, Dr. Leray said. She urged colleagues to keep in mind that it takes about 3 months for DMTs to reach full efficacy – and research suggests the highest risk of relapse is during the first 3 months after delivery. “That has to be taken into account in the therapeutic strategy,” she said.
Dr. Leray reports consulting/lecture/travel grants from Biogen, Genzyme, MedDay, Merck, Novartis, and Roche.
MILAN – The news about multiple sclerosis (MS) and child-bearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.
Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication – or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.
Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.
While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”
But some treatments may be harmful to the fetus, she said. Teriflunomide must be stopped before pregnancy. Natalizumab and fingolimod-siponimod raise the risk of rebound, and alternate drugs should be considered before pregnancy. However, anti–CD 20 drugs and cladribine “may be a relevant option because their use before pregnancy may provide effective disease control without exposing the fetus or the baby.”
Should women be on MS drugs at all during pregnancy, a period when MS typically wanes? “The recommendation is to discontinue disease-modifying therapy before conception,” Dr. Leray said. “However, we know now that some DMTs can be used safely during pregnancy, especially injectables.” Specifically, beta interferon and glatiramer acetate can be used safely during pregnancy, she said.
The biggest hurdle comes after pregnancy, when women face a high risk of MS rebound. The relapse rate has fallen in recent years from about 30% to 11%-14%, Dr. Leray said, possibly because of the rise of more effective treatment. But the risk, she said, is still significant.
What can clinicians do to avert relapse? According to Dr. Leray, research has failed to support several possible alternatives to DMTs – high-dose corticosteroids, intravenous immunoglobulin, and hormonal treatment. “There was no evidence of efficacy of any of these strategies, both in randomized clinical trials and in real-world studies.”
For now, it seems best to restart DMTs as soon as possible after delivery, Dr. Leray said. She urged colleagues to keep in mind that it takes about 3 months for DMTs to reach full efficacy – and research suggests the highest risk of relapse is during the first 3 months after delivery. “That has to be taken into account in the therapeutic strategy,” she said.
Dr. Leray reports consulting/lecture/travel grants from Biogen, Genzyme, MedDay, Merck, Novartis, and Roche.
AT ECTRIMS 2023
Wearable devices show promise in monitoring multiple sclerosis
MILAN – , suggests a pilot study.
Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.
The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.
Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Leveraging big data to improve outcomes
The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.
For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.
Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.
To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.
This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
Feasible with high levels of confidence
Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.
The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.
The team reports that the data from the tool kit “are in line with those reported in the literature.”
It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.
Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.
The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.
Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.
They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
Reducing daily step count
Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”
She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.
“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”
The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
MILAN – , suggests a pilot study.
Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.
The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.
Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Leveraging big data to improve outcomes
The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.
For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.
Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.
To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.
This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
Feasible with high levels of confidence
Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.
The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.
The team reports that the data from the tool kit “are in line with those reported in the literature.”
It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.
Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.
The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.
Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.
They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
Reducing daily step count
Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”
She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.
“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”
The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
MILAN – , suggests a pilot study.
Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.
The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.
Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Leveraging big data to improve outcomes
The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.
For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.
Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.
To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.
This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
Feasible with high levels of confidence
Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.
The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.
The team reports that the data from the tool kit “are in line with those reported in the literature.”
It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.
Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.
The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.
Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.
They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
Reducing daily step count
Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”
She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.
“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”
The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
NMO: Study says double diagnoses with MS are common
MILAN – , according to a poster presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
“There is a lack of education in differentiating between MS and NMO even in the medical community, which may result in a high misdiagnosis rate,” said study lead author Ka-Ho Wong, MBA, of the University of Utah, Salt Lake City, in an interview.
“NMO was recognized in the late 1800s and was historically thought to be a variant of MS until 1999,” said Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, both in Boston, in an interview.
“They are both relapsing inflammatory disorders of the central nervous system with similarities in symptoms of weakness, numbness, mobility problem, vision defects, pain and fatigue,” said Dr. Levy, who did not take part in the new study. “A blood test for NMO was developed in 2004 and improved over time to the point that it can now reliably distinguish NMO from MS.”
As for therapy, “recent research has confirmed the two conditions are immunologically different and respond to different treatment,” Dr. Levy said. “The treatments developed for MS, especially from the 1990s, are harmful in NMO so it is important to make the diagnosis correctly.”
He added that “we do not recognize overlap between NMO or MS – it’s one or the other.”
Exploring the reasons for misdiagnosis
Mr. Wong, the present study’s lead author, said he and a research team launched the new study to better understand who gets misdiagnosed. “We know that almost 50% of the individuals get misdiagnosed at some point. However, what we don’t know yet is if the influencing factors are social determinants of health or if there are other causes.”
For the study, Mr. Wong and colleagues analyzed data from TriNetX, a health research network with access to medical records from 61 U.S. health care organizations. providing access to electronic medical records that includes sixty-one health care organizations (HCOs) in the United States.
ICD-10 coding statistics from 2008 to 2022 identified 7,657 patients with diagnoses for NMO. Of those, 4,040 (53%) only had diagnoses for NMO, and the rest (3,617, 47%) had diagnoses for both NMO and MS.
The researchers focused on 1,265 patients who had been coded for both diagnoses and had at least three clinical visits. They determined that a patient was misdiagnosed when they had three consecutive diagnoses of the same type. “For example, if they had MS but got misdiagnosed as NMO, once they are confirmed as MS they must have three or more consecutive diagnosis of MS to be considered as misdiagnosed,” Mr. Wong said.
Of the 1,265 subjects, the researchers determined that 308 (24%) had NMO but had been misdiagnosed as having MS, 189 (15%) had MS but were misdiagnosed as having NMO, and 768 (61%) were interchangeably diagnosed with the two conditions over time.
Among these three groups, 70.8%, 73.1%, and 78.4% were female, respectively; and 59.4%, 52.9%, and 53.0% were White, respectively. The percentages of Black patients were 17.2%, 24.3%, and 28.9%, respectively. Information about statistical significance was not provided in the poster.
Dr. Levy said he would “expect most NMO patients to initially be diagnosed with MS. It’s unusual to start with a diagnosis of NMO and then figure out it’s MS.”
As for the larger number of people with interchangeable diagnoses, Dr. Levy said that likely “reflects the messiness of billing codes.” For his part, Mr. Wong said there could be multiple causes for the interchangeable diagnoses: lack of disease knowledge, miscoding, lack of Food and Drug Administration–approved treatment for NMO at the time, and potentially other factors.
What does it all mean?
As for the study’s significance, Mr. Wong said a full workup should be performed before diagnosis, “and a neurologist should never prescribe disease-modifying therapies prior to a confirmation of diagnosis.”
Indeed, some disease-modifying therapies for MS are inappropriate for patients with NMO, Dr. Levy said. “The older medications, including beta-interferons, are among the most harmful to NMO patients. But they are not commonly used as first line for MS as they used to be. In contrast, B cell–depleting medications like ocrelizumab may be helpful in NMO.”
In regards to diagnosis, Dr. Levy noted that the NMO aquaporin-4 (AQP4) antibody test is “extremely specific and reliable.”
“A positive test result in the context of a clinical presentation of central nervous system inflammation allows for the diagnosis of NMO,” he said. “A negative test result is more complicated and may require some expertise to sort out after a careful review of the history, neurological exam, MRI features, central nervous system testing and other blood test results.”
The study was funded by the Sumaira Foundation. The authors did not provide information about relevant disclosures. Dr. Levy reports personal compensation for advisory board activities from Roche, Genentech, Chugai, Horizon, Alexion and Mitsubishi and grant support from Genentech, Horizon, Alexion, Sanofi, and UCB.
MILAN – , according to a poster presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
“There is a lack of education in differentiating between MS and NMO even in the medical community, which may result in a high misdiagnosis rate,” said study lead author Ka-Ho Wong, MBA, of the University of Utah, Salt Lake City, in an interview.
“NMO was recognized in the late 1800s and was historically thought to be a variant of MS until 1999,” said Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, both in Boston, in an interview.
“They are both relapsing inflammatory disorders of the central nervous system with similarities in symptoms of weakness, numbness, mobility problem, vision defects, pain and fatigue,” said Dr. Levy, who did not take part in the new study. “A blood test for NMO was developed in 2004 and improved over time to the point that it can now reliably distinguish NMO from MS.”
As for therapy, “recent research has confirmed the two conditions are immunologically different and respond to different treatment,” Dr. Levy said. “The treatments developed for MS, especially from the 1990s, are harmful in NMO so it is important to make the diagnosis correctly.”
He added that “we do not recognize overlap between NMO or MS – it’s one or the other.”
Exploring the reasons for misdiagnosis
Mr. Wong, the present study’s lead author, said he and a research team launched the new study to better understand who gets misdiagnosed. “We know that almost 50% of the individuals get misdiagnosed at some point. However, what we don’t know yet is if the influencing factors are social determinants of health or if there are other causes.”
For the study, Mr. Wong and colleagues analyzed data from TriNetX, a health research network with access to medical records from 61 U.S. health care organizations. providing access to electronic medical records that includes sixty-one health care organizations (HCOs) in the United States.
