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Multiple changes in NMOSD treatment for nonmedical reasons tied to poorer outcomes
DENVER – , new research shows.
“For the first time, we were able to quantify clinical outcomes associated with treatment transitions in people with NMOSD. Our data highlight that aspects outside of therapeutic efficacy may be remarkably meaningful in the effective suppression of disease advancement,” said senior investigator Darin T. Okuda, MD, professor of neurology and director of the neuroinnovation program at University of Texas Southwestern Medical Center in Dallas.
The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Treatment delayed?
NMOSD, an inflammatory syndrome of the central nervous system, can cause irreversible disability. As treatments have improved over time, transitioning from one medication to newer options has become increasingly common.
To better understand the effects of multiple treatment transitions, the researchers conducted a retrospective analysis of electronic medical records of 164 patients with aquaporin-4 IgG–positive NMOSD. Of these individuals, 89 met the study’s inclusion criteria.
Of the participants, 89% were female, and the median disease duration was 10.1 years. Forty-two patients had switched therapies at least once; 26 switched at least twice; 12 switched at least three times; six switched four times; and three switched therapies five times or more for a total of 174 treatment transitions.
Patients were stratified into two groups – those who transitioned for medical reasons (53.4%), and those who switched because of nonmedical/tolerability reasons (46.6%).
Top reasons for transitioning in the medical category included clinical relapse and/or new MRI activity (29.9%), physician-directed transition (11.5%), and increased physical or clinical disability (4.0%). Leading reasons for nonmedical transitions were side effects (16.7%), adherence/persistence (8.1%), and cost/access (5.75%).
A recurrent event survival analysis showed that, after just one transition for nonmedical or tolerability reasons, outcomes significantly improved, with the risk of hospitalization decreasing 40.3% (P = .005), the risk of relapse decreasing by 53.1% (P = .002), and the risk of advancement on MRI decreasing by 65.9% (P = .005).
Conversely, each additional drug discontinuation in the nonmedical group was associated with worse outcomes. These included a 25.2% increased risk of hospitalization (P = .0003), a 24.4% increase in relapse risk (P = .06), and a 41.9% increased risk of MRI advancement (P = .03).
In terms of transitions for medical reasons, there was a significantly increased risk of MRI advancement with the first switch (32.2%; P = .005). However, no significant increases in risk were associated with each additional transition (P = .33).
The median time spent on the first treatment was 306 days in the transition for medical reasons group and 378 days for the nonmedical/tolerability group.
The median duration of time spent between treatments during the initial transition was just 7 days among those transitioning for medical reasons versus 91 days for nonmedical reasons, with the median duration of additional transitions also substantially longer in the nonmedical reasons group, at 22 and 80 days, respectively.
“The median time spent on a first-line therapy regardless of [whether] that first transition was due to a medical or nonmedical tolerability reason was similar; however, the duration of that initial transition was 13 times longer if the transition had to do with a nonmedical or tolerability reason,” first author Alexander D. Smith, a clinical data specialist at UT Southwestern Medical Center, told conference delegates. “Similarly, each additional transition was almost four times longer if it had to do with a nonmedical or tolerability reason,” he said.
Dr. Okuda noted the longer window between treatment transitions may be a key factor in the different outcomes between the groups. “A central theory involves the increased amount of time between treatments,” he said.
“The reasons for the delay in starting a new treatment may be related to a variety of factors, including laboratory testing required to start a new treatment, third-party administrator coverage, time for the resolution of adverse reactions, and/or personal factors from the individual undergoing treatment, etc.”
Another factor, Mr. Smith said in his talk, is that, “when people are left miserable by a prior treatment exposure, they may simply be hesitant to get on the next therapy.”
The finding that only MRI advancement was associated with transitions for medical reasons suggests that worsening disease activity is not necessarily behind increased transitions, with nonmedical reasons often the cause, and more likely to be associated with the worse outcomes.
With the time between treatments a possible culprit, Dr. Okuda said the clinical implications are that “treatment transitions, regardless of the reason, should occur as quickly as possible to reduce the risk for disease progression associated with NMOSD.”
Mr. Smith echoed the suggestion, adding that “it’s important that even if disease activity is not present, complacency should be avoided.”
“Clinicians and third-party administrators should work to ensure that people with NMOSD have accelerated switches onto their next therapy, even if that disease activity is not present. In a sense, rapid treatment transitions may have equitable benefits to the treatments themselves,” Mr. Smith added.
Important research
Commenting on the study, Shailee Shah, MD, an assistant professor in the Neuroimmunology division at Vanderbilt University Medical Center, in Nashville, Tenn., noted the findings are consistent with generally higher concerns around switching treatments for nonmedical reasons.
“In general, if a high-efficacy medication is started, it appears that patients are less likely to require a transition to a different medication. It is a little harder to predict who may have issues with tolerability or nonmedical reasons to transition medications, and many providers would likely agree that these transitions do raise some concerns about the risk of relapse or hospitalization in the interim,” she said.
Dr. Shah added that in her experience patients who require multiple transitions are either started on lower-efficacy medications at treatment initiation or have highly refractory disease.
The study’s findings underscore that “identifying additional risk factors and underlying reasons for these findings will be imperative in the future,” Dr. Shah said.
The study was supported by Revert Health, a corporation founded by Dr. Okuda. Dr. Okuda reports receiving personal compensation for consulting and advisory services from Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Janssen Pharmaceuticals, Novartis, Osmotica Pharmaceuticals, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, and research support from Biogen, EMD Serono/Merck, and Novartis. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.
A version of this article first appeared on Medscape.com.
DENVER – , new research shows.
“For the first time, we were able to quantify clinical outcomes associated with treatment transitions in people with NMOSD. Our data highlight that aspects outside of therapeutic efficacy may be remarkably meaningful in the effective suppression of disease advancement,” said senior investigator Darin T. Okuda, MD, professor of neurology and director of the neuroinnovation program at University of Texas Southwestern Medical Center in Dallas.
The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Treatment delayed?
NMOSD, an inflammatory syndrome of the central nervous system, can cause irreversible disability. As treatments have improved over time, transitioning from one medication to newer options has become increasingly common.
To better understand the effects of multiple treatment transitions, the researchers conducted a retrospective analysis of electronic medical records of 164 patients with aquaporin-4 IgG–positive NMOSD. Of these individuals, 89 met the study’s inclusion criteria.
Of the participants, 89% were female, and the median disease duration was 10.1 years. Forty-two patients had switched therapies at least once; 26 switched at least twice; 12 switched at least three times; six switched four times; and three switched therapies five times or more for a total of 174 treatment transitions.
Patients were stratified into two groups – those who transitioned for medical reasons (53.4%), and those who switched because of nonmedical/tolerability reasons (46.6%).
Top reasons for transitioning in the medical category included clinical relapse and/or new MRI activity (29.9%), physician-directed transition (11.5%), and increased physical or clinical disability (4.0%). Leading reasons for nonmedical transitions were side effects (16.7%), adherence/persistence (8.1%), and cost/access (5.75%).
A recurrent event survival analysis showed that, after just one transition for nonmedical or tolerability reasons, outcomes significantly improved, with the risk of hospitalization decreasing 40.3% (P = .005), the risk of relapse decreasing by 53.1% (P = .002), and the risk of advancement on MRI decreasing by 65.9% (P = .005).
Conversely, each additional drug discontinuation in the nonmedical group was associated with worse outcomes. These included a 25.2% increased risk of hospitalization (P = .0003), a 24.4% increase in relapse risk (P = .06), and a 41.9% increased risk of MRI advancement (P = .03).
In terms of transitions for medical reasons, there was a significantly increased risk of MRI advancement with the first switch (32.2%; P = .005). However, no significant increases in risk were associated with each additional transition (P = .33).
The median time spent on the first treatment was 306 days in the transition for medical reasons group and 378 days for the nonmedical/tolerability group.
The median duration of time spent between treatments during the initial transition was just 7 days among those transitioning for medical reasons versus 91 days for nonmedical reasons, with the median duration of additional transitions also substantially longer in the nonmedical reasons group, at 22 and 80 days, respectively.
“The median time spent on a first-line therapy regardless of [whether] that first transition was due to a medical or nonmedical tolerability reason was similar; however, the duration of that initial transition was 13 times longer if the transition had to do with a nonmedical or tolerability reason,” first author Alexander D. Smith, a clinical data specialist at UT Southwestern Medical Center, told conference delegates. “Similarly, each additional transition was almost four times longer if it had to do with a nonmedical or tolerability reason,” he said.
Dr. Okuda noted the longer window between treatment transitions may be a key factor in the different outcomes between the groups. “A central theory involves the increased amount of time between treatments,” he said.
“The reasons for the delay in starting a new treatment may be related to a variety of factors, including laboratory testing required to start a new treatment, third-party administrator coverage, time for the resolution of adverse reactions, and/or personal factors from the individual undergoing treatment, etc.”
Another factor, Mr. Smith said in his talk, is that, “when people are left miserable by a prior treatment exposure, they may simply be hesitant to get on the next therapy.”
The finding that only MRI advancement was associated with transitions for medical reasons suggests that worsening disease activity is not necessarily behind increased transitions, with nonmedical reasons often the cause, and more likely to be associated with the worse outcomes.
With the time between treatments a possible culprit, Dr. Okuda said the clinical implications are that “treatment transitions, regardless of the reason, should occur as quickly as possible to reduce the risk for disease progression associated with NMOSD.”
Mr. Smith echoed the suggestion, adding that “it’s important that even if disease activity is not present, complacency should be avoided.”
“Clinicians and third-party administrators should work to ensure that people with NMOSD have accelerated switches onto their next therapy, even if that disease activity is not present. In a sense, rapid treatment transitions may have equitable benefits to the treatments themselves,” Mr. Smith added.
Important research
Commenting on the study, Shailee Shah, MD, an assistant professor in the Neuroimmunology division at Vanderbilt University Medical Center, in Nashville, Tenn., noted the findings are consistent with generally higher concerns around switching treatments for nonmedical reasons.
“In general, if a high-efficacy medication is started, it appears that patients are less likely to require a transition to a different medication. It is a little harder to predict who may have issues with tolerability or nonmedical reasons to transition medications, and many providers would likely agree that these transitions do raise some concerns about the risk of relapse or hospitalization in the interim,” she said.
Dr. Shah added that in her experience patients who require multiple transitions are either started on lower-efficacy medications at treatment initiation or have highly refractory disease.
The study’s findings underscore that “identifying additional risk factors and underlying reasons for these findings will be imperative in the future,” Dr. Shah said.
The study was supported by Revert Health, a corporation founded by Dr. Okuda. Dr. Okuda reports receiving personal compensation for consulting and advisory services from Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Janssen Pharmaceuticals, Novartis, Osmotica Pharmaceuticals, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, and research support from Biogen, EMD Serono/Merck, and Novartis. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.
A version of this article first appeared on Medscape.com.
DENVER – , new research shows.
“For the first time, we were able to quantify clinical outcomes associated with treatment transitions in people with NMOSD. Our data highlight that aspects outside of therapeutic efficacy may be remarkably meaningful in the effective suppression of disease advancement,” said senior investigator Darin T. Okuda, MD, professor of neurology and director of the neuroinnovation program at University of Texas Southwestern Medical Center in Dallas.
The findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Treatment delayed?
NMOSD, an inflammatory syndrome of the central nervous system, can cause irreversible disability. As treatments have improved over time, transitioning from one medication to newer options has become increasingly common.
To better understand the effects of multiple treatment transitions, the researchers conducted a retrospective analysis of electronic medical records of 164 patients with aquaporin-4 IgG–positive NMOSD. Of these individuals, 89 met the study’s inclusion criteria.
Of the participants, 89% were female, and the median disease duration was 10.1 years. Forty-two patients had switched therapies at least once; 26 switched at least twice; 12 switched at least three times; six switched four times; and three switched therapies five times or more for a total of 174 treatment transitions.
Patients were stratified into two groups – those who transitioned for medical reasons (53.4%), and those who switched because of nonmedical/tolerability reasons (46.6%).
Top reasons for transitioning in the medical category included clinical relapse and/or new MRI activity (29.9%), physician-directed transition (11.5%), and increased physical or clinical disability (4.0%). Leading reasons for nonmedical transitions were side effects (16.7%), adherence/persistence (8.1%), and cost/access (5.75%).
A recurrent event survival analysis showed that, after just one transition for nonmedical or tolerability reasons, outcomes significantly improved, with the risk of hospitalization decreasing 40.3% (P = .005), the risk of relapse decreasing by 53.1% (P = .002), and the risk of advancement on MRI decreasing by 65.9% (P = .005).
Conversely, each additional drug discontinuation in the nonmedical group was associated with worse outcomes. These included a 25.2% increased risk of hospitalization (P = .0003), a 24.4% increase in relapse risk (P = .06), and a 41.9% increased risk of MRI advancement (P = .03).
In terms of transitions for medical reasons, there was a significantly increased risk of MRI advancement with the first switch (32.2%; P = .005). However, no significant increases in risk were associated with each additional transition (P = .33).
The median time spent on the first treatment was 306 days in the transition for medical reasons group and 378 days for the nonmedical/tolerability group.
The median duration of time spent between treatments during the initial transition was just 7 days among those transitioning for medical reasons versus 91 days for nonmedical reasons, with the median duration of additional transitions also substantially longer in the nonmedical reasons group, at 22 and 80 days, respectively.
“The median time spent on a first-line therapy regardless of [whether] that first transition was due to a medical or nonmedical tolerability reason was similar; however, the duration of that initial transition was 13 times longer if the transition had to do with a nonmedical or tolerability reason,” first author Alexander D. Smith, a clinical data specialist at UT Southwestern Medical Center, told conference delegates. “Similarly, each additional transition was almost four times longer if it had to do with a nonmedical or tolerability reason,” he said.
Dr. Okuda noted the longer window between treatment transitions may be a key factor in the different outcomes between the groups. “A central theory involves the increased amount of time between treatments,” he said.
“The reasons for the delay in starting a new treatment may be related to a variety of factors, including laboratory testing required to start a new treatment, third-party administrator coverage, time for the resolution of adverse reactions, and/or personal factors from the individual undergoing treatment, etc.”
Another factor, Mr. Smith said in his talk, is that, “when people are left miserable by a prior treatment exposure, they may simply be hesitant to get on the next therapy.”
The finding that only MRI advancement was associated with transitions for medical reasons suggests that worsening disease activity is not necessarily behind increased transitions, with nonmedical reasons often the cause, and more likely to be associated with the worse outcomes.
With the time between treatments a possible culprit, Dr. Okuda said the clinical implications are that “treatment transitions, regardless of the reason, should occur as quickly as possible to reduce the risk for disease progression associated with NMOSD.”
Mr. Smith echoed the suggestion, adding that “it’s important that even if disease activity is not present, complacency should be avoided.”
“Clinicians and third-party administrators should work to ensure that people with NMOSD have accelerated switches onto their next therapy, even if that disease activity is not present. In a sense, rapid treatment transitions may have equitable benefits to the treatments themselves,” Mr. Smith added.
Important research
Commenting on the study, Shailee Shah, MD, an assistant professor in the Neuroimmunology division at Vanderbilt University Medical Center, in Nashville, Tenn., noted the findings are consistent with generally higher concerns around switching treatments for nonmedical reasons.
“In general, if a high-efficacy medication is started, it appears that patients are less likely to require a transition to a different medication. It is a little harder to predict who may have issues with tolerability or nonmedical reasons to transition medications, and many providers would likely agree that these transitions do raise some concerns about the risk of relapse or hospitalization in the interim,” she said.
Dr. Shah added that in her experience patients who require multiple transitions are either started on lower-efficacy medications at treatment initiation or have highly refractory disease.
The study’s findings underscore that “identifying additional risk factors and underlying reasons for these findings will be imperative in the future,” Dr. Shah said.
The study was supported by Revert Health, a corporation founded by Dr. Okuda. Dr. Okuda reports receiving personal compensation for consulting and advisory services from Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Janssen Pharmaceuticals, Novartis, Osmotica Pharmaceuticals, RVL Pharmaceuticals, TG Therapeutics, Viela Bio, and research support from Biogen, EMD Serono/Merck, and Novartis. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.
A version of this article first appeared on Medscape.com.
At CMSC 2023
Racial, ethnic disparities persist in access to MS care
Aurora, Colo. – , according to research on patient-reported health inequities presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
”Equal access to and quality of care are critical for managing a progressive disease such as multiple sclerosis,” said Chris Hardy, of Publicis Health Media, and her associates. “Despite increased awareness of health outcome disparities in the U.S., certain patients still experience inequities in care.”
The researchers sent emails to members of MyMSTeam, an online support network of more than 197,000 members, to request completion of a 34-question online survey. Questions addressed respondents’ ability to access care, resources in their neighborhood, and their interactions with their health care providers. Questions also addressed the burden of MS on individuals’ quality of life, which was considerable across all demographics. The 1,935 patients with MS who responded were overwhelmingly White, though the demographics varied by question.
A ‘widespread and significant problem’
“This study is important in pointing out the unfortunate, obvious [fact] that lack of access and lack of availability to treatment is still a widespread and significant problem in this country,” commented Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates who was not involved in the study. “Improving effective treatment of disease requires a more granular understanding of disease impact on a quantitative, multidimensional, objective patient-centric approach,” he added. “Racial and ethnic barriers to effective treatment cannot be allowed nor tolerated. We need to be more acutely aware that outreach, digital health, and remote assessments are tools that we need to incorporate to improve access and do better.”
The pervasive impact of MS
Overall, 85% of respondents reported that MS made it harder to do everyday chores, and 84% said their MS made it harder to exercise and interfered with their everyday life. Similarly high proportions of respondents reported that their MS causes them a lot of stress (80%), makes them feel anxious or depressed (77%), disrupts their work/employment (75%), and interferes with their social life (75%). In addition, more than half said their diagnosis negatively affects their family (59%) and makes them feel judged (53%).
Deanne Power, RN, MSCN, the lead nurse care partner at Octave Bioscience, who spoke as a representative of the study authors, said it’s critical that clinicians be aware of the health inequities that exist among their patient population.
“Some patients have lower income or language issues where English is not their primary language, and they don’t have access and are even afraid to call doctor or reach out [for help],” Ms. Power said. “If providers aren’t actively aware of these situations and talk to their patients, they can’t just say, ‘Oh, well, I just want you to go fill this prescription,’ when they don’t have money to put food on their table. Providers have got to know their patients as [more than] just an MS patient. This is a human being in front of you, and you better know what their life is like, because it’s impacting their MS.”
Access to care varied by race
Among the 1,906 respondents who answered questions about access to care, 9% were Black, 5% were Hispanic, and the rest were White. In these questions, differences between demographics arose when it came to individuals’ ability to conveniently see an MS specialist and their subsequent use of emergency services. For example, only 64% of Hispanic respondents reported convenient access to a health care provider specializing in MS, compared with 76% of White and 78% of Black respondents.
A significantly higher proportion of Hispanics also reported that they could not take time off from work when they were sick (25%) or to attend a doctor appointment (20%), compared with White (15% and 9%, respectively) and Black (18% and 12%) respondents. Meanwhile, a significantly higher proportion of Hispanics (35%) reported visiting the emergency department in the past year for MS-related issues, compared with White (19%) or Black (25%) respondents.
White respondents consistently had greater convenient access to dental offices, healthy foods, outpatient care, gyms, and parks and trails, compared with Black and Hispanic patients’ access. For example, 85% of White patients had convenient access to dental offices and 72% had access to outpatient care, compared with Black (74% and 65%) and Hispanic (78% and 52%) patients. Two-thirds of Hispanic respondents (67%) reported access to healthy foods and to gyms, parks, or trails, compared with more than three-quarters of both White and Black patients.
Other barriers to MS care
Both racial/ethnic and gender disparities emerged in how patients felt treated by their health care providers. Men were significantly more likely (70%) than women (65%) to say their health care provider listens to and understands them. A statistically significant higher proportion of men (71%) also said their clinician explained their MS test results to them, compared with women (62%), and only 28% of women, versus 37% of men, said their provider developed a long-term plan for them.
Anne Foelsch, the vice president of strategic partnerships at MyHealthTeam, who works with the authors, noted the large discrepancy that was seen particularly for Hispanic patients in terms of how they felt treated by their health care provider.
“Doctors might perceive that the relationship is the same with all of their patients when their patients have a very different perception of what that relationship is and whether they’re not being heard,” Ms. Foelsch said. “It’s important that clinicians take a little bit of time and learn a little bit more about a patient’s perspective and what it’s like when they have a chronic condition like MS and how it impacts their life, looking for those nuances that are different based on your ethnicity.”
Just over half of Hispanic patients (54%) said their provider explained their MS test results, compared with nearly two-thirds of White patients (65%) and 61% of Black patients. Hispanic patients were also less likely (55%) to say they felt their provider listens to and understands them than White (67%) or Black (65%) patients. Two-thirds of White respondents (67%) said their doctor recommended regular check-ups, compared with just over half of Black and Hispanic respondents (55%).
Other statistically significant disparities by race/ethnicity, where a higher proportion of White patients responded affirmatively than Black or Hispanic patients, included feeling treated with respect by their health care provider, feeling their provider is nonjudgmental, and saying their provider spends enough time with them, addresses their MS symptoms, and encourages shared decision-making.
“This study nicely documents and points out that despite our best intentions, we need to do much better as a community to help those with chronic and potentially disabling diseases like MS,” Dr. Gudesblatt said. “The racial, ethnic, and gender disparities only result in greater disability and societal costs by those who can least afford it. All therapies fail due to nonadherence, limited access, lack of insurance coverage, limited insurance coverage, high copays, long waits, cultural biases, and more.”
The researchers acknowledged that their survey respondents may not be representative of all patients with MS because the survey relied on those who chose to respond to the online survey.
The study authors were all employees of Publicis Health Media or MyHealthTeam. Dr. Gudesblatt reported no disclosures.
Aurora, Colo. – , according to research on patient-reported health inequities presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
”Equal access to and quality of care are critical for managing a progressive disease such as multiple sclerosis,” said Chris Hardy, of Publicis Health Media, and her associates. “Despite increased awareness of health outcome disparities in the U.S., certain patients still experience inequities in care.”