ICD-10 coding statistics from 2008 to 2022 identified 7,657 patients with diagnoses for NMO. Of those, 4,040 (53%) only had diagnoses for NMO, and the rest (3,617, 47%) had diagnoses for both NMO and MS.
The researchers focused on 1,265 patients who had been coded for both diagnoses and had at least three clinical visits. They determined that a patient was misdiagnosed when they had three consecutive diagnoses of the same type. “For example, if they had MS but got misdiagnosed as NMO, once they are confirmed as MS they must have three or more consecutive diagnosis of MS to be considered as misdiagnosed,” Mr. Wong said.
Of the 1,265 subjects, the researchers determined that 308 (24%) had NMO but had been misdiagnosed as having MS, 189 (15%) had MS but were misdiagnosed as having NMO, and 768 (61%) were interchangeably diagnosed with the two conditions over time.
Among these three groups, 70.8%, 73.1%, and 78.4% were female, respectively; and 59.4%, 52.9%, and 53.0% were White, respectively. The percentages of Black patients were 17.2%, 24.3%, and 28.9%, respectively. Information about statistical significance was not provided in the poster.
Dr. Levy said he would “expect most NMO patients to initially be diagnosed with MS. It’s unusual to start with a diagnosis of NMO and then figure out it’s MS.”
As for the larger number of people with interchangeable diagnoses, Dr. Levy said that likely “reflects the messiness of billing codes.” For his part, Mr. Wong said there could be multiple causes for the interchangeable diagnoses: lack of disease knowledge, miscoding, lack of Food and Drug Administration–approved treatment for NMO at the time, and potentially other factors.
What does it all mean?
As for the study’s significance, Mr. Wong said a full workup should be performed before diagnosis, “and a neurologist should never prescribe disease-modifying therapies prior to a confirmation of diagnosis.”
Indeed, some disease-modifying therapies for MS are inappropriate for patients with NMO, Dr. Levy said. “The older medications, including beta-interferons, are among the most harmful to NMO patients. But they are not commonly used as first line for MS as they used to be. In contrast, B cell–depleting medications like ocrelizumab may be helpful in NMO.”
In regards to diagnosis, Dr. Levy noted that the NMO aquaporin-4 (AQP4) antibody test is “extremely specific and reliable.”
“A positive test result in the context of a clinical presentation of central nervous system inflammation allows for the diagnosis of NMO,” he said. “A negative test result is more complicated and may require some expertise to sort out after a careful review of the history, neurological exam, MRI features, central nervous system testing and other blood test results.”
The study was funded by the Sumaira Foundation. The authors did not provide information about relevant disclosures. Dr. Levy reports personal compensation for advisory board activities from Roche, Genentech, Chugai, Horizon, Alexion and Mitsubishi and grant support from Genentech, Horizon, Alexion, Sanofi, and UCB.
MILAN – , according to a poster presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
“There is a lack of education in differentiating between MS and NMO even in the medical community, which may result in a high misdiagnosis rate,” said study lead author Ka-Ho Wong, MBA, of the University of Utah, Salt Lake City, in an interview.
“NMO was recognized in the late 1800s and was historically thought to be a variant of MS until 1999,” said Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, both in Boston, in an interview.
“They are both relapsing inflammatory disorders of the central nervous system with similarities in symptoms of weakness, numbness, mobility problem, vision defects, pain and fatigue,” said Dr. Levy, who did not take part in the new study. “A blood test for NMO was developed in 2004 and improved over time to the point that it can now reliably distinguish NMO from MS.”
As for therapy, “recent research has confirmed the two conditions are immunologically different and respond to different treatment,” Dr. Levy said. “The treatments developed for MS, especially from the 1990s, are harmful in NMO so it is important to make the diagnosis correctly.”
He added that “we do not recognize overlap between NMO or MS – it’s one or the other.”
Exploring the reasons for misdiagnosis
Mr. Wong, the present study’s lead author, said he and a research team launched the new study to better understand who gets misdiagnosed. “We know that almost 50% of the individuals get misdiagnosed at some point. However, what we don’t know yet is if the influencing factors are social determinants of health or if there are other causes.”
For the study, Mr. Wong and colleagues analyzed data from TriNetX, a health research network with access to medical records from 61 U.S. health care organizations. providing access to electronic medical records that includes sixty-one health care organizations (HCOs) in the United States.
ICD-10 coding statistics from 2008 to 2022 identified 7,657 patients with diagnoses for NMO. Of those, 4,040 (53%) only had diagnoses for NMO, and the rest (3,617, 47%) had diagnoses for both NMO and MS.
The researchers focused on 1,265 patients who had been coded for both diagnoses and had at least three clinical visits. They determined that a patient was misdiagnosed when they had three consecutive diagnoses of the same type. “For example, if they had MS but got misdiagnosed as NMO, once they are confirmed as MS they must have three or more consecutive diagnosis of MS to be considered as misdiagnosed,” Mr. Wong said.
Of the 1,265 subjects, the researchers determined that 308 (24%) had NMO but had been misdiagnosed as having MS, 189 (15%) had MS but were misdiagnosed as having NMO, and 768 (61%) were interchangeably diagnosed with the two conditions over time.
Among these three groups, 70.8%, 73.1%, and 78.4% were female, respectively; and 59.4%, 52.9%, and 53.0% were White, respectively. The percentages of Black patients were 17.2%, 24.3%, and 28.9%, respectively. Information about statistical significance was not provided in the poster.
Dr. Levy said he would “expect most NMO patients to initially be diagnosed with MS. It’s unusual to start with a diagnosis of NMO and then figure out it’s MS.”
As for the larger number of people with interchangeable diagnoses, Dr. Levy said that likely “reflects the messiness of billing codes.” For his part, Mr. Wong said there could be multiple causes for the interchangeable diagnoses: lack of disease knowledge, miscoding, lack of Food and Drug Administration–approved treatment for NMO at the time, and potentially other factors.
What does it all mean?
As for the study’s significance, Mr. Wong said a full workup should be performed before diagnosis, “and a neurologist should never prescribe disease-modifying therapies prior to a confirmation of diagnosis.”
Indeed, some disease-modifying therapies for MS are inappropriate for patients with NMO, Dr. Levy said. “The older medications, including beta-interferons, are among the most harmful to NMO patients. But they are not commonly used as first line for MS as they used to be. In contrast, B cell–depleting medications like ocrelizumab may be helpful in NMO.”
In regards to diagnosis, Dr. Levy noted that the NMO aquaporin-4 (AQP4) antibody test is “extremely specific and reliable.”
“A positive test result in the context of a clinical presentation of central nervous system inflammation allows for the diagnosis of NMO,” he said. “A negative test result is more complicated and may require some expertise to sort out after a careful review of the history, neurological exam, MRI features, central nervous system testing and other blood test results.”
The study was funded by the Sumaira Foundation. The authors did not provide information about relevant disclosures. Dr. Levy reports personal compensation for advisory board activities from Roche, Genentech, Chugai, Horizon, Alexion and Mitsubishi and grant support from Genentech, Horizon, Alexion, Sanofi, and UCB.
AT ECTRIMS 2023
EBV and MS: Just how deep is the link?
MILAN – in a joint presentation at the 9th Joint ECTRIMS-ACTRIMS meeting.
Armed with the findings of his own landmark 2022 study into EBV and MS, Harvard Medical School, Boston, professor of medicine Alberto Ascherio, MD, DrPH, argued that they’re tightly connected. But rheumatologist William H. Robinson, MD, PhD, of Stanford (Calif.) University, said that while he also believes EBV plays a significant role in MS, “there’s likely a role for a second hit” – some other factor. “Why are 95% of us EBV-infected, but only a small subset ultimately develop MS or ... other autoimmune diseases?”
As a 2023 review noted, researchers have puzzled over the connection between EBV and MS since the early 1980s. “Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS.” But it’s not clear how EBV – which strikes more than an estimated 95% of humans and causes mononucleosis – manages to trigger MS.
A rare complication of EBV infection
In the 2022 study, Dr. Ascherio aimed to understand exactly how deeply EBV and MS are connected by analyzing serum data gathered from more than 10 million active-duty members of the U.S. military. Of those, 955 were diagnosed with MS.
The researchers focused on 801 subjects with MS and matched them to 1,566 controls. Only 1 of the 801 subjects with MS had a negative EBV test prior to diagnosis, a fact that researchers believe could be due to a factor such as a failure to seroconvert during infection. “At baseline, 35 MS cases and 107 controls were EBV-negative,” the study reported. “All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up.”
Overall, subjects who were positive for EBV were 32.4 times to develop MS than those who weren’t (95% confidence interval, 4.3-245.3; P < 0.001).
Is it possible that immune dysregulation from MS precedes EBV infection? The researchers analyzed viruses in 30 subjects with MS – before and after MS onset – and in 30 controls. The findings suggested that EBV was the major player, Dr. Ascherio said.
Researchers also focused on cytomegalovirus (CMV) infection, which is closely related to EBV and to the chicken pox virus. “CMV seroconversion is not associated with MS, and positivity for CMV at baseline was associated with a modestly lower risk of MS,” Dr. Ascherio said.
In the big picture, “this data establishes beyond reasonable doubt that MS is a rare complication of EBV infection,” Dr. Ascherio said. “The main question now is whether the virus triggers an immune process that then is self-maintained, or whether the presence of the infection keeps feeding the immune process.”
Inadequate evidence for causation
In his presentation, Dr. Robinson asked: “Does EBV cause MS? Really? All of MS? In humans [with MS], yes, we found monoclonal antibodies expressed by the B cells that bound to EBV. But we also found spinal fluid B cells and coding antibodies that bound to multiple other viruses, including rubella, VZV [varicella-zoster virus/chickenpox], CMV, and HSV [herpes simplex virus]. And there’s even a measles reactive antibody there.”
And there’s evidence that human herpes virus type 6 (HHV-6) and HHV-6A could be linked to MS: “Maybe HHV-6 or HHV-6A is the cause of MS in a subset of patients,” Dr. Robinson said. Research suggests that pox viruses could be another possible cause, he said.
He added: “I’m a rheumatologist, and I see patients in the clinic and in the hospital who have lupus, a disease highly associated with EBV infection. But they definitely do not have MS, nor do they have RA [rheumatoid arthritis], and likewise your MS patients don’t have lupus. What’s up with all these diseases potentially being linked to EBV?”
A missing piece of the puzzle?
In a discussion period, Dr. Ascherio responded to Dr. Robinson by saying he’s waiting to see evidence that patients with the other diseases linked to EBV don’t develop them if they’re EBV-negative. Dr. Ascherio added that it’s possible that there are different strains of EBV, and some may be more likely to cause MS.
What does this all mean for MS prevention? In a commentary published with Dr. Ascherio’s 2022 study, Dr. Robinson and a coauthor asked: “Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease? Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”
Dr. Ascherio discloses speaker/consultant relationships with Prada Foundation, WebMD, Biogen, Moderna, Merck, Roche, and GSK. Dr. Robinson discloses unspecified relationships with Altreca and Flatiron Bio, and he is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV.
MILAN – in a joint presentation at the 9th Joint ECTRIMS-ACTRIMS meeting.
Armed with the findings of his own landmark 2022 study into EBV and MS, Harvard Medical School, Boston, professor of medicine Alberto Ascherio, MD, DrPH, argued that they’re tightly connected. But rheumatologist William H. Robinson, MD, PhD, of Stanford (Calif.) University, said that while he also believes EBV plays a significant role in MS, “there’s likely a role for a second hit” – some other factor. “Why are 95% of us EBV-infected, but only a small subset ultimately develop MS or ... other autoimmune diseases?”
As a 2023 review noted, researchers have puzzled over the connection between EBV and MS since the early 1980s. “Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS.” But it’s not clear how EBV – which strikes more than an estimated 95% of humans and causes mononucleosis – manages to trigger MS.
A rare complication of EBV infection
In the 2022 study, Dr. Ascherio aimed to understand exactly how deeply EBV and MS are connected by analyzing serum data gathered from more than 10 million active-duty members of the U.S. military. Of those, 955 were diagnosed with MS.
The researchers focused on 801 subjects with MS and matched them to 1,566 controls. Only 1 of the 801 subjects with MS had a negative EBV test prior to diagnosis, a fact that researchers believe could be due to a factor such as a failure to seroconvert during infection. “At baseline, 35 MS cases and 107 controls were EBV-negative,” the study reported. “All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up.”
Overall, subjects who were positive for EBV were 32.4 times to develop MS than those who weren’t (95% confidence interval, 4.3-245.3; P < 0.001).
Is it possible that immune dysregulation from MS precedes EBV infection? The researchers analyzed viruses in 30 subjects with MS – before and after MS onset – and in 30 controls. The findings suggested that EBV was the major player, Dr. Ascherio said.
Researchers also focused on cytomegalovirus (CMV) infection, which is closely related to EBV and to the chicken pox virus. “CMV seroconversion is not associated with MS, and positivity for CMV at baseline was associated with a modestly lower risk of MS,” Dr. Ascherio said.
In the big picture, “this data establishes beyond reasonable doubt that MS is a rare complication of EBV infection,” Dr. Ascherio said. “The main question now is whether the virus triggers an immune process that then is self-maintained, or whether the presence of the infection keeps feeding the immune process.”
Inadequate evidence for causation
In his presentation, Dr. Robinson asked: “Does EBV cause MS? Really? All of MS? In humans [with MS], yes, we found monoclonal antibodies expressed by the B cells that bound to EBV. But we also found spinal fluid B cells and coding antibodies that bound to multiple other viruses, including rubella, VZV [varicella-zoster virus/chickenpox], CMV, and HSV [herpes simplex virus]. And there’s even a measles reactive antibody there.”
And there’s evidence that human herpes virus type 6 (HHV-6) and HHV-6A could be linked to MS: “Maybe HHV-6 or HHV-6A is the cause of MS in a subset of patients,” Dr. Robinson said. Research suggests that pox viruses could be another possible cause, he said.
He added: “I’m a rheumatologist, and I see patients in the clinic and in the hospital who have lupus, a disease highly associated with EBV infection. But they definitely do not have MS, nor do they have RA [rheumatoid arthritis], and likewise your MS patients don’t have lupus. What’s up with all these diseases potentially being linked to EBV?”
A missing piece of the puzzle?
In a discussion period, Dr. Ascherio responded to Dr. Robinson by saying he’s waiting to see evidence that patients with the other diseases linked to EBV don’t develop them if they’re EBV-negative. Dr. Ascherio added that it’s possible that there are different strains of EBV, and some may be more likely to cause MS.
What does this all mean for MS prevention? In a commentary published with Dr. Ascherio’s 2022 study, Dr. Robinson and a coauthor asked: “Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease? Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”
Dr. Ascherio discloses speaker/consultant relationships with Prada Foundation, WebMD, Biogen, Moderna, Merck, Roche, and GSK. Dr. Robinson discloses unspecified relationships with Altreca and Flatiron Bio, and he is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV.
MILAN – in a joint presentation at the 9th Joint ECTRIMS-ACTRIMS meeting.
Armed with the findings of his own landmark 2022 study into EBV and MS, Harvard Medical School, Boston, professor of medicine Alberto Ascherio, MD, DrPH, argued that they’re tightly connected. But rheumatologist William H. Robinson, MD, PhD, of Stanford (Calif.) University, said that while he also believes EBV plays a significant role in MS, “there’s likely a role for a second hit” – some other factor. “Why are 95% of us EBV-infected, but only a small subset ultimately develop MS or ... other autoimmune diseases?”
As a 2023 review noted, researchers have puzzled over the connection between EBV and MS since the early 1980s. “Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS.” But it’s not clear how EBV – which strikes more than an estimated 95% of humans and causes mononucleosis – manages to trigger MS.
A rare complication of EBV infection
In the 2022 study, Dr. Ascherio aimed to understand exactly how deeply EBV and MS are connected by analyzing serum data gathered from more than 10 million active-duty members of the U.S. military. Of those, 955 were diagnosed with MS.
The researchers focused on 801 subjects with MS and matched them to 1,566 controls. Only 1 of the 801 subjects with MS had a negative EBV test prior to diagnosis, a fact that researchers believe could be due to a factor such as a failure to seroconvert during infection. “At baseline, 35 MS cases and 107 controls were EBV-negative,” the study reported. “All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up.”
Overall, subjects who were positive for EBV were 32.4 times to develop MS than those who weren’t (95% confidence interval, 4.3-245.3; P < 0.001).
Is it possible that immune dysregulation from MS precedes EBV infection? The researchers analyzed viruses in 30 subjects with MS – before and after MS onset – and in 30 controls. The findings suggested that EBV was the major player, Dr. Ascherio said.
Researchers also focused on cytomegalovirus (CMV) infection, which is closely related to EBV and to the chicken pox virus. “CMV seroconversion is not associated with MS, and positivity for CMV at baseline was associated with a modestly lower risk of MS,” Dr. Ascherio said.
In the big picture, “this data establishes beyond reasonable doubt that MS is a rare complication of EBV infection,” Dr. Ascherio said. “The main question now is whether the virus triggers an immune process that then is self-maintained, or whether the presence of the infection keeps feeding the immune process.”
Inadequate evidence for causation
In his presentation, Dr. Robinson asked: “Does EBV cause MS? Really? All of MS? In humans [with MS], yes, we found monoclonal antibodies expressed by the B cells that bound to EBV. But we also found spinal fluid B cells and coding antibodies that bound to multiple other viruses, including rubella, VZV [varicella-zoster virus/chickenpox], CMV, and HSV [herpes simplex virus]. And there’s even a measles reactive antibody there.”
And there’s evidence that human herpes virus type 6 (HHV-6) and HHV-6A could be linked to MS: “Maybe HHV-6 or HHV-6A is the cause of MS in a subset of patients,” Dr. Robinson said. Research suggests that pox viruses could be another possible cause, he said.