The researchers sent emails to members of MyMSTeam, an online support network of more than 197,000 members, to request completion of a 34-question online survey. Questions addressed respondents’ ability to access care, resources in their neighborhood, and their interactions with their health care providers. Questions also addressed the burden of MS on individuals’ quality of life, which was considerable across all demographics. The 1,935 patients with MS who responded were overwhelmingly White, though the demographics varied by question.
A ‘widespread and significant problem’
“This study is important in pointing out the unfortunate, obvious [fact] that lack of access and lack of availability to treatment is still a widespread and significant problem in this country,” commented Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates who was not involved in the study. “Improving effective treatment of disease requires a more granular understanding of disease impact on a quantitative, multidimensional, objective patient-centric approach,” he added. “Racial and ethnic barriers to effective treatment cannot be allowed nor tolerated. We need to be more acutely aware that outreach, digital health, and remote assessments are tools that we need to incorporate to improve access and do better.”
The pervasive impact of MS
Overall, 85% of respondents reported that MS made it harder to do everyday chores, and 84% said their MS made it harder to exercise and interfered with their everyday life. Similarly high proportions of respondents reported that their MS causes them a lot of stress (80%), makes them feel anxious or depressed (77%), disrupts their work/employment (75%), and interferes with their social life (75%). In addition, more than half said their diagnosis negatively affects their family (59%) and makes them feel judged (53%).
Deanne Power, RN, MSCN, the lead nurse care partner at Octave Bioscience, who spoke as a representative of the study authors, said it’s critical that clinicians be aware of the health inequities that exist among their patient population.
“Some patients have lower income or language issues where English is not their primary language, and they don’t have access and are even afraid to call doctor or reach out [for help],” Ms. Power said. “If providers aren’t actively aware of these situations and talk to their patients, they can’t just say, ‘Oh, well, I just want you to go fill this prescription,’ when they don’t have money to put food on their table. Providers have got to know their patients as [more than] just an MS patient. This is a human being in front of you, and you better know what their life is like, because it’s impacting their MS.”
Access to care varied by race
Among the 1,906 respondents who answered questions about access to care, 9% were Black, 5% were Hispanic, and the rest were White. In these questions, differences between demographics arose when it came to individuals’ ability to conveniently see an MS specialist and their subsequent use of emergency services. For example, only 64% of Hispanic respondents reported convenient access to a health care provider specializing in MS, compared with 76% of White and 78% of Black respondents.
A significantly higher proportion of Hispanics also reported that they could not take time off from work when they were sick (25%) or to attend a doctor appointment (20%), compared with White (15% and 9%, respectively) and Black (18% and 12%) respondents. Meanwhile, a significantly higher proportion of Hispanics (35%) reported visiting the emergency department in the past year for MS-related issues, compared with White (19%) or Black (25%) respondents.
White respondents consistently had greater convenient access to dental offices, healthy foods, outpatient care, gyms, and parks and trails, compared with Black and Hispanic patients’ access. For example, 85% of White patients had convenient access to dental offices and 72% had access to outpatient care, compared with Black (74% and 65%) and Hispanic (78% and 52%) patients. Two-thirds of Hispanic respondents (67%) reported access to healthy foods and to gyms, parks, or trails, compared with more than three-quarters of both White and Black patients.
Other barriers to MS care
Both racial/ethnic and gender disparities emerged in how patients felt treated by their health care providers. Men were significantly more likely (70%) than women (65%) to say their health care provider listens to and understands them. A statistically significant higher proportion of men (71%) also said their clinician explained their MS test results to them, compared with women (62%), and only 28% of women, versus 37% of men, said their provider developed a long-term plan for them.
Anne Foelsch, the vice president of strategic partnerships at MyHealthTeam, who works with the authors, noted the large discrepancy that was seen particularly for Hispanic patients in terms of how they felt treated by their health care provider.
“Doctors might perceive that the relationship is the same with all of their patients when their patients have a very different perception of what that relationship is and whether they’re not being heard,” Ms. Foelsch said. “It’s important that clinicians take a little bit of time and learn a little bit more about a patient’s perspective and what it’s like when they have a chronic condition like MS and how it impacts their life, looking for those nuances that are different based on your ethnicity.”
Just over half of Hispanic patients (54%) said their provider explained their MS test results, compared with nearly two-thirds of White patients (65%) and 61% of Black patients. Hispanic patients were also less likely (55%) to say they felt their provider listens to and understands them than White (67%) or Black (65%) patients. Two-thirds of White respondents (67%) said their doctor recommended regular check-ups, compared with just over half of Black and Hispanic respondents (55%).
Other statistically significant disparities by race/ethnicity, where a higher proportion of White patients responded affirmatively than Black or Hispanic patients, included feeling treated with respect by their health care provider, feeling their provider is nonjudgmental, and saying their provider spends enough time with them, addresses their MS symptoms, and encourages shared decision-making.
“This study nicely documents and points out that despite our best intentions, we need to do much better as a community to help those with chronic and potentially disabling diseases like MS,” Dr. Gudesblatt said. “The racial, ethnic, and gender disparities only result in greater disability and societal costs by those who can least afford it. All therapies fail due to nonadherence, limited access, lack of insurance coverage, limited insurance coverage, high copays, long waits, cultural biases, and more.”
The researchers acknowledged that their survey respondents may not be representative of all patients with MS because the survey relied on those who chose to respond to the online survey.
The study authors were all employees of Publicis Health Media or MyHealthTeam. Dr. Gudesblatt reported no disclosures.
Aurora, Colo. – , according to research on patient-reported health inequities presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
”Equal access to and quality of care are critical for managing a progressive disease such as multiple sclerosis,” said Chris Hardy, of Publicis Health Media, and her associates. “Despite increased awareness of health outcome disparities in the U.S., certain patients still experience inequities in care.”
The researchers sent emails to members of MyMSTeam, an online support network of more than 197,000 members, to request completion of a 34-question online survey. Questions addressed respondents’ ability to access care, resources in their neighborhood, and their interactions with their health care providers. Questions also addressed the burden of MS on individuals’ quality of life, which was considerable across all demographics. The 1,935 patients with MS who responded were overwhelmingly White, though the demographics varied by question.
A ‘widespread and significant problem’
“This study is important in pointing out the unfortunate, obvious [fact] that lack of access and lack of availability to treatment is still a widespread and significant problem in this country,” commented Mark Gudesblatt, MD, a neurologist at South Shore Neurologic Associates who was not involved in the study. “Improving effective treatment of disease requires a more granular understanding of disease impact on a quantitative, multidimensional, objective patient-centric approach,” he added. “Racial and ethnic barriers to effective treatment cannot be allowed nor tolerated. We need to be more acutely aware that outreach, digital health, and remote assessments are tools that we need to incorporate to improve access and do better.”
The pervasive impact of MS
Overall, 85% of respondents reported that MS made it harder to do everyday chores, and 84% said their MS made it harder to exercise and interfered with their everyday life. Similarly high proportions of respondents reported that their MS causes them a lot of stress (80%), makes them feel anxious or depressed (77%), disrupts their work/employment (75%), and interferes with their social life (75%). In addition, more than half said their diagnosis negatively affects their family (59%) and makes them feel judged (53%).
Deanne Power, RN, MSCN, the lead nurse care partner at Octave Bioscience, who spoke as a representative of the study authors, said it’s critical that clinicians be aware of the health inequities that exist among their patient population.
“Some patients have lower income or language issues where English is not their primary language, and they don’t have access and are even afraid to call doctor or reach out [for help],” Ms. Power said. “If providers aren’t actively aware of these situations and talk to their patients, they can’t just say, ‘Oh, well, I just want you to go fill this prescription,’ when they don’t have money to put food on their table. Providers have got to know their patients as [more than] just an MS patient. This is a human being in front of you, and you better know what their life is like, because it’s impacting their MS.”
Access to care varied by race
Among the 1,906 respondents who answered questions about access to care, 9% were Black, 5% were Hispanic, and the rest were White. In these questions, differences between demographics arose when it came to individuals’ ability to conveniently see an MS specialist and their subsequent use of emergency services. For example, only 64% of Hispanic respondents reported convenient access to a health care provider specializing in MS, compared with 76% of White and 78% of Black respondents.
A significantly higher proportion of Hispanics also reported that they could not take time off from work when they were sick (25%) or to attend a doctor appointment (20%), compared with White (15% and 9%, respectively) and Black (18% and 12%) respondents. Meanwhile, a significantly higher proportion of Hispanics (35%) reported visiting the emergency department in the past year for MS-related issues, compared with White (19%) or Black (25%) respondents.
White respondents consistently had greater convenient access to dental offices, healthy foods, outpatient care, gyms, and parks and trails, compared with Black and Hispanic patients’ access. For example, 85% of White patients had convenient access to dental offices and 72% had access to outpatient care, compared with Black (74% and 65%) and Hispanic (78% and 52%) patients. Two-thirds of Hispanic respondents (67%) reported access to healthy foods and to gyms, parks, or trails, compared with more than three-quarters of both White and Black patients.
Other barriers to MS care
Both racial/ethnic and gender disparities emerged in how patients felt treated by their health care providers. Men were significantly more likely (70%) than women (65%) to say their health care provider listens to and understands them. A statistically significant higher proportion of men (71%) also said their clinician explained their MS test results to them, compared with women (62%), and only 28% of women, versus 37% of men, said their provider developed a long-term plan for them.
Anne Foelsch, the vice president of strategic partnerships at MyHealthTeam, who works with the authors, noted the large discrepancy that was seen particularly for Hispanic patients in terms of how they felt treated by their health care provider.
“Doctors might perceive that the relationship is the same with all of their patients when their patients have a very different perception of what that relationship is and whether they’re not being heard,” Ms. Foelsch said. “It’s important that clinicians take a little bit of time and learn a little bit more about a patient’s perspective and what it’s like when they have a chronic condition like MS and how it impacts their life, looking for those nuances that are different based on your ethnicity.”
Just over half of Hispanic patients (54%) said their provider explained their MS test results, compared with nearly two-thirds of White patients (65%) and 61% of Black patients. Hispanic patients were also less likely (55%) to say they felt their provider listens to and understands them than White (67%) or Black (65%) patients. Two-thirds of White respondents (67%) said their doctor recommended regular check-ups, compared with just over half of Black and Hispanic respondents (55%).
Other statistically significant disparities by race/ethnicity, where a higher proportion of White patients responded affirmatively than Black or Hispanic patients, included feeling treated with respect by their health care provider, feeling their provider is nonjudgmental, and saying their provider spends enough time with them, addresses their MS symptoms, and encourages shared decision-making.
“This study nicely documents and points out that despite our best intentions, we need to do much better as a community to help those with chronic and potentially disabling diseases like MS,” Dr. Gudesblatt said. “The racial, ethnic, and gender disparities only result in greater disability and societal costs by those who can least afford it. All therapies fail due to nonadherence, limited access, lack of insurance coverage, limited insurance coverage, high copays, long waits, cultural biases, and more.”