He added: “I’m a rheumatologist, and I see patients in the clinic and in the hospital who have lupus, a disease highly associated with EBV infection. But they definitely do not have MS, nor do they have RA [rheumatoid arthritis], and likewise your MS patients don’t have lupus. What’s up with all these diseases potentially being linked to EBV?”
A missing piece of the puzzle?
In a discussion period, Dr. Ascherio responded to Dr. Robinson by saying he’s waiting to see evidence that patients with the other diseases linked to EBV don’t develop them if they’re EBV-negative. Dr. Ascherio added that it’s possible that there are different strains of EBV, and some may be more likely to cause MS.
What does this all mean for MS prevention? In a commentary published with Dr. Ascherio’s 2022 study, Dr. Robinson and a coauthor asked: “Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease? Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”
Dr. Ascherio discloses speaker/consultant relationships with Prada Foundation, WebMD, Biogen, Moderna, Merck, Roche, and GSK. Dr. Robinson discloses unspecified relationships with Altreca and Flatiron Bio, and he is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV.
AT ECTRIMS 2023
Stem cell transplants in early MS: Who benefits most?
MILAN – researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.
“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).
However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”
Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”
But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”
Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.
However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”
Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.
The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.
The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.
What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”
He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”
Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”
Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.
MILAN – researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.
“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).
However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”
Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”
But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”
Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.
However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”
Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.
The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.
The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.
What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”
He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”
Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”
Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.
MILAN – researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.
“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).
However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”
Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”
But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”
Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.
However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”
Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.
The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.
The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.
What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”
He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”
Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”
Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.
AT ECTRIMS 2023
MS-tailored weight loss program achieves meaningful results
MILAN – results of a new trial show.
Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.
“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.
The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Obesity linked to MS progression
Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.
Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.
The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.
The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m2, and have a Patient-Determined Disease Steps (PDDS) score of less than 4.
The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.
Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.
The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.
Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
Significant loss in body weight
Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.
The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.
Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).
Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).
There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”
Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.
The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).
There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).
Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).
Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.
Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).
“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”
She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
Emphasizing the social side of interventions
Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”
He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”
One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.
Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”
He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”
“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.
The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.
A version of this article first appeared on Medscape.com.
MILAN – results of a new trial show.
Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.
“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.
The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Obesity linked to MS progression
Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.
Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.
The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.
The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m2, and have a Patient-Determined Disease Steps (PDDS) score of less than 4.
The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.
Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.
The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.
Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
Significant loss in body weight
Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.
The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.
Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).
Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).
There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”
Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.
The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).
There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).
Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).
Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.
Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).
“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”
She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
Emphasizing the social side of interventions
Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”
He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”
One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.
Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”
He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”
“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.
The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.
A version of this article first appeared on Medscape.com.
MILAN – results of a new trial show.
Seventy patients with MS and a high body mass index (BMI) were randomized to receive a multifaceted weight loss program or treatment as usual, resulting in almost two-thirds of the intervention group patients losing at least 5% of their body weight.
“Our weight loss intervention achieved clinically significant weight loss and improved mental quality of life,” said study presenter Sharon G. Lynch, MD, professor in the department of neurology at the University of Kansas Medical Center, Kansas City.
The results also showed weight loss “was associated with improved mobility, reduced fatigability, and improved physical quality of life.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Obesity linked to MS progression
Dr. Lynch noted that almost 40% of people with MS have comorbid obesity, and that obesity “is associated with developing MS in some studies, and also disease progression.” Moreover, MS and obesity share common chronic symptoms, particularly mobility problems, depression, fatigue, and reduced quality of life.
Despite this, no randomized controlled trials have been specifically designed to help people with MS lose weight, he noted.
The team therefore examined the efficacy of a behavioral weight loss program designed for patients with the disease, as well as the impact of weight loss on mobility and other chronic symptoms.
The participants were required to be English speaking, with access to a telephone and/or computer, and to have a confirmed diagnosis of MS. They also had to be aged 18-70 years, have a BMI of 29-50 kg/m2, and have a Patient-Determined Disease Steps (PDDS) score of less than 4.
The patients were randomly assigned to receive either a weight loss intervention or brief health education and treatment as usual. They were assessed at 6 months to measure their weight loss, mobility, and self-reported quality of life and perceived fatigability.
Dr. Lynch said the intervention was “fairly time intensive,” with an hour-long telehealth group weight loss session every week for 24 weeks, as well as monthly individual sessions for 6 months.
The participants were provided with a Fitbit activity tracker, a set of Bluetooth-enabled weighing scales, and access to the Lose It! weight loss app.
Caloric restriction was encouraged, with a focus on increasing intake of fruits and vegetables, alongside a target of 150 minutes per week of moderate to vigorous physical activity, in line with Centers for Disease Control and Prevention and American Heart Association recommendations.
Significant loss in body weight
Seventy individuals with MS took part in the trial, of whom 83% were female and 88% were White, 9% African American, and 3% Hispanic or Latino. The mean age was 46.7 years, and the mean number of years in education was 11.8.
The vast majority (96%) of the participants had relapsing remitting MS, at a mean disease duration of 10.9 years, and 82% had a score of 0 or 1 on the PDDS.
Dr. Lynch showed that participants in the intervention group lost, over the course of the study, 8.6% of their total body weight, compared with a loss of 0.7% among controls (P < .001).
Moreover, 65% of the intervention group lost at least 5% of their body weight, whereas 41% lost at least 10% of their body weight, which again was significantly higher than that seen in the control group (P < .001).
There was also a significant increase in moderate to vigorous physical activity in the intervention group as measured by accelerometry (P < .05), although Dr. Lynch pointed out this “did not necessarily correlate with their weight loss.”
Dr. Lynch showed there were significant differences across a range of anthropometric measures from baseline to follow-up between the intervention and control groups.
The adjusted difference in weight loss between the intervention and control participants was 7.8 kg, whereas the difference in reduction of BMI was 2.7 (P = .001 for both).
There was also a significant difference in the reduction in waist-to-hip ratio between the groups, at 0.033 in favor of the intervention, as well as a difference in the reduction in fat tissue, at 3.1% (P = .001 for both).
Further analyses showed weight loss was associated with significant improvements on the 6-minute walk test, at an r value of 0.48 (P = .015), and in the 25-foot walk test (r = 0.42; P = .015). Weight loss was also linked to reductions in perceived fatigability (r = 0.48; P = .005).
Dr. Lynch also reported that a 5% reduction in body weight was associated with a “clinically meaningful” improvement of 50 meters on the 6-minute walk test.
Finally, it was found the intervention was associated with a significant improvement in mental quality of life (P = .01), whereas weight loss specifically was linked to improved physical quality of life (P = .02).
“We believe that future studies should examine weight loss in people with MS who have more advanced disability,” Dr. Lynch said, and “we should examine the effects of weight loss on the underlying disease processes.”
She added they also “need to follow the patient for longer and see if they can maintain their weight loss.”
Emphasizing the social side of interventions
Session cochair Brian M. Sandroff, PhD, director of the Exercise Neurorehabilitation Research Laboratory at the Kessler Foundation, East Hanover, N.J., commented that the results are “really exciting.”
He said that the improvements across the range of measures assessed in the study were not surprising, “considering the intervention was multicomponent, and so had the potential to affect a number of different physical and cognitive domains.”
One factor in managing MS that came up again and again during the discussion at the end of the session was the social aspect of interventions, with Dr. Lynch saying the group sessions in particular were appreciated by participants in her trial.
Dr. Sandroff, who was not involved in the study, said that it has been questioned whether the social side should be controlled for when assessing interventions, or “maybe it’s something we should promote within our studies.”
He explained that being social “overcomes a lot of isolation-related issues among people with MS who have comorbidities,” which can result in “reduced quality of life and differences in symptomatic manifestations.”
“Providing that group setting might have lots of outcomes besides just a biological loss of mass” because of the intervention itself, Dr. Sandroff said.
The study was supported by grants from the National MS Society. Dr. Lynch declares relationships with Biogen, Genzyme, Teva, Sanofi, Novartis, Celgene, Roche, Immunic, National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Anokion, TG Therapeutics, and Actelion. Other authors also declared relationships. Dr. Sandroff declared no relevant relationships.
A version of this article first appeared on Medscape.com.
AT ECTRIMS 2023
‘We’re halfway home’: UCSF’s Dr. Stephen Hauser sketches MS future
MILAN – University of California, San Francisco, neurology professor Stephen Hauser, MD, told colleagues in a highlighted lecture at the 9th Joint ECTRIMS-ACTRIMS meeting.
Going forward, the MS field should emphasize identifying early biomarkers of MS, Dr. Hauser said.
He noted that many experts had anticipated “that, if we could intervene early in the relapsing phase of the disease, we would stabilize neurodegeneration and patient disability. But one of the big surprises was that that was not the case. Instead, the observed course was that by silencing relapses and focal inflammation, a clinically silent, slow, insidious progression continues during the relapsing phase of disease in patients who are not having ongoing relapses.”
Even as focal activity detected via MRI is silenced, “progression continues” he said. “This remains the great unsolved challenge.”
Dr. Hauser asked colleagues to consider a three-stage model of MS that begins with benign autoimmunity followed by pathogenic autoimmunity with subclinical tissue damage. The third stage is clinical autoimmunity.
How can you determine who’s at risk? Genetics can only fill in part of the picture because they can’t pinpoint exactly who’s likely to develop the disease. “In other autoimmune diseases, serologic autoantibodies have been by far the most effective biomarkers,” he said. “There is real-world support – not only in mice – for the concept that autoimmunity begins as a highly focused immune response that then spreads over time.”
In systemic lupus erythematosus, the cascade toward disease begins about 9 years before clinical presentation, he said. It’s 7 months in type 1 diabetes, and 20 years in rheumatoid arthritis. “These have been enormously powerful in designing both observational and therapeutic studies to try to interrupt autoimmunity at the earliest possible stage.”
What can be done if a MS biomarker is developed and shows that a person is at risk? Dr. Hauser highlighted how the anti-CD3 antibody teplizumab has been developed – and Food and Drug Administration approved – to greatly reduce the risk of type 1 diabetes in high-risk patients. Per a 2021 study, a single-14-day course of the drug was linked to lowering the risk of disease over a median 923 days by more than 50% (hazard ratio, 0.457; P < 0.01). Half of those who received the drug were free of diabetes versus just 22% of those treated by placebo.
“We’ve not yet had those serologic biomarkers in MS. But I’d like to show you that maybe we are getting close to having them,” Dr. Hauser said. He pointed to new research into a U.S. Department of Defense serum repository that’s turned up “a pretty rock-solid prediagnostic biomarker specific to MS.”
Moving on to therapy, Dr. Hauser said it’s clear that “the earlier that we treat, the more likely we are to have a large response. Highly effective therapies delivered as first-line therapies have better long-term outcomes for disability then does a graded approach that doesn’t begin with high-efficacy therapy.”
What constitutes a cure?
What else needs to be done going forward? Dr. Hauser called for the MS field to develop a definition of cure. “We should take the lead from cancer therapeutics, where they define what a cure means.” In B-cell leukemia, for example, patients are considered cured “if they remain completely disease-free in terms of clinical symptoms and biomarkers of clonal proliferation for 4 years. They have less than a 1% lifetime risk of relapse. They’re essentially cured. Our equivalent could also be developed for MS.”
He highlighted the IMPACT MS phase 4 trial, a small single-center study of ocrelizumab, which just finished enrollment and will examine the effect of the drug on treatment-naive patients at the moment of their first-ever attack. The primary endpoint is oligoclonal bands in 3 years. “I think more of these studies will probably follow,” Dr. Hauser said.
Is intervention possible at the presymptomatic stage? Targets could be members of families with multiple affected relatives who test positive for the predictive antibody signature and who have a high genetic score, he said. “We could do perhaps an Epstein-Barr virus intervention trial in this population. Then, if we have the courage and are more confident in our biomarkers, perhaps even a therapeutic trial, as has been done in these other diseases.”
As for next-generation therapies, “we’ll need to neutralize multiple cell types, especially in later disease,” he said. Bruton tyrosine kinase inhibitors “seem to be a class of drugs that was designed for the MS patient because they not only hit B cells, but also the plasmablasts that CD20s don’t hit and are the main component of the humoral pathology in chronic MS lesions.”
Dr. Hauser discloses scientific board (Accure, Alector, Annexon), board of directors (Neurona), consulting (BD, Moderna, NGM Bio), and travel reimbursement/writing support (Roche and Novartis).
MILAN – University of California, San Francisco, neurology professor Stephen Hauser, MD, told colleagues in a highlighted lecture at the 9th Joint ECTRIMS-ACTRIMS meeting.
Going forward, the MS field should emphasize identifying early biomarkers of MS, Dr. Hauser said.
He noted that many experts had anticipated “that, if we could intervene early in the relapsing phase of the disease, we would stabilize neurodegeneration and patient disability. But one of the big surprises was that that was not the case. Instead, the observed course was that by silencing relapses and focal inflammation, a clinically silent, slow, insidious progression continues during the relapsing phase of disease in patients who are not having ongoing relapses.”
Even as focal activity detected via MRI is silenced, “progression continues” he said. “This remains the great unsolved challenge.”
Dr. Hauser asked colleagues to consider a three-stage model of MS that begins with benign autoimmunity followed by pathogenic autoimmunity with subclinical tissue damage. The third stage is clinical autoimmunity.
How can you determine who’s at risk? Genetics can only fill in part of the picture because they can’t pinpoint exactly who’s likely to develop the disease. “In other autoimmune diseases, serologic autoantibodies have been by far the most effective biomarkers,” he said. “There is real-world support – not only in mice – for the concept that autoimmunity begins as a highly focused immune response that then spreads over time.”
In systemic lupus erythematosus, the cascade toward disease begins about 9 years before clinical presentation, he said. It’s 7 months in type 1 diabetes, and 20 years in rheumatoid arthritis. “These have been enormously powerful in designing both observational and therapeutic studies to try to interrupt autoimmunity at the earliest possible stage.”
What can be done if a MS biomarker is developed and shows that a person is at risk? Dr. Hauser highlighted how the anti-CD3 antibody teplizumab has been developed – and Food and Drug Administration approved – to greatly reduce the risk of type 1 diabetes in high-risk patients. Per a 2021 study, a single-14-day course of the drug was linked to lowering the risk of disease over a median 923 days by more than 50% (hazard ratio, 0.457; P < 0.01). Half of those who received the drug were free of diabetes versus just 22% of those treated by placebo.
“We’ve not yet had those serologic biomarkers in MS. But I’d like to show you that maybe we are getting close to having them,” Dr. Hauser said. He pointed to new research into a U.S. Department of Defense serum repository that’s turned up “a pretty rock-solid prediagnostic biomarker specific to MS.”
Moving on to therapy, Dr. Hauser said it’s clear that “the earlier that we treat, the more likely we are to have a large response. Highly effective therapies delivered as first-line therapies have better long-term outcomes for disability then does a graded approach that doesn’t begin with high-efficacy therapy.”
What constitutes a cure?
What else needs to be done going forward? Dr. Hauser called for the MS field to develop a definition of cure. “We should take the lead from cancer therapeutics, where they define what a cure means.” In B-cell leukemia, for example, patients are considered cured “if they remain completely disease-free in terms of clinical symptoms and biomarkers of clonal proliferation for 4 years. They have less than a 1% lifetime risk of relapse. They’re essentially cured. Our equivalent could also be developed for MS.”
He highlighted the IMPACT MS phase 4 trial, a small single-center study of ocrelizumab, which just finished enrollment and will examine the effect of the drug on treatment-naive patients at the moment of their first-ever attack. The primary endpoint is oligoclonal bands in 3 years. “I think more of these studies will probably follow,” Dr. Hauser said.
Is intervention possible at the presymptomatic stage? Targets could be members of families with multiple affected relatives who test positive for the predictive antibody signature and who have a high genetic score, he said. “We could do perhaps an Epstein-Barr virus intervention trial in this population. Then, if we have the courage and are more confident in our biomarkers, perhaps even a therapeutic trial, as has been done in these other diseases.”
As for next-generation therapies, “we’ll need to neutralize multiple cell types, especially in later disease,” he said. Bruton tyrosine kinase inhibitors “seem to be a class of drugs that was designed for the MS patient because they not only hit B cells, but also the plasmablasts that CD20s don’t hit and are the main component of the humoral pathology in chronic MS lesions.”
Dr. Hauser discloses scientific board (Accure, Alector, Annexon), board of directors (Neurona), consulting (BD, Moderna, NGM Bio), and travel reimbursement/writing support (Roche and Novartis).
MILAN – University of California, San Francisco, neurology professor Stephen Hauser, MD, told colleagues in a highlighted lecture at the 9th Joint ECTRIMS-ACTRIMS meeting.
Going forward, the MS field should emphasize identifying early biomarkers of MS, Dr. Hauser said.
He noted that many experts had anticipated “that, if we could intervene early in the relapsing phase of the disease, we would stabilize neurodegeneration and patient disability. But one of the big surprises was that that was not the case. Instead, the observed course was that by silencing relapses and focal inflammation, a clinically silent, slow, insidious progression continues during the relapsing phase of disease in patients who are not having ongoing relapses.”
Even as focal activity detected via MRI is silenced, “progression continues” he said. “This remains the great unsolved challenge.”
Dr. Hauser asked colleagues to consider a three-stage model of MS that begins with benign autoimmunity followed by pathogenic autoimmunity with subclinical tissue damage. The third stage is clinical autoimmunity.
How can you determine who’s at risk? Genetics can only fill in part of the picture because they can’t pinpoint exactly who’s likely to develop the disease. “In other autoimmune diseases, serologic autoantibodies have been by far the most effective biomarkers,” he said. “There is real-world support – not only in mice – for the concept that autoimmunity begins as a highly focused immune response that then spreads over time.”