The researchers acknowledged that their survey respondents may not be representative of all patients with MS because the survey relied on those who chose to respond to the online survey.
The study authors were all employees of Publicis Health Media or MyHealthTeam. Dr. Gudesblatt reported no disclosures.
At CMSC 2023
Long-term freedom from NMOSD relapse with satralizumab
DENVER – , new research shows.
“In long-term observations, we are seeing a nice, sustained suppression of relapses early, as well as late, in treatment,” said study investigator Anthony Traboulsee, MD, University of British Columbia, Vancouver, in presenting the findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“It remains very tolerable with no participants discontinuing because of side effects,” he said. “And importantly, [there are] no signs of a delayed risk of infections for both monotherapy and combination therapy.”
Satralizumab, a monoclonal recycling antibody, targets the interleukin (IL)–6 receptor, which is elevated in the serum and cerebrospinal fluid of patients in NMOSD.
The drug was approved by the Food and Drug Administration in 2020 for the treatment of AQP4 antibody–positive NMOSD after favorable results from two key trials: SAkuraSky and SAkuraStar.
The FDA approval marked satralizumab as the third therapy for NMOSD, following eculizumab (Soliris) and inebilizumab (Uplizna).
Satralizumab is administered in subcutaneous injections every 4 weeks after a run-in period of injections at weeks 0, 2, and 4.
Longest trial to date
To evaluate the drug’s long-term efficacy in the treatment of AQP4 IgG–positive NMOSD, patients from the two previous phase 3 trials were entered into the single arm, open-label SAkuraMoon study and continued treatment with the satralizumab 120 mg injections once monthly, with or without immunosuppressive therapy.
The study included 106 patients (mean age 44 years, 89.6% women), all of whom had received one or more doses of satralizumab by the data cutoff of January 2022.
With a median duration of satralizumab exposure of 5 years, the overall adjusted annualized rate of investigator protocol-defined relapse (ARR) was 0.09.
Longitudinal assessment further showed no significant increase in the relapse rate over the course of the study, with an ARR rate of 0.16 at year 1; 0.10 at year 2; 0.05 at year 3; and 0.07 at year 4.
At week 240 (4.6 years), 72% of satralizumab-treated patients were relapse-free, with 91% free from severe relapse.
In addition, 85% of patients had no sustained disability, as measured by Expanded Disability Status Scale (EDSS) worsening, over the study period.
Asked if there are potential subgroups of patients who may be more susceptible to the worsening of disability, Dr. Traboulsee responded “not that we can tell as of yet.”
“I would like to explore this further as this is a relatively new observation, and, as far as I know, this is the longest follow-up for an NMO treatment trial cohort,” he said.
Favorable safety profile
The safety profile was also favorable, consistent with results in the earlier trials. The longer exposure to satralizumab was not associated with a higher risk of severe (grade 3 or higher) laboratory changes versus the double-blind studies. “Rates of adverse events and serious adverse events with overall satralizumab treatment were comparable with the double-blind periods,” said Dr. Traboulsee.
“With satralizumab combined with immunosuppressant therapy, we’re not seeing an increased rate of infections, because it’s not an immune suppressant – it doesn’t suppress lymphocytes or lower immunoglobulin,” he added.
While the use of combination therapy has been an important clinical concern, Dr. Traboulsee noted that “this does not appear to be the case with satralizumab when combined with daily prednisone or daily azathioprine.”
“There is no increased risk of infections, compared with placebo, and it interestingly appears lower than patients on prednisone or azathioprine alone,” he said.
While the median follow-up was 5 years, some in the clinical trial population have been on treatment for up to 7.9 years.
“Based on the current safety and efficacy data, they could stay on this therapy indefinitely, in my opinion,” Dr. Traboulsee said.
In addition to its long-term safety and efficacy, satralizumab “is easy for patients to take and does not require access to an infusion center. It’s easy for physicians to monitor safety, especially since no additional vaccinations or precautions are required beyond what is done in routine care.”
“What I conclude from that clinically is that this is a highly effective and safe therapy by itself or in combination with another agent,” Dr. Traboulsee said.
He noted that the lack of a bump in infections is “really encouraging and very important with a chronic disease that affects elderly patients. So far, so good,” he added.
‘A good first-line therapy’
Commenting on the study, Shailee Shah, MD, an assistant professor in the neuroimmunology division at Vanderbilt University Medical Center, Nashville, Tenn., agreed that the findings bode well for satralizumab’s long-term benefits.
“These are promising results and suggest that satralizumab is very effective in the long term, and even when patients relapse, those relapses are less severe than they would likely be if the patient were off therapy,” she said.
She noted that, while the ability to self-administer injections with satralizumab is convenient, preferences vary.
“This is patient dependent,” Dr. Shah said. “For some patients an injectable medication is ideal but for others an infusion medication [such as eculizumab] is preferred.”
Overall, however, Dr. Shah described satralizumab as “a good first-line therapy for patients with NMOSD in addition to eculizumab/ravulizumab and inebilizumab.”
“It is reasonable to consider this medication in isolation or with concomitant immunosuppressive therapy,” she said.
Dr. Traboulsee’s disclosures include relationships with Novartis, Roche, Sanofi (Genzyme), Ingo Kleiter, Alexion, Almirall, Bayer, Biogen, Celgene, Genentech, Hexal, Horizon, Merck, and Sanofi. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.
DENVER – , new research shows.
“In long-term observations, we are seeing a nice, sustained suppression of relapses early, as well as late, in treatment,” said study investigator Anthony Traboulsee, MD, University of British Columbia, Vancouver, in presenting the findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“It remains very tolerable with no participants discontinuing because of side effects,” he said. “And importantly, [there are] no signs of a delayed risk of infections for both monotherapy and combination therapy.”
Satralizumab, a monoclonal recycling antibody, targets the interleukin (IL)–6 receptor, which is elevated in the serum and cerebrospinal fluid of patients in NMOSD.
The drug was approved by the Food and Drug Administration in 2020 for the treatment of AQP4 antibody–positive NMOSD after favorable results from two key trials: SAkuraSky and SAkuraStar.
The FDA approval marked satralizumab as the third therapy for NMOSD, following eculizumab (Soliris) and inebilizumab (Uplizna).
Satralizumab is administered in subcutaneous injections every 4 weeks after a run-in period of injections at weeks 0, 2, and 4.
Longest trial to date
To evaluate the drug’s long-term efficacy in the treatment of AQP4 IgG–positive NMOSD, patients from the two previous phase 3 trials were entered into the single arm, open-label SAkuraMoon study and continued treatment with the satralizumab 120 mg injections once monthly, with or without immunosuppressive therapy.
The study included 106 patients (mean age 44 years, 89.6% women), all of whom had received one or more doses of satralizumab by the data cutoff of January 2022.
With a median duration of satralizumab exposure of 5 years, the overall adjusted annualized rate of investigator protocol-defined relapse (ARR) was 0.09.
Longitudinal assessment further showed no significant increase in the relapse rate over the course of the study, with an ARR rate of 0.16 at year 1; 0.10 at year 2; 0.05 at year 3; and 0.07 at year 4.
At week 240 (4.6 years), 72% of satralizumab-treated patients were relapse-free, with 91% free from severe relapse.
In addition, 85% of patients had no sustained disability, as measured by Expanded Disability Status Scale (EDSS) worsening, over the study period.
Asked if there are potential subgroups of patients who may be more susceptible to the worsening of disability, Dr. Traboulsee responded “not that we can tell as of yet.”
“I would like to explore this further as this is a relatively new observation, and, as far as I know, this is the longest follow-up for an NMO treatment trial cohort,” he said.
Favorable safety profile
The safety profile was also favorable, consistent with results in the earlier trials. The longer exposure to satralizumab was not associated with a higher risk of severe (grade 3 or higher) laboratory changes versus the double-blind studies. “Rates of adverse events and serious adverse events with overall satralizumab treatment were comparable with the double-blind periods,” said Dr. Traboulsee.
“With satralizumab combined with immunosuppressant therapy, we’re not seeing an increased rate of infections, because it’s not an immune suppressant – it doesn’t suppress lymphocytes or lower immunoglobulin,” he added.
While the use of combination therapy has been an important clinical concern, Dr. Traboulsee noted that “this does not appear to be the case with satralizumab when combined with daily prednisone or daily azathioprine.”
“There is no increased risk of infections, compared with placebo, and it interestingly appears lower than patients on prednisone or azathioprine alone,” he said.
While the median follow-up was 5 years, some in the clinical trial population have been on treatment for up to 7.9 years.
“Based on the current safety and efficacy data, they could stay on this therapy indefinitely, in my opinion,” Dr. Traboulsee said.
In addition to its long-term safety and efficacy, satralizumab “is easy for patients to take and does not require access to an infusion center. It’s easy for physicians to monitor safety, especially since no additional vaccinations or precautions are required beyond what is done in routine care.”
“What I conclude from that clinically is that this is a highly effective and safe therapy by itself or in combination with another agent,” Dr. Traboulsee said.
He noted that the lack of a bump in infections is “really encouraging and very important with a chronic disease that affects elderly patients. So far, so good,” he added.
‘A good first-line therapy’
Commenting on the study, Shailee Shah, MD, an assistant professor in the neuroimmunology division at Vanderbilt University Medical Center, Nashville, Tenn., agreed that the findings bode well for satralizumab’s long-term benefits.
“These are promising results and suggest that satralizumab is very effective in the long term, and even when patients relapse, those relapses are less severe than they would likely be if the patient were off therapy,” she said.
She noted that, while the ability to self-administer injections with satralizumab is convenient, preferences vary.
“This is patient dependent,” Dr. Shah said. “For some patients an injectable medication is ideal but for others an infusion medication [such as eculizumab] is preferred.”
Overall, however, Dr. Shah described satralizumab as “a good first-line therapy for patients with NMOSD in addition to eculizumab/ravulizumab and inebilizumab.”
“It is reasonable to consider this medication in isolation or with concomitant immunosuppressive therapy,” she said.
Dr. Traboulsee’s disclosures include relationships with Novartis, Roche, Sanofi (Genzyme), Ingo Kleiter, Alexion, Almirall, Bayer, Biogen, Celgene, Genentech, Hexal, Horizon, Merck, and Sanofi. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.
DENVER – , new research shows.
“In long-term observations, we are seeing a nice, sustained suppression of relapses early, as well as late, in treatment,” said study investigator Anthony Traboulsee, MD, University of British Columbia, Vancouver, in presenting the findings at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“It remains very tolerable with no participants discontinuing because of side effects,” he said. “And importantly, [there are] no signs of a delayed risk of infections for both monotherapy and combination therapy.”
Satralizumab, a monoclonal recycling antibody, targets the interleukin (IL)–6 receptor, which is elevated in the serum and cerebrospinal fluid of patients in NMOSD.
The drug was approved by the Food and Drug Administration in 2020 for the treatment of AQP4 antibody–positive NMOSD after favorable results from two key trials: SAkuraSky and SAkuraStar.
The FDA approval marked satralizumab as the third therapy for NMOSD, following eculizumab (Soliris) and inebilizumab (Uplizna).
Satralizumab is administered in subcutaneous injections every 4 weeks after a run-in period of injections at weeks 0, 2, and 4.