In systemic lupus erythematosus, the cascade toward disease begins about 9 years before clinical presentation, he said. It’s 7 months in type 1 diabetes, and 20 years in rheumatoid arthritis. “These have been enormously powerful in designing both observational and therapeutic studies to try to interrupt autoimmunity at the earliest possible stage.”
What can be done if a MS biomarker is developed and shows that a person is at risk? Dr. Hauser highlighted how the anti-CD3 antibody teplizumab has been developed – and Food and Drug Administration approved – to greatly reduce the risk of type 1 diabetes in high-risk patients. Per a 2021 study, a single-14-day course of the drug was linked to lowering the risk of disease over a median 923 days by more than 50% (hazard ratio, 0.457; P < 0.01). Half of those who received the drug were free of diabetes versus just 22% of those treated by placebo.
“We’ve not yet had those serologic biomarkers in MS. But I’d like to show you that maybe we are getting close to having them,” Dr. Hauser said. He pointed to new research into a U.S. Department of Defense serum repository that’s turned up “a pretty rock-solid prediagnostic biomarker specific to MS.”
Moving on to therapy, Dr. Hauser said it’s clear that “the earlier that we treat, the more likely we are to have a large response. Highly effective therapies delivered as first-line therapies have better long-term outcomes for disability then does a graded approach that doesn’t begin with high-efficacy therapy.”
What constitutes a cure?
What else needs to be done going forward? Dr. Hauser called for the MS field to develop a definition of cure. “We should take the lead from cancer therapeutics, where they define what a cure means.” In B-cell leukemia, for example, patients are considered cured “if they remain completely disease-free in terms of clinical symptoms and biomarkers of clonal proliferation for 4 years. They have less than a 1% lifetime risk of relapse. They’re essentially cured. Our equivalent could also be developed for MS.”
He highlighted the IMPACT MS phase 4 trial, a small single-center study of ocrelizumab, which just finished enrollment and will examine the effect of the drug on treatment-naive patients at the moment of their first-ever attack. The primary endpoint is oligoclonal bands in 3 years. “I think more of these studies will probably follow,” Dr. Hauser said.
Is intervention possible at the presymptomatic stage? Targets could be members of families with multiple affected relatives who test positive for the predictive antibody signature and who have a high genetic score, he said. “We could do perhaps an Epstein-Barr virus intervention trial in this population. Then, if we have the courage and are more confident in our biomarkers, perhaps even a therapeutic trial, as has been done in these other diseases.”
As for next-generation therapies, “we’ll need to neutralize multiple cell types, especially in later disease,” he said. Bruton tyrosine kinase inhibitors “seem to be a class of drugs that was designed for the MS patient because they not only hit B cells, but also the plasmablasts that CD20s don’t hit and are the main component of the humoral pathology in chronic MS lesions.”
Dr. Hauser discloses scientific board (Accure, Alector, Annexon), board of directors (Neurona), consulting (BD, Moderna, NGM Bio), and travel reimbursement/writing support (Roche and Novartis).
AT ECTRIMS 2023
Next up in MS trials: More insight into progressive disease
MILAN – , neurologist Jeremy Chataway, MD, PhD, of University College London and Queen Square Multiple Sclerosis Center told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting.
“They’re all very different, and I think that’s exciting,” he said. “It’s a rich trial environment.”
The problem: At a median of almost 3 years in treatment for primary progressive MS, “we know that about a third of patients will progress despite on being on anti-inflammatory treatment. The same is true for secondary progressive MS. That is the hard core of what we have to think about. We want to improve the efficacy gap between control and active.”
First, Dr. Chataway highlighted the MS-STAT2 trial of simvastatin (Zocor), an inexpensive statin used to lower cholesterol. He is one of the leaders of the 3-year, multicenter, double-blind, randomized, placebo-controlled study, which is testing whether 80-mg daily doses of simvastatin will slow MS progression.
As Dr. Chataway noted, an earlier study – MS-STAT1 – found less brain atrophy in patients who took a high dose of the drug, which was “well tolerated and safe.”
Vascular morbidity drives disability and mortality in MS. “This is low-hanging fruit because we have the tools to do something about it,” he said. “There’s an opportunity here to add into our treatment paradigms across people with MS by actively treating their vascular comorbidity. It will have an effect.”
Recruitment for a trial of this approach is complete, and study results are expected in 2024 and 2025, Dr. Chataway said.
Another new study is exploring the possible effects of the antioxidant lipoic acid, also known as alpha-lipoic acid. As Dr. Chataway noted, a 2017 single-center, randomized, double-blind pilot study of daily oral 1,200 mg lipoic acid versus placebo linked the intervention to a dramatic lowering of brain atrophy – by about 50%.
The new LAPMS study, sponsored by the Veterans Administration, will explore whether lipoic acid affects walking ability, clinical outcome, and brain atrophy, Dr. Chataway said. Results from phase 2 are expected in a year or two, he said.
Dr. Chataway also highlighted one of his own trials, the OCTOPUS study, a multiarm, multistage study that will examine multiple drugs to treat progressive MS. It’s starting with metformin and will look at lipoic acid too, he said.
He also noted the phase 2 CALLIPER trial, which has completed enrollment and expects to provide top-line data in 2025. The multicenter, randomized, double-blind, placebo-controlled will test vidofludimus calcium in patients with progressive MS.
Finally, Dr. Chataway highlighted the randomized, double-blind, placebo-controlled, add-on phase 2 NACPMS trial of n-acetyl cysteine and the phase 1 randomized, double-blind, placebo-controlled trial of SAR443820, a central nervous system penetrant oral RIPK1 inhibitor.
Dr. Chataway discloses grants (UK Multiple Sclerosis Society, National Multiple Sclerosis Society, Efficacy and Mechanism Evaluation Board, Health Technology Assessment, Multiple Sclerosis Trials Collaboration, and Rosetrees Trust), advisory board service (Azadyne, Biogen, Lucid, Janssen, Merck, NervGen, Novartis, and Roche), other support (National Institute of Health Research Support, University College London Hospitals Biomedical Research Centers funding scheme), and serving as an trial investigator (Canadian MS Society, Ionis, Novartis, and Roche).
MILAN – , neurologist Jeremy Chataway, MD, PhD, of University College London and Queen Square Multiple Sclerosis Center told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting.
“They’re all very different, and I think that’s exciting,” he said. “It’s a rich trial environment.”
The problem: At a median of almost 3 years in treatment for primary progressive MS, “we know that about a third of patients will progress despite on being on anti-inflammatory treatment. The same is true for secondary progressive MS. That is the hard core of what we have to think about. We want to improve the efficacy gap between control and active.”
First, Dr. Chataway highlighted the MS-STAT2 trial of simvastatin (Zocor), an inexpensive statin used to lower cholesterol. He is one of the leaders of the 3-year, multicenter, double-blind, randomized, placebo-controlled study, which is testing whether 80-mg daily doses of simvastatin will slow MS progression.
As Dr. Chataway noted, an earlier study – MS-STAT1 – found less brain atrophy in patients who took a high dose of the drug, which was “well tolerated and safe.”
Vascular morbidity drives disability and mortality in MS. “This is low-hanging fruit because we have the tools to do something about it,” he said. “There’s an opportunity here to add into our treatment paradigms across people with MS by actively treating their vascular comorbidity. It will have an effect.”
Recruitment for a trial of this approach is complete, and study results are expected in 2024 and 2025, Dr. Chataway said.
Another new study is exploring the possible effects of the antioxidant lipoic acid, also known as alpha-lipoic acid. As Dr. Chataway noted, a 2017 single-center, randomized, double-blind pilot study of daily oral 1,200 mg lipoic acid versus placebo linked the intervention to a dramatic lowering of brain atrophy – by about 50%.
The new LAPMS study, sponsored by the Veterans Administration, will explore whether lipoic acid affects walking ability, clinical outcome, and brain atrophy, Dr. Chataway said. Results from phase 2 are expected in a year or two, he said.
Dr. Chataway also highlighted one of his own trials, the OCTOPUS study, a multiarm, multistage study that will examine multiple drugs to treat progressive MS. It’s starting with metformin and will look at lipoic acid too, he said.
He also noted the phase 2 CALLIPER trial, which has completed enrollment and expects to provide top-line data in 2025. The multicenter, randomized, double-blind, placebo-controlled will test vidofludimus calcium in patients with progressive MS.
Finally, Dr. Chataway highlighted the randomized, double-blind, placebo-controlled, add-on phase 2 NACPMS trial of n-acetyl cysteine and the phase 1 randomized, double-blind, placebo-controlled trial of SAR443820, a central nervous system penetrant oral RIPK1 inhibitor.
Dr. Chataway discloses grants (UK Multiple Sclerosis Society, National Multiple Sclerosis Society, Efficacy and Mechanism Evaluation Board, Health Technology Assessment, Multiple Sclerosis Trials Collaboration, and Rosetrees Trust), advisory board service (Azadyne, Biogen, Lucid, Janssen, Merck, NervGen, Novartis, and Roche), other support (National Institute of Health Research Support, University College London Hospitals Biomedical Research Centers funding scheme), and serving as an trial investigator (Canadian MS Society, Ionis, Novartis, and Roche).
MILAN – , neurologist Jeremy Chataway, MD, PhD, of University College London and Queen Square Multiple Sclerosis Center told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting.
“They’re all very different, and I think that’s exciting,” he said. “It’s a rich trial environment.”
The problem: At a median of almost 3 years in treatment for primary progressive MS, “we know that about a third of patients will progress despite on being on anti-inflammatory treatment. The same is true for secondary progressive MS. That is the hard core of what we have to think about. We want to improve the efficacy gap between control and active.”
First, Dr. Chataway highlighted the MS-STAT2 trial of simvastatin (Zocor), an inexpensive statin used to lower cholesterol. He is one of the leaders of the 3-year, multicenter, double-blind, randomized, placebo-controlled study, which is testing whether 80-mg daily doses of simvastatin will slow MS progression.
As Dr. Chataway noted, an earlier study – MS-STAT1 – found less brain atrophy in patients who took a high dose of the drug, which was “well tolerated and safe.”
Vascular morbidity drives disability and mortality in MS. “This is low-hanging fruit because we have the tools to do something about it,” he said. “There’s an opportunity here to add into our treatment paradigms across people with MS by actively treating their vascular comorbidity. It will have an effect.”
Recruitment for a trial of this approach is complete, and study results are expected in 2024 and 2025, Dr. Chataway said.
Another new study is exploring the possible effects of the antioxidant lipoic acid, also known as alpha-lipoic acid. As Dr. Chataway noted, a 2017 single-center, randomized, double-blind pilot study of daily oral 1,200 mg lipoic acid versus placebo linked the intervention to a dramatic lowering of brain atrophy – by about 50%.
The new LAPMS study, sponsored by the Veterans Administration, will explore whether lipoic acid affects walking ability, clinical outcome, and brain atrophy, Dr. Chataway said. Results from phase 2 are expected in a year or two, he said.
Dr. Chataway also highlighted one of his own trials, the OCTOPUS study, a multiarm, multistage study that will examine multiple drugs to treat progressive MS. It’s starting with metformin and will look at lipoic acid too, he said.
He also noted the phase 2 CALLIPER trial, which has completed enrollment and expects to provide top-line data in 2025. The multicenter, randomized, double-blind, placebo-controlled will test vidofludimus calcium in patients with progressive MS.
Finally, Dr. Chataway highlighted the randomized, double-blind, placebo-controlled, add-on phase 2 NACPMS trial of n-acetyl cysteine and the phase 1 randomized, double-blind, placebo-controlled trial of SAR443820, a central nervous system penetrant oral RIPK1 inhibitor.
Dr. Chataway discloses grants (UK Multiple Sclerosis Society, National Multiple Sclerosis Society, Efficacy and Mechanism Evaluation Board, Health Technology Assessment, Multiple Sclerosis Trials Collaboration, and Rosetrees Trust), advisory board service (Azadyne, Biogen, Lucid, Janssen, Merck, NervGen, Novartis, and Roche), other support (National Institute of Health Research Support, University College London Hospitals Biomedical Research Centers funding scheme), and serving as an trial investigator (Canadian MS Society, Ionis, Novartis, and Roche).
AT ECTRIMS 2023
AI tool reveals MS drug interactions, offers safer options
MILAN – , German researchers reported.
The team fed the medication plans of almost 630 patients into a deep neural network, which identified drug-drug interactions in more than 80% of cases, in particular when switching from one medication to another, alongside potential food interactions.
The tool was able to identify specific interactions that could be avoided if a drug was replaced with one with a similar pharmacologic profile, but a lower risk of adverse effects.
“Potential drug-drug interactions are a major safety concern in patients with MS,” said study presenter Michael Hecker, PhD, department of neurology, Rostock (Germany) University Medical Center.
Such deep learning–based methods are “useful” in screening for potential interactions both between drugs and with foods, they concluded.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Unknown interactions
During his presentation, Dr. Hecker noted that most patients with MS take two or more drugs “to treat their disease and to mitigate their symptoms and comorbidities.” He pointed out, however, that patients who take multiple medications are at an increased risk for side effects, as one drug may affect the pharmacokinetic or pharmacodynamic properties of another.
“For instance, it may change its metabolism,” Dr. Hecker said, and therefore affect its mechanism of action and the response to the drug, with medications potentially having synergistic, antagonistic, or additive effects.
He explained that the online DrugBank database “provides a huge collection” of known drug-drug interactions for compounds that have a track record. “However, for other drugs, and especially those that are tested only in clinical trials, there’s no information about drug-drug and drug-food interactions,” Dr. Hecker said.
“Moreover, it is quite time-consuming to search a database for individual drug-drug interactions,” he added.
34 million parameters
Consequently, there is increasing interest in the use of deep neural networks to study drug-drug interactions, Dr. Hecker said. DeepDDI is the “state-of-the-art deep learning framework” for predicting interactions. It takes drug-drug or drug-food pairs and compares their structures to determine their similarity. This information is fed into a deep neural network with almost 34 million trainable parameters.
The framework then provides a prediction of any interactions in the same terms as the DrugBank, suggesting, for example, that Drug A may decrease the antihypertensive activities of Drug B.
For the current study, the researchers trained the deep neural network on the most recent release of the DrugBank database, finding it was able to replicate the drug-drug interactions in the database at an accuracy of 92.2% in the validation set and 92.1% in the testing set. They then put the medication plans of 627 patients with MS into the deep neural network.
The patients had a mean age of 48.6 years, 70.3% were women, and the median disease duration was 10 years. They were taking an average of 5.3 medications, and 62% were using disease-modifying therapies (DMT).
The team compared the structures of the drugs they were taking with those of 367 drugs used for the treatment of MS, as well as with structural data for 1,673 food compounds from the FooDB database.
Swapping drugs could reduce interactions
The overall prevalence of potential drug-drug interactions among the patients included in the study was 81.2%.
The researchers then determined the proportion of patients who would be at risk of additional drug-drug interaction if they switched from one DMT to another, or to a Bruton tyrosine kinase inhibitor, given all their other medications.
They found, for example, that more than 40% of patients who switched to the immunomodulator fingolimod (Gilenya) would be at increased risk for bradycardia.
Just under 40% of patients who changed their DMT to the purine analogue cladribine (Mavenclad) would have an increased risk, or worsening, of bleeding, as would approximately 25% of those who switched to the anthracenedione antineoplastic agent mitoxantrone (Novantrone).
Dr. Hecker also showed the deep neural network could make suggestions as to how critical drug-drug interactions could be avoided by replacing interacting drugs with alternatives that have similar pharmacological effects.
For example, carbamazepine (Tegretol, Equetro) could be replaced with topiramate (several brand names) to avoid hepatotoxicity in patients also taking acetaminophen, while liothyronine (Cytomel, Triostat) could replace levothyroxine in patients also taking teriflunomide (Aubagio).
Finally, Dr. Hecker reported there was a subset of 6,860 potential drug-food interactions with the patients’ medications, resulting in reduced or increased concentrations of the drugs, particularly with fish or mushroom consumption.
He conceded, however, there were several limitations to their study, including that it included only small-molecule drugs, and that they did not ask patients about their diet or if they had observed any undesired drug effects.
Furthermore, “only a small number” of the potential drug-drug or drug-food interactions they identified would be “clinically relevant.”
Dr. Hecker also pointed out that each drug has one record, but it is used for different indications, with different dosages, and has different side effects, depending how it is used. “The model does not distinguish this,” he said, and so some of the interactions it highlights could be related to other doses than the one used in MS, for example.
Promise for the future
Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, commented that, as with all AI tools, “it’s only as good as what we’re putting into it.”
Dr. Bhargava, who cochaired the session, said that “there’s limitations on the information in the databases” that are being fed into the deep neural network.
He also highlighted that, “at this point, it didn’t seem like it was coming up with much clinically useful information,” but noted that, “we may get to that point.”
“Right now, there’s promise,” Dr. Bhargava said, but “it’s still not quite there.”
No funding was declared. Dr. Hecker declares relationships with Bayer HealthCare, Biogen, Merck Healthcare, Novartis, and Teva. Several other coauthors also declared financial relationships with industry.
A version of this article first appeared on Medscape.com.
MILAN – , German researchers reported.
The team fed the medication plans of almost 630 patients into a deep neural network, which identified drug-drug interactions in more than 80% of cases, in particular when switching from one medication to another, alongside potential food interactions.
The tool was able to identify specific interactions that could be avoided if a drug was replaced with one with a similar pharmacologic profile, but a lower risk of adverse effects.
“Potential drug-drug interactions are a major safety concern in patients with MS,” said study presenter Michael Hecker, PhD, department of neurology, Rostock (Germany) University Medical Center.
Such deep learning–based methods are “useful” in screening for potential interactions both between drugs and with foods, they concluded.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Unknown interactions
During his presentation, Dr. Hecker noted that most patients with MS take two or more drugs “to treat their disease and to mitigate their symptoms and comorbidities.” He pointed out, however, that patients who take multiple medications are at an increased risk for side effects, as one drug may affect the pharmacokinetic or pharmacodynamic properties of another.