Longest trial to date
To evaluate the drug’s long-term efficacy in the treatment of AQP4 IgG–positive NMOSD, patients from the two previous phase 3 trials were entered into the single arm, open-label SAkuraMoon study and continued treatment with the satralizumab 120 mg injections once monthly, with or without immunosuppressive therapy.
The study included 106 patients (mean age 44 years, 89.6% women), all of whom had received one or more doses of satralizumab by the data cutoff of January 2022.
With a median duration of satralizumab exposure of 5 years, the overall adjusted annualized rate of investigator protocol-defined relapse (ARR) was 0.09.
Longitudinal assessment further showed no significant increase in the relapse rate over the course of the study, with an ARR rate of 0.16 at year 1; 0.10 at year 2; 0.05 at year 3; and 0.07 at year 4.
At week 240 (4.6 years), 72% of satralizumab-treated patients were relapse-free, with 91% free from severe relapse.
In addition, 85% of patients had no sustained disability, as measured by Expanded Disability Status Scale (EDSS) worsening, over the study period.
Asked if there are potential subgroups of patients who may be more susceptible to the worsening of disability, Dr. Traboulsee responded “not that we can tell as of yet.”
“I would like to explore this further as this is a relatively new observation, and, as far as I know, this is the longest follow-up for an NMO treatment trial cohort,” he said.
Favorable safety profile
The safety profile was also favorable, consistent with results in the earlier trials. The longer exposure to satralizumab was not associated with a higher risk of severe (grade 3 or higher) laboratory changes versus the double-blind studies. “Rates of adverse events and serious adverse events with overall satralizumab treatment were comparable with the double-blind periods,” said Dr. Traboulsee.
“With satralizumab combined with immunosuppressant therapy, we’re not seeing an increased rate of infections, because it’s not an immune suppressant – it doesn’t suppress lymphocytes or lower immunoglobulin,” he added.
While the use of combination therapy has been an important clinical concern, Dr. Traboulsee noted that “this does not appear to be the case with satralizumab when combined with daily prednisone or daily azathioprine.”
“There is no increased risk of infections, compared with placebo, and it interestingly appears lower than patients on prednisone or azathioprine alone,” he said.
While the median follow-up was 5 years, some in the clinical trial population have been on treatment for up to 7.9 years.
“Based on the current safety and efficacy data, they could stay on this therapy indefinitely, in my opinion,” Dr. Traboulsee said.
In addition to its long-term safety and efficacy, satralizumab “is easy for patients to take and does not require access to an infusion center. It’s easy for physicians to monitor safety, especially since no additional vaccinations or precautions are required beyond what is done in routine care.”
“What I conclude from that clinically is that this is a highly effective and safe therapy by itself or in combination with another agent,” Dr. Traboulsee said.
He noted that the lack of a bump in infections is “really encouraging and very important with a chronic disease that affects elderly patients. So far, so good,” he added.
‘A good first-line therapy’
Commenting on the study, Shailee Shah, MD, an assistant professor in the neuroimmunology division at Vanderbilt University Medical Center, Nashville, Tenn., agreed that the findings bode well for satralizumab’s long-term benefits.
“These are promising results and suggest that satralizumab is very effective in the long term, and even when patients relapse, those relapses are less severe than they would likely be if the patient were off therapy,” she said.
She noted that, while the ability to self-administer injections with satralizumab is convenient, preferences vary.
“This is patient dependent,” Dr. Shah said. “For some patients an injectable medication is ideal but for others an infusion medication [such as eculizumab] is preferred.”
Overall, however, Dr. Shah described satralizumab as “a good first-line therapy for patients with NMOSD in addition to eculizumab/ravulizumab and inebilizumab.”
“It is reasonable to consider this medication in isolation or with concomitant immunosuppressive therapy,” she said.
Dr. Traboulsee’s disclosures include relationships with Novartis, Roche, Sanofi (Genzyme), Ingo Kleiter, Alexion, Almirall, Bayer, Biogen, Celgene, Genentech, Hexal, Horizon, Merck, and Sanofi. Dr. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.
AT CMSC 2023
Mindfulness-based stress reduction program benefits MS patients
DENVER – The use of according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Two studies assessed the effects of two mindfulness-based stress reduction (MBSR) programs, one primarily in person until the pandemic forced a move to online participation, and the other exclusively online. The in-person course also found, in a subset of the participants, that blood inflammation markers matched the patients’ reported reduction in stress and loneliness.
Putting mindfulness to the test
Previous research has found that life stressors are linked to clinical MS flares, Chris Hemond, MD, an assistant professor of neurology at the University of Massachusetts, Worcester, told attendees. He also noted previous research exploring possible explanations for how MBSR programs might improve clinical symptoms of MS. One hypothesis involves an effect on the “forebrain limbic areas responsible for the neurobiological stress response.” Part of this study therefore involved looking for possible MRI changes before and after the MBSR program to test this hypothesis.
The study involved 23 patients, all women with relapsing remitting MS with an median age of 45, and 57% of whom were taking B cell–depleting agents. The patients’ average Expanded Disability Status Scale score was 2, and none experienced any new clinical or MRI disease activity during a 12-week observation period.
Patients volunteered to participate in the free 8-week MBSR program. Half attended MBSR classes in person while the other half had to attend virtual classes due to the pandemic. The program involved eight weekly 2.5-hour classes with daily homework assignments. The program, developed by Jon Kabat-Zinn at the University of Massachusetts, is intended to be “mental training for nonjudgmental awareness of moment-to-moment experience” that aims to “improve accuracy of perception, acceptance of intractable health-related changes, realistic sense of control, and appreciation of available life experiences,” Dr. Hemond said.
Among the 91% of participants who completed the course, 57% underwent both pre- and postcourse structural MRI scans, and 83% completed both the pre- and postcourse questionnaires. A subset of patients (53%) also provided blood samples for analysis of inflammatory gene expression markers.
“The conserved transcriptional response to adversity (CTRA) score was determined using well-established methods from 53 prespecified blood gene expression markers representing a composite of inflammation, interferon response, and immunoglobulin expression,” Dr. Hemond explained.
Participants’ average scores both pre- and post questionnaires revealed statistically significant improvements in stress, anxiety, depression, fatigue, loneliness, well-being, and interoceptive awareness (P < .01 for all).
Although precise values were not provided in the presentation, patients’ scores significantly decreased on the Brief Inventory of Perceived Stress (BIPS) for “lack of control,” “pushed,” and “conflict” (P < .03). Average scores also improved (decreased) on the Modified Fatigue Inventory Scale, the UCLA Loneliness Scale, and all three subscales of the Depression Anxiety Stress Scales assessment (P <.01). Participants’ scores increased on the Mental Health Continuum “hedonic” and “eudaimonic well-being” scales (P < .05).
Improvements on the Multidimensional Assessment of Interoceptive Awareness included self-regulation, attention regulation, “noticing” (P = .02), “not worrying” (P < .01), “emotional awareness” (P < .01), “body listening” (P < .01), and “trusting” (P < .01).
After adjustment for age, race, body mass index, medical therapy and time, the researchers found changes in inflammatory gene expression in the 12 participants who provided blood samples, and these changes correlated inversely with changes in their reported loneliness (P =.002), pain (P <.001), several interoception aspects (P < .01), and stress (P < .0001), particularly regarding feeling a lack of control.
Although no structural MRI changes were observed in the amygdala or prefrontal cortex, the researchers did see a 1% volume increase on the right-side hippocampus. Though the increase was significant (P < .01) and right hippocampal enlargement has been linked with MBSR in past studies, Dr. Hemond acknowledged the study’s small sample size and urged caution in interpreting that finding.
Dr. Hemond also reported that interaction between higher CTRA and the MSBR training attenuated the right hippocampal volume increase that was seen with MBSR, a finding which raises more questions than it answers.
The primary finding, however, was that “mindfulness-based stress reduction was associated with substantial improvement in multiple patient-reported outcomes of the debilitating ‘silent symptoms’ of MS,” Dr. Hemond told attendees. Though the study is limited by its small sample size, observational biases, and missing data, the findings suggest the possibility that MBSR is also associated with structural limbic brain changes, especially in the right hippocampus.
Another tool for managing MS
Ellen Mowry, MD, MCR, a professor of neurology and epidemiology at Johns Hopkins University, Baltimore, who attended the presentation, said she was very enthusiastic about this research.
“People with MS often are seeking ways that they can have self-efficacy and managing the symptoms of their disease, and we know that the disease-modifying therapies make a big difference, but we need additional therapies that can help people feel better and live better with MS,” Dr. Mowry commented.
She also acknowledged the challenges, however, in developing a mindfulness program that is accessible by a broad range of MS patients. This particular program involved several hours of work per day.
“People with MS often are either on the younger side, and they’re working and raising their family and doing all the same stuff that everybody else is doing, or they might be quite disabled and have more fatigue and other things that might make it really challenging to persist through that long of an intervention,” Dr. Mowry said.
The ideal program would be one that’s financially accessible, either through insurance, society more broadly, or another source, and which is logistically feasible for a wide range of patients. Finding a “sweet spot” with a program that doesn’t “require such a lengthy amount of time in order to see a success would be really great,” Dr. Mowry said. “You have to start somewhere, though, and you have to start with a program that’s already been tried and true and work from there.”
An online-only mindfulness program
One possible way to find that sweet spot is through an all-online program that patients access from home, similar to the 8-week MBSR program offered by Concord (N.H.) Hospital featured in the second study. The program was conducted via Zoom during once weekly synchronous meetings throughout 2021 and 2022 for eight cohorts of 5-15 participants each. The time of day the program was offered alternated between evening and daytime courses each quarter and was free for patients because of a hospital grant, according to Nicole Delcourt, BSN, RN, MSCN, of Concord Hospital Neurology, who facilitated patient sign-ups for the program.
Before and after each 8-week course, participants completed the PHQ-9, the PROMIS Cognitive Function, the PROMIS Fatigue–MS, and the Wasson Health Confidence assessments. Among the total 77 participating adults with MS, the completion rate was 81%, with 73% completing the preprogram assessments and 53% completed the postprogram assessments.
The assessments revealed a statistically significant increase in cognitive function and health confidence and decrease in depressive symptoms and fatigue following the program. Participants’ average PROMIS Cognitive Function scores increased from 16.7 before the program to 22.4 after, and their average Wasson Health Confidence score increased from 13.6 to 15.3 (P < .01 for both). Meanwhile, improvement in depressive symptoms was seen in participants’ decrease in Patient Health Questionnaire–9 scores from an average 6.9 to 4.6 (P = .01), and their average PROMIS Fatigue scores fell slightly but significantly from 59.3 to 55.3 (P < .05).
The participants “really felt like they were more in touch with their own feelings and emotions, and it helped them self-regulate,” Ms. Delcourt sad, “so it was really exciting.”
Patients also expressed satisfaction more subjectively in their feedback surveys. “I feel more aware of my body’s reactions to food and movement, and things that make me feel better physically,” one participant said. Another said that the class’s “lasting value ... will be to remember my own needs and how to become one with them.” Another participant praised the relevance of the printed and course materials, the speed of feedback on homework, and the quality of the video conference.
Dr. Hemond owns stock in VIVIO health. No other authors of either study reported other disclosures. Dr. Mowry has received grant funding from Biogen and Genentech. Ms. Delcourt had no disclosures. The in-person program study was funded by CMSC. Funding information for the Concord online program was unavailable.
DENVER – The use of according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Two studies assessed the effects of two mindfulness-based stress reduction (MBSR) programs, one primarily in person until the pandemic forced a move to online participation, and the other exclusively online. The in-person course also found, in a subset of the participants, that blood inflammation markers matched the patients’ reported reduction in stress and loneliness.
Putting mindfulness to the test
Previous research has found that life stressors are linked to clinical MS flares, Chris Hemond, MD, an assistant professor of neurology at the University of Massachusetts, Worcester, told attendees. He also noted previous research exploring possible explanations for how MBSR programs might improve clinical symptoms of MS. One hypothesis involves an effect on the “forebrain limbic areas responsible for the neurobiological stress response.” Part of this study therefore involved looking for possible MRI changes before and after the MBSR program to test this hypothesis.
The study involved 23 patients, all women with relapsing remitting MS with an median age of 45, and 57% of whom were taking B cell–depleting agents. The patients’ average Expanded Disability Status Scale score was 2, and none experienced any new clinical or MRI disease activity during a 12-week observation period.
Patients volunteered to participate in the free 8-week MBSR program. Half attended MBSR classes in person while the other half had to attend virtual classes due to the pandemic. The program involved eight weekly 2.5-hour classes with daily homework assignments. The program, developed by Jon Kabat-Zinn at the University of Massachusetts, is intended to be “mental training for nonjudgmental awareness of moment-to-moment experience” that aims to “improve accuracy of perception, acceptance of intractable health-related changes, realistic sense of control, and appreciation of available life experiences,” Dr. Hemond said.
Among the 91% of participants who completed the course, 57% underwent both pre- and postcourse structural MRI scans, and 83% completed both the pre- and postcourse questionnaires. A subset of patients (53%) also provided blood samples for analysis of inflammatory gene expression markers.
“The conserved transcriptional response to adversity (CTRA) score was determined using well-established methods from 53 prespecified blood gene expression markers representing a composite of inflammation, interferon response, and immunoglobulin expression,” Dr. Hemond explained.
Participants’ average scores both pre- and post questionnaires revealed statistically significant improvements in stress, anxiety, depression, fatigue, loneliness, well-being, and interoceptive awareness (P < .01 for all).
Although precise values were not provided in the presentation, patients’ scores significantly decreased on the Brief Inventory of Perceived Stress (BIPS) for “lack of control,” “pushed,” and “conflict” (P < .03). Average scores also improved (decreased) on the Modified Fatigue Inventory Scale, the UCLA Loneliness Scale, and all three subscales of the Depression Anxiety Stress Scales assessment (P <.01). Participants’ scores increased on the Mental Health Continuum “hedonic” and “eudaimonic well-being” scales (P < .05).
Improvements on the Multidimensional Assessment of Interoceptive Awareness included self-regulation, attention regulation, “noticing” (P = .02), “not worrying” (P < .01), “emotional awareness” (P < .01), “body listening” (P < .01), and “trusting” (P < .01).
After adjustment for age, race, body mass index, medical therapy and time, the researchers found changes in inflammatory gene expression in the 12 participants who provided blood samples, and these changes correlated inversely with changes in their reported loneliness (P =.002), pain (P <.001), several interoception aspects (P < .01), and stress (P < .0001), particularly regarding feeling a lack of control.
Although no structural MRI changes were observed in the amygdala or prefrontal cortex, the researchers did see a 1% volume increase on the right-side hippocampus. Though the increase was significant (P < .01) and right hippocampal enlargement has been linked with MBSR in past studies, Dr. Hemond acknowledged the study’s small sample size and urged caution in interpreting that finding.
Dr. Hemond also reported that interaction between higher CTRA and the MSBR training attenuated the right hippocampal volume increase that was seen with MBSR, a finding which raises more questions than it answers.
The primary finding, however, was that “mindfulness-based stress reduction was associated with substantial improvement in multiple patient-reported outcomes of the debilitating ‘silent symptoms’ of MS,” Dr. Hemond told attendees. Though the study is limited by its small sample size, observational biases, and missing data, the findings suggest the possibility that MBSR is also associated with structural limbic brain changes, especially in the right hippocampus.
Another tool for managing MS
Ellen Mowry, MD, MCR, a professor of neurology and epidemiology at Johns Hopkins University, Baltimore, who attended the presentation, said she was very enthusiastic about this research.
“People with MS often are seeking ways that they can have self-efficacy and managing the symptoms of their disease, and we know that the disease-modifying therapies make a big difference, but we need additional therapies that can help people feel better and live better with MS,” Dr. Mowry commented.
She also acknowledged the challenges, however, in developing a mindfulness program that is accessible by a broad range of MS patients. This particular program involved several hours of work per day.
“People with MS often are either on the younger side, and they’re working and raising their family and doing all the same stuff that everybody else is doing, or they might be quite disabled and have more fatigue and other things that might make it really challenging to persist through that long of an intervention,” Dr. Mowry said.
The ideal program would be one that’s financially accessible, either through insurance, society more broadly, or another source, and which is logistically feasible for a wide range of patients. Finding a “sweet spot” with a program that doesn’t “require such a lengthy amount of time in order to see a success would be really great,” Dr. Mowry said. “You have to start somewhere, though, and you have to start with a program that’s already been tried and true and work from there.”
An online-only mindfulness program
One possible way to find that sweet spot is through an all-online program that patients access from home, similar to the 8-week MBSR program offered by Concord (N.H.) Hospital featured in the second study. The program was conducted via Zoom during once weekly synchronous meetings throughout 2021 and 2022 for eight cohorts of 5-15 participants each. The time of day the program was offered alternated between evening and daytime courses each quarter and was free for patients because of a hospital grant, according to Nicole Delcourt, BSN, RN, MSCN, of Concord Hospital Neurology, who facilitated patient sign-ups for the program.
Before and after each 8-week course, participants completed the PHQ-9, the PROMIS Cognitive Function, the PROMIS Fatigue–MS, and the Wasson Health Confidence assessments. Among the total 77 participating adults with MS, the completion rate was 81%, with 73% completing the preprogram assessments and 53% completed the postprogram assessments.
The assessments revealed a statistically significant increase in cognitive function and health confidence and decrease in depressive symptoms and fatigue following the program. Participants’ average PROMIS Cognitive Function scores increased from 16.7 before the program to 22.4 after, and their average Wasson Health Confidence score increased from 13.6 to 15.3 (P < .01 for both). Meanwhile, improvement in depressive symptoms was seen in participants’ decrease in Patient Health Questionnaire–9 scores from an average 6.9 to 4.6 (P = .01), and their average PROMIS Fatigue scores fell slightly but significantly from 59.3 to 55.3 (P < .05).
The participants “really felt like they were more in touch with their own feelings and emotions, and it helped them self-regulate,” Ms. Delcourt sad, “so it was really exciting.”
Patients also expressed satisfaction more subjectively in their feedback surveys. “I feel more aware of my body’s reactions to food and movement, and things that make me feel better physically,” one participant said. Another said that the class’s “lasting value ... will be to remember my own needs and how to become one with them.” Another participant praised the relevance of the printed and course materials, the speed of feedback on homework, and the quality of the video conference.
Dr. Hemond owns stock in VIVIO health. No other authors of either study reported other disclosures. Dr. Mowry has received grant funding from Biogen and Genentech. Ms. Delcourt had no disclosures. The in-person program study was funded by CMSC. Funding information for the Concord online program was unavailable.
DENVER – The use of according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Two studies assessed the effects of two mindfulness-based stress reduction (MBSR) programs, one primarily in person until the pandemic forced a move to online participation, and the other exclusively online. The in-person course also found, in a subset of the participants, that blood inflammation markers matched the patients’ reported reduction in stress and loneliness.
Putting mindfulness to the test
Previous research has found that life stressors are linked to clinical MS flares, Chris Hemond, MD, an assistant professor of neurology at the University of Massachusetts, Worcester, told attendees. He also noted previous research exploring possible explanations for how MBSR programs might improve clinical symptoms of MS. One hypothesis involves an effect on the “forebrain limbic areas responsible for the neurobiological stress response.” Part of this study therefore involved looking for possible MRI changes before and after the MBSR program to test this hypothesis.
The study involved 23 patients, all women with relapsing remitting MS with an median age of 45, and 57% of whom were taking B cell–depleting agents. The patients’ average Expanded Disability Status Scale score was 2, and none experienced any new clinical or MRI disease activity during a 12-week observation period.
Patients volunteered to participate in the free 8-week MBSR program. Half attended MBSR classes in person while the other half had to attend virtual classes due to the pandemic. The program involved eight weekly 2.5-hour classes with daily homework assignments. The program, developed by Jon Kabat-Zinn at the University of Massachusetts, is intended to be “mental training for nonjudgmental awareness of moment-to-moment experience” that aims to “improve accuracy of perception, acceptance of intractable health-related changes, realistic sense of control, and appreciation of available life experiences,” Dr. Hemond said.
Among the 91% of participants who completed the course, 57% underwent both pre- and postcourse structural MRI scans, and 83% completed both the pre- and postcourse questionnaires. A subset of patients (53%) also provided blood samples for analysis of inflammatory gene expression markers.
“The conserved transcriptional response to adversity (CTRA) score was determined using well-established methods from 53 prespecified blood gene expression markers representing a composite of inflammation, interferon response, and immunoglobulin expression,” Dr. Hemond explained.
Participants’ average scores both pre- and post questionnaires revealed statistically significant improvements in stress, anxiety, depression, fatigue, loneliness, well-being, and interoceptive awareness (P < .01 for all).
Although precise values were not provided in the presentation, patients’ scores significantly decreased on the Brief Inventory of Perceived Stress (BIPS) for “lack of control,” “pushed,” and “conflict” (P < .03). Average scores also improved (decreased) on the Modified Fatigue Inventory Scale, the UCLA Loneliness Scale, and all three subscales of the Depression Anxiety Stress Scales assessment (P <.01). Participants’ scores increased on the Mental Health Continuum “hedonic” and “eudaimonic well-being” scales (P < .05).
Improvements on the Multidimensional Assessment of Interoceptive Awareness included self-regulation, attention regulation, “noticing” (P = .02), “not worrying” (P < .01), “emotional awareness” (P < .01), “body listening” (P < .01), and “trusting” (P < .01).
After adjustment for age, race, body mass index, medical therapy and time, the researchers found changes in inflammatory gene expression in the 12 participants who provided blood samples, and these changes correlated inversely with changes in their reported loneliness (P =.002), pain (P <.001), several interoception aspects (P < .01), and stress (P < .0001), particularly regarding feeling a lack of control.
Although no structural MRI changes were observed in the amygdala or prefrontal cortex, the researchers did see a 1% volume increase on the right-side hippocampus. Though the increase was significant (P < .01) and right hippocampal enlargement has been linked with MBSR in past studies, Dr. Hemond acknowledged the study’s small sample size and urged caution in interpreting that finding.
Dr. Hemond also reported that interaction between higher CTRA and the MSBR training attenuated the right hippocampal volume increase that was seen with MBSR, a finding which raises more questions than it answers.
The primary finding, however, was that “mindfulness-based stress reduction was associated with substantial improvement in multiple patient-reported outcomes of the debilitating ‘silent symptoms’ of MS,” Dr. Hemond told attendees. Though the study is limited by its small sample size, observational biases, and missing data, the findings suggest the possibility that MBSR is also associated with structural limbic brain changes, especially in the right hippocampus.
Another tool for managing MS
Ellen Mowry, MD, MCR, a professor of neurology and epidemiology at Johns Hopkins University, Baltimore, who attended the presentation, said she was very enthusiastic about this research.
“People with MS often are seeking ways that they can have self-efficacy and managing the symptoms of their disease, and we know that the disease-modifying therapies make a big difference, but we need additional therapies that can help people feel better and live better with MS,” Dr. Mowry commented.
She also acknowledged the challenges, however, in developing a mindfulness program that is accessible by a broad range of MS patients. This particular program involved several hours of work per day.
“People with MS often are either on the younger side, and they’re working and raising their family and doing all the same stuff that everybody else is doing, or they might be quite disabled and have more fatigue and other things that might make it really challenging to persist through that long of an intervention,” Dr. Mowry said.
The ideal program would be one that’s financially accessible, either through insurance, society more broadly, or another source, and which is logistically feasible for a wide range of patients. Finding a “sweet spot” with a program that doesn’t “require such a lengthy amount of time in order to see a success would be really great,” Dr. Mowry said. “You have to start somewhere, though, and you have to start with a program that’s already been tried and true and work from there.”
An online-only mindfulness program
One possible way to find that sweet spot is through an all-online program that patients access from home, similar to the 8-week MBSR program offered by Concord (N.H.) Hospital featured in the second study. The program was conducted via Zoom during once weekly synchronous meetings throughout 2021 and 2022 for eight cohorts of 5-15 participants each. The time of day the program was offered alternated between evening and daytime courses each quarter and was free for patients because of a hospital grant, according to Nicole Delcourt, BSN, RN, MSCN, of Concord Hospital Neurology, who facilitated patient sign-ups for the program.
Before and after each 8-week course, participants completed the PHQ-9, the PROMIS Cognitive Function, the PROMIS Fatigue–MS, and the Wasson Health Confidence assessments. Among the total 77 participating adults with MS, the completion rate was 81%, with 73% completing the preprogram assessments and 53% completed the postprogram assessments.
The assessments revealed a statistically significant increase in cognitive function and health confidence and decrease in depressive symptoms and fatigue following the program. Participants’ average PROMIS Cognitive Function scores increased from 16.7 before the program to 22.4 after, and their average Wasson Health Confidence score increased from 13.6 to 15.3 (P < .01 for both). Meanwhile, improvement in depressive symptoms was seen in participants’ decrease in Patient Health Questionnaire–9 scores from an average 6.9 to 4.6 (P = .01), and their average PROMIS Fatigue scores fell slightly but significantly from 59.3 to 55.3 (P < .05).
The participants “really felt like they were more in touch with their own feelings and emotions, and it helped them self-regulate,” Ms. Delcourt sad, “so it was really exciting.”
Patients also expressed satisfaction more subjectively in their feedback surveys. “I feel more aware of my body’s reactions to food and movement, and things that make me feel better physically,” one participant said. Another said that the class’s “lasting value ... will be to remember my own needs and how to become one with them.” Another participant praised the relevance of the printed and course materials, the speed of feedback on homework, and the quality of the video conference.
Dr. Hemond owns stock in VIVIO health. No other authors of either study reported other disclosures. Dr. Mowry has received grant funding from Biogen and Genentech. Ms. Delcourt had no disclosures. The in-person program study was funded by CMSC. Funding information for the Concord online program was unavailable.
AT CMSC 2023
Stem cell transplants are more effective than some MS therapies
, data indicate.
In a multicenter study that emulated pairwise trials, AHSCT was associated with a higher likelihood of disability improvement, compared with fingolimod (hazard ratio, 2.70).
Once the immune system is reconstituted, it can contribute to the healing process. AHSCT thus provides the possibility of improvement in MS. Disease-modifying therapies that require continued use, however, could inhibit that process.
“If you can stop the inflammation that’s driving this disease fairly early on, [patients] do have the capacity to repair,” said study author Mark Freedman, MD, a professor of neurology at the University of Ottawa. “And we start to see that especially in a treatment [like AHSCT] where you don’t maintain the hit on the immune system.”
The study was published online in JAMA Neurology.
Pairwise analyses
Single-arm studies and an open-label, randomized trial have suggested that AHSCT has efficacy. The regimen is associated with a 0.3%-2.0% risk for mortality, but this risk has declined with better patient selection and clinical experience, according to the researchers. Comparative studies of AHSCT and DMTs are needed, but they are difficult to carry out, which is why the current team chose a propensity-score matched case–control design, according to lead author Tomas Kalincik, MD, PhD, head of the University of Melbourne’s Clinical Outcomes Research Unit.
The researchers examined data from 4,915 patients with relapsing-remitting MS. Of this population, 3.4% received AHSCT, 52.0% received fingolimod, 30.3% received natalizumab, and 14.2% received ocrelizumab. The proportion of women in the treatment groups ranged from 65% to 70%.
The researchers used pairwise matching to simulate the randomized, controlled trials comparing AHSCT with fingolimod, natalizumab, and ocrelizumab. Patients were matched on the basis of sex, age, disability, relapse events at 12 and 24 months before baseline, time from first symptoms to baseline, the most effective previous DMT, and geographical region.
Compared with fingolimod, AHSCT was associated with fewer relapses (annualized relapse rate, 0.09 vs. 0.20; P < .001). This finding was confirmed by a reduced cumulative hazard of relapse (HR, 0.26).
Compared with natalizumab, AHSCT had only a modestly greater effect on annualized relapse rates (ARR, 0.08 vs. 0.10; P = .03), with a cumulative HR for relapses of 0.51.
There was no significant difference in the risk for relapse between treatment with AHSCT and with ocrelizumab (ARR, 0.09 vs. 0.06; P = .86), nor was the risk of cumulative relapses significantly different between these treatments.
Among patients included in the pairwise analyses who received AHSCT, 23.3% developed febrile neutropenia during mobilization, 11.3% developed serum sickness, and 8.8% were admitted to an intensive care unit. There were 82 serious adverse events among 58 patients after they were discharged post AHSCT treatment, including infections (59.8% of adverse events) that were primarily due to viral sources (41.5% of adverse events). There was one death (0.6%) due to veno-occlusive disease of the liver following busulfan exposure.
Some AHSCT protocols are stronger than others, and milder immune ablative measures are less likely to produce lasting effects. “We completely remove the old immune system and put in a brand new one,” said Dr. Freedman, referring to the practice at his center. “That’s a fairly horrendous procedure, and, not surprisingly, we’ve had a slight increase in the types of side effects, compared with other groups who don’t use that heavy-duty conditioning regimen, but we’ve had absolutely zero return of inflammatory events over 23 years that we’ve been doing this. Nobody’s had another attack, no one has even developed a single new MRI lesion.”
The so-called medium and light conditioning regimens are associated with a return of disease activity in about 25% of patients within 3 years, Dr. Freedman added. “You start to see new MRI lesions form and relapses occurring. It’s still better than any of the higher efficacy therapies, but it’s not stopped the disease.”
A key limitation of the study is that its efficacy analysis did not distinguish between different intensities of AHSCT regimens, according to the authors.
Encouraging results
AHSCT is highly effective at temporarily eliminating inflammation in the central nervous system, according to Jeffrey Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, and Anne Cross, MD, professor of neurology at Washington University, St. Louis, who wrote an editorial that accompanied the study. As many as 35% of patients require DMTs at some point after AHSCT.
The results of the new study are encouraging, but plenty of unanswered questions remain, Dr. Cohen said. “Many studies demonstrate AHSCT to have potent durable efficacy that appears to be greater than that of the available DMTs, but some studies – for example, this one – suggest that AHSCT may be superior to some but not all DMTs. Therefore, where to place AHSCT in the overall treatment sequence remains uncertain.” Randomized, controlled trials that are now in process “hopefully will clarify,” he added.
The study was supported by the National Health and Medical Research Council of Australia, Multiple Sclerosis Australia, and the MS Foundation of Canada. Dr. Kalincik has financial relationships with Eisai, Novartis, Biogen, Merck, Roche, Sanofi Genzyme, Teva, Celgene, Bristol-Myers Squibb, and Janssen. Dr. Freedman has financial relationships with Sanofi-Genzyme Canada, Alexion, Atara Biotherapeutics, Bayer Healthcare, Beigene, BMS (Celgene), EMD, Hoffmann-La Roche, Janssen, Merck Serono, Quanterix, Novartis, Sanofi-Genzyme, Teva Canada Innovation, Celestra Health, McKesson, and EMD Serono. Dr. Cohen has financial relationships with Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI.
A version of this article first appeared on Medscape.com.
, data indicate.
In a multicenter study that emulated pairwise trials, AHSCT was associated with a higher likelihood of disability improvement, compared with fingolimod (hazard ratio, 2.70).
Once the immune system is reconstituted, it can contribute to the healing process. AHSCT thus provides the possibility of improvement in MS. Disease-modifying therapies that require continued use, however, could inhibit that process.
“If you can stop the inflammation that’s driving this disease fairly early on, [patients] do have the capacity to repair,” said study author Mark Freedman, MD, a professor of neurology at the University of Ottawa. “And we start to see that especially in a treatment [like AHSCT] where you don’t maintain the hit on the immune system.”
The study was published online in JAMA Neurology.
Pairwise analyses
Single-arm studies and an open-label, randomized trial have suggested that AHSCT has efficacy. The regimen is associated with a 0.3%-2.0% risk for mortality, but this risk has declined with better patient selection and clinical experience, according to the researchers. Comparative studies of AHSCT and DMTs are needed, but they are difficult to carry out, which is why the current team chose a propensity-score matched case–control design, according to lead author Tomas Kalincik, MD, PhD, head of the University of Melbourne’s Clinical Outcomes Research Unit.
The researchers examined data from 4,915 patients with relapsing-remitting MS. Of this population, 3.4% received AHSCT, 52.0% received fingolimod, 30.3% received natalizumab, and 14.2% received ocrelizumab. The proportion of women in the treatment groups ranged from 65% to 70%.
The researchers used pairwise matching to simulate the randomized, controlled trials comparing AHSCT with fingolimod, natalizumab, and ocrelizumab. Patients were matched on the basis of sex, age, disability, relapse events at 12 and 24 months before baseline, time from first symptoms to baseline, the most effective previous DMT, and geographical region.
Compared with fingolimod, AHSCT was associated with fewer relapses (annualized relapse rate, 0.09 vs. 0.20; P < .001). This finding was confirmed by a reduced cumulative hazard of relapse (HR, 0.26).
Compared with natalizumab, AHSCT had only a modestly greater effect on annualized relapse rates (ARR, 0.08 vs. 0.10; P = .03), with a cumulative HR for relapses of 0.51.
There was no significant difference in the risk for relapse between treatment with AHSCT and with ocrelizumab (ARR, 0.09 vs. 0.06; P = .86), nor was the risk of cumulative relapses significantly different between these treatments.
Among patients included in the pairwise analyses who received AHSCT, 23.3% developed febrile neutropenia during mobilization, 11.3% developed serum sickness, and 8.8% were admitted to an intensive care unit. There were 82 serious adverse events among 58 patients after they were discharged post AHSCT treatment, including infections (59.8% of adverse events) that were primarily due to viral sources (41.5% of adverse events). There was one death (0.6%) due to veno-occlusive disease of the liver following busulfan exposure.
Some AHSCT protocols are stronger than others, and milder immune ablative measures are less likely to produce lasting effects. “We completely remove the old immune system and put in a brand new one,” said Dr. Freedman, referring to the practice at his center. “That’s a fairly horrendous procedure, and, not surprisingly, we’ve had a slight increase in the types of side effects, compared with other groups who don’t use that heavy-duty conditioning regimen, but we’ve had absolutely zero return of inflammatory events over 23 years that we’ve been doing this. Nobody’s had another attack, no one has even developed a single new MRI lesion.”
The so-called medium and light conditioning regimens are associated with a return of disease activity in about 25% of patients within 3 years, Dr. Freedman added. “You start to see new MRI lesions form and relapses occurring. It’s still better than any of the higher efficacy therapies, but it’s not stopped the disease.”
A key limitation of the study is that its efficacy analysis did not distinguish between different intensities of AHSCT regimens, according to the authors.
Encouraging results
AHSCT is highly effective at temporarily eliminating inflammation in the central nervous system, according to Jeffrey Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, and Anne Cross, MD, professor of neurology at Washington University, St. Louis, who wrote an editorial that accompanied the study. As many as 35% of patients require DMTs at some point after AHSCT.
The results of the new study are encouraging, but plenty of unanswered questions remain, Dr. Cohen said. “Many studies demonstrate AHSCT to have potent durable efficacy that appears to be greater than that of the available DMTs, but some studies – for example, this one – suggest that AHSCT may be superior to some but not all DMTs. Therefore, where to place AHSCT in the overall treatment sequence remains uncertain.” Randomized, controlled trials that are now in process “hopefully will clarify,” he added.
The study was supported by the National Health and Medical Research Council of Australia, Multiple Sclerosis Australia, and the MS Foundation of Canada. Dr. Kalincik has financial relationships with Eisai, Novartis, Biogen, Merck, Roche, Sanofi Genzyme, Teva, Celgene, Bristol-Myers Squibb, and Janssen. Dr. Freedman has financial relationships with Sanofi-Genzyme Canada, Alexion, Atara Biotherapeutics, Bayer Healthcare, Beigene, BMS (Celgene), EMD, Hoffmann-La Roche, Janssen, Merck Serono, Quanterix, Novartis, Sanofi-Genzyme, Teva Canada Innovation, Celestra Health, McKesson, and EMD Serono. Dr. Cohen has financial relationships with Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI.
A version of this article first appeared on Medscape.com.
, data indicate.
In a multicenter study that emulated pairwise trials, AHSCT was associated with a higher likelihood of disability improvement, compared with fingolimod (hazard ratio, 2.70).
Once the immune system is reconstituted, it can contribute to the healing process. AHSCT thus provides the possibility of improvement in MS. Disease-modifying therapies that require continued use, however, could inhibit that process.
“If you can stop the inflammation that’s driving this disease fairly early on, [patients] do have the capacity to repair,” said study author Mark Freedman, MD, a professor of neurology at the University of Ottawa. “And we start to see that especially in a treatment [like AHSCT] where you don’t maintain the hit on the immune system.”
The study was published online in JAMA Neurology.
Pairwise analyses
Single-arm studies and an open-label, randomized trial have suggested that AHSCT has efficacy. The regimen is associated with a 0.3%-2.0% risk for mortality, but this risk has declined with better patient selection and clinical experience, according to the researchers. Comparative studies of AHSCT and DMTs are needed, but they are difficult to carry out, which is why the current team chose a propensity-score matched case–control design, according to lead author Tomas Kalincik, MD, PhD, head of the University of Melbourne’s Clinical Outcomes Research Unit.
The researchers examined data from 4,915 patients with relapsing-remitting MS. Of this population, 3.4% received AHSCT, 52.0% received fingolimod, 30.3% received natalizumab, and 14.2% received ocrelizumab. The proportion of women in the treatment groups ranged from 65% to 70%.
The researchers used pairwise matching to simulate the randomized, controlled trials comparing AHSCT with fingolimod, natalizumab, and ocrelizumab. Patients were matched on the basis of sex, age, disability, relapse events at 12 and 24 months before baseline, time from first symptoms to baseline, the most effective previous DMT, and geographical region.
Compared with fingolimod, AHSCT was associated with fewer relapses (annualized relapse rate, 0.09 vs. 0.20; P < .001). This finding was confirmed by a reduced cumulative hazard of relapse (HR, 0.26).
Compared with natalizumab, AHSCT had only a modestly greater effect on annualized relapse rates (ARR, 0.08 vs. 0.10; P = .03), with a cumulative HR for relapses of 0.51.
There was no significant difference in the risk for relapse between treatment with AHSCT and with ocrelizumab (ARR, 0.09 vs. 0.06; P = .86), nor was the risk of cumulative relapses significantly different between these treatments.
Among patients included in the pairwise analyses who received AHSCT, 23.3% developed febrile neutropenia during mobilization, 11.3% developed serum sickness, and 8.8% were admitted to an intensive care unit. There were 82 serious adverse events among 58 patients after they were discharged post AHSCT treatment, including infections (59.8% of adverse events) that were primarily due to viral sources (41.5% of adverse events). There was one death (0.6%) due to veno-occlusive disease of the liver following busulfan exposure.
Some AHSCT protocols are stronger than others, and milder immune ablative measures are less likely to produce lasting effects. “We completely remove the old immune system and put in a brand new one,” said Dr. Freedman, referring to the practice at his center. “That’s a fairly horrendous procedure, and, not surprisingly, we’ve had a slight increase in the types of side effects, compared with other groups who don’t use that heavy-duty conditioning regimen, but we’ve had absolutely zero return of inflammatory events over 23 years that we’ve been doing this. Nobody’s had another attack, no one has even developed a single new MRI lesion.”
The so-called medium and light conditioning regimens are associated with a return of disease activity in about 25% of patients within 3 years, Dr. Freedman added. “You start to see new MRI lesions form and relapses occurring. It’s still better than any of the higher efficacy therapies, but it’s not stopped the disease.”
A key limitation of the study is that its efficacy analysis did not distinguish between different intensities of AHSCT regimens, according to the authors.
Encouraging results
AHSCT is highly effective at temporarily eliminating inflammation in the central nervous system, according to Jeffrey Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, and Anne Cross, MD, professor of neurology at Washington University, St. Louis, who wrote an editorial that accompanied the study. As many as 35% of patients require DMTs at some point after AHSCT.
The results of the new study are encouraging, but plenty of unanswered questions remain, Dr. Cohen said. “Many studies demonstrate AHSCT to have potent durable efficacy that appears to be greater than that of the available DMTs, but some studies – for example, this one – suggest that AHSCT may be superior to some but not all DMTs. Therefore, where to place AHSCT in the overall treatment sequence remains uncertain.” Randomized, controlled trials that are now in process “hopefully will clarify,” he added.
The study was supported by the National Health and Medical Research Council of Australia, Multiple Sclerosis Australia, and the MS Foundation of Canada. Dr. Kalincik has financial relationships with Eisai, Novartis, Biogen, Merck, Roche, Sanofi Genzyme, Teva, Celgene, Bristol-Myers Squibb, and Janssen. Dr. Freedman has financial relationships with Sanofi-Genzyme Canada, Alexion, Atara Biotherapeutics, Bayer Healthcare, Beigene, BMS (Celgene), EMD, Hoffmann-La Roche, Janssen, Merck Serono, Quanterix, Novartis, Sanofi-Genzyme, Teva Canada Innovation, Celestra Health, McKesson, and EMD Serono. Dr. Cohen has financial relationships with Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
Teriflunomide delays MS symptoms in radiologically isolated syndrome
BOSTON – , according to a double-blind, phase 3 trial presented in the Emerging Science session of the 2023 annual meeting of the American Academy of Neurology.
“These data add to the evidence that early immunomodulation offers clinical benefit even in the presymptomatic phase of MS,” reported Christine Lebrun-Frenay, MD, PhD, head of inflammatory neurological disorders research unit, University of Nice, France. This is the second study to show a benefit from a disease-modifying therapy in asymptomatic RIS patients. The ARISE study, which was presented at the 2022 European Committee for Treatment and Research in MS and has now been published, compared 240 mg of twice-daily dimethyl fumarate with placebo. Dimethyl fumarate was associated with an 82% (hazard ratio, 0.18; P = .007) reduction in the risk of a first demyelinating event after 96 weeks of follow-up.
TERIS trial data
In the new study, called TERIS, the design and outcomes were similar to the ARISE study. Eighty-nine patients meeting standard criteria for RIS were randomized to 14 mg of once-daily teriflunomide or placebo. The majority (71%) were female, and the mean age was 39.8 years. At the time of RIS diagnosis, the mean age was 38 years. At study entry, standardized MRI studies were performed of the brain and spinal cord.
During 2 years of follow-up, 8 of 28 demyelinating events were observed in the active treatment group. The remaining 20 occurred in the placebo group. This translated to a 63% reduction (HR, 0.37; P = .018) in favor of teriflunomide. When graphed, the curves separated at about 6 months and then widened progressively over time.
Distinct from clinically isolated syndrome (CIS), which describes individuals who have a symptomatic episode consistent with a demyelinating event, RIS is based primarily on an MRI that shows lesions highly suggestive of MS. Neither confirms the MS diagnosis, but both are associated with a high likelihood of eventually meeting MS diagnostic criteria. The ARISE and TERIS studies now support therapy to delay demyelinating events.
“With more and more people having brain scans for various reasons, such as headache or head trauma, more of these cases are being discovered,” Dr. Lebrun-Frenay said.
Caution warranted when interpreting the findings
The data support the theory that treatment should begin early in patients with a high likelihood of developing symptomatic MS on the basis of brain lesions. It is logical to assume that preventing damage to the myelin will reduce or delay permanent symptoms and permanent neurologic impairment, but Dr. Lebrun-Frenay suggested that the available data from ARISE and TERIS are not practice changing even though both were multicenter double-blind trials.
“More data from larger groups of patients are needed to confirm the findings,” she said. She expressed concern about not adhering to strict criteria to diagnosis RIS.
“It is important that medical professionals are cautious,” she said, citing the risk of misdiagnosis of pathology of MRI that leads to treatment of patients with a low risk of developing symptomatic MS.
Teriflunomide and dimethyl fumarate, which have long been available as first-line therapies in relapsing-remitting MS, are generally well tolerated. In the TERIS and ARISE studies, mild or moderate events occurred more commonly in the active treatment than the placebo arms, but there were no serious adverse events. However