“For instance, it may change its metabolism,” Dr. Hecker said, and therefore affect its mechanism of action and the response to the drug, with medications potentially having synergistic, antagonistic, or additive effects.
He explained that the online DrugBank database “provides a huge collection” of known drug-drug interactions for compounds that have a track record. “However, for other drugs, and especially those that are tested only in clinical trials, there’s no information about drug-drug and drug-food interactions,” Dr. Hecker said.
“Moreover, it is quite time-consuming to search a database for individual drug-drug interactions,” he added.
34 million parameters
Consequently, there is increasing interest in the use of deep neural networks to study drug-drug interactions, Dr. Hecker said. DeepDDI is the “state-of-the-art deep learning framework” for predicting interactions. It takes drug-drug or drug-food pairs and compares their structures to determine their similarity. This information is fed into a deep neural network with almost 34 million trainable parameters.
The framework then provides a prediction of any interactions in the same terms as the DrugBank, suggesting, for example, that Drug A may decrease the antihypertensive activities of Drug B.
For the current study, the researchers trained the deep neural network on the most recent release of the DrugBank database, finding it was able to replicate the drug-drug interactions in the database at an accuracy of 92.2% in the validation set and 92.1% in the testing set. They then put the medication plans of 627 patients with MS into the deep neural network.
The patients had a mean age of 48.6 years, 70.3% were women, and the median disease duration was 10 years. They were taking an average of 5.3 medications, and 62% were using disease-modifying therapies (DMT).
The team compared the structures of the drugs they were taking with those of 367 drugs used for the treatment of MS, as well as with structural data for 1,673 food compounds from the FooDB database.
Swapping drugs could reduce interactions
The overall prevalence of potential drug-drug interactions among the patients included in the study was 81.2%.
The researchers then determined the proportion of patients who would be at risk of additional drug-drug interaction if they switched from one DMT to another, or to a Bruton tyrosine kinase inhibitor, given all their other medications.
They found, for example, that more than 40% of patients who switched to the immunomodulator fingolimod (Gilenya) would be at increased risk for bradycardia.
Just under 40% of patients who changed their DMT to the purine analogue cladribine (Mavenclad) would have an increased risk, or worsening, of bleeding, as would approximately 25% of those who switched to the anthracenedione antineoplastic agent mitoxantrone (Novantrone).
Dr. Hecker also showed the deep neural network could make suggestions as to how critical drug-drug interactions could be avoided by replacing interacting drugs with alternatives that have similar pharmacological effects.
For example, carbamazepine (Tegretol, Equetro) could be replaced with topiramate (several brand names) to avoid hepatotoxicity in patients also taking acetaminophen, while liothyronine (Cytomel, Triostat) could replace levothyroxine in patients also taking teriflunomide (Aubagio).
Finally, Dr. Hecker reported there was a subset of 6,860 potential drug-food interactions with the patients’ medications, resulting in reduced or increased concentrations of the drugs, particularly with fish or mushroom consumption.
He conceded, however, there were several limitations to their study, including that it included only small-molecule drugs, and that they did not ask patients about their diet or if they had observed any undesired drug effects.
Furthermore, “only a small number” of the potential drug-drug or drug-food interactions they identified would be “clinically relevant.”
Dr. Hecker also pointed out that each drug has one record, but it is used for different indications, with different dosages, and has different side effects, depending how it is used. “The model does not distinguish this,” he said, and so some of the interactions it highlights could be related to other doses than the one used in MS, for example.
Promise for the future
Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, commented that, as with all AI tools, “it’s only as good as what we’re putting into it.”
Dr. Bhargava, who cochaired the session, said that “there’s limitations on the information in the databases” that are being fed into the deep neural network.
He also highlighted that, “at this point, it didn’t seem like it was coming up with much clinically useful information,” but noted that, “we may get to that point.”
“Right now, there’s promise,” Dr. Bhargava said, but “it’s still not quite there.”
No funding was declared. Dr. Hecker declares relationships with Bayer HealthCare, Biogen, Merck Healthcare, Novartis, and Teva. Several other coauthors also declared financial relationships with industry.
A version of this article first appeared on Medscape.com.
MILAN – , German researchers reported.
The team fed the medication plans of almost 630 patients into a deep neural network, which identified drug-drug interactions in more than 80% of cases, in particular when switching from one medication to another, alongside potential food interactions.
The tool was able to identify specific interactions that could be avoided if a drug was replaced with one with a similar pharmacologic profile, but a lower risk of adverse effects.
“Potential drug-drug interactions are a major safety concern in patients with MS,” said study presenter Michael Hecker, PhD, department of neurology, Rostock (Germany) University Medical Center.
Such deep learning–based methods are “useful” in screening for potential interactions both between drugs and with foods, they concluded.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Unknown interactions
During his presentation, Dr. Hecker noted that most patients with MS take two or more drugs “to treat their disease and to mitigate their symptoms and comorbidities.” He pointed out, however, that patients who take multiple medications are at an increased risk for side effects, as one drug may affect the pharmacokinetic or pharmacodynamic properties of another.
“For instance, it may change its metabolism,” Dr. Hecker said, and therefore affect its mechanism of action and the response to the drug, with medications potentially having synergistic, antagonistic, or additive effects.
He explained that the online DrugBank database “provides a huge collection” of known drug-drug interactions for compounds that have a track record. “However, for other drugs, and especially those that are tested only in clinical trials, there’s no information about drug-drug and drug-food interactions,” Dr. Hecker said.
“Moreover, it is quite time-consuming to search a database for individual drug-drug interactions,” he added.
34 million parameters
Consequently, there is increasing interest in the use of deep neural networks to study drug-drug interactions, Dr. Hecker said. DeepDDI is the “state-of-the-art deep learning framework” for predicting interactions. It takes drug-drug or drug-food pairs and compares their structures to determine their similarity. This information is fed into a deep neural network with almost 34 million trainable parameters.
The framework then provides a prediction of any interactions in the same terms as the DrugBank, suggesting, for example, that Drug A may decrease the antihypertensive activities of Drug B.
For the current study, the researchers trained the deep neural network on the most recent release of the DrugBank database, finding it was able to replicate the drug-drug interactions in the database at an accuracy of 92.2% in the validation set and 92.1% in the testing set. They then put the medication plans of 627 patients with MS into the deep neural network.
The patients had a mean age of 48.6 years, 70.3% were women, and the median disease duration was 10 years. They were taking an average of 5.3 medications, and 62% were using disease-modifying therapies (DMT).
The team compared the structures of the drugs they were taking with those of 367 drugs used for the treatment of MS, as well as with structural data for 1,673 food compounds from the FooDB database.
Swapping drugs could reduce interactions
The overall prevalence of potential drug-drug interactions among the patients included in the study was 81.2%.
The researchers then determined the proportion of patients who would be at risk of additional drug-drug interaction if they switched from one DMT to another, or to a Bruton tyrosine kinase inhibitor, given all their other medications.
They found, for example, that more than 40% of patients who switched to the immunomodulator fingolimod (Gilenya) would be at increased risk for bradycardia.
Just under 40% of patients who changed their DMT to the purine analogue cladribine (Mavenclad) would have an increased risk, or worsening, of bleeding, as would approximately 25% of those who switched to the anthracenedione antineoplastic agent mitoxantrone (Novantrone).
Dr. Hecker also showed the deep neural network could make suggestions as to how critical drug-drug interactions could be avoided by replacing interacting drugs with alternatives that have similar pharmacological effects.
For example, carbamazepine (Tegretol, Equetro) could be replaced with topiramate (several brand names) to avoid hepatotoxicity in patients also taking acetaminophen, while liothyronine (Cytomel, Triostat) could replace levothyroxine in patients also taking teriflunomide (Aubagio).
Finally, Dr. Hecker reported there was a subset of 6,860 potential drug-food interactions with the patients’ medications, resulting in reduced or increased concentrations of the drugs, particularly with fish or mushroom consumption.
He conceded, however, there were several limitations to their study, including that it included only small-molecule drugs, and that they did not ask patients about their diet or if they had observed any undesired drug effects.
Furthermore, “only a small number” of the potential drug-drug or drug-food interactions they identified would be “clinically relevant.”
Dr. Hecker also pointed out that each drug has one record, but it is used for different indications, with different dosages, and has different side effects, depending how it is used. “The model does not distinguish this,” he said, and so some of the interactions it highlights could be related to other doses than the one used in MS, for example.
Promise for the future
Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, commented that, as with all AI tools, “it’s only as good as what we’re putting into it.”
Dr. Bhargava, who cochaired the session, said that “there’s limitations on the information in the databases” that are being fed into the deep neural network.
He also highlighted that, “at this point, it didn’t seem like it was coming up with much clinically useful information,” but noted that, “we may get to that point.”
“Right now, there’s promise,” Dr. Bhargava said, but “it’s still not quite there.”
No funding was declared. Dr. Hecker declares relationships with Bayer HealthCare, Biogen, Merck Healthcare, Novartis, and Teva. Several other coauthors also declared financial relationships with industry.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2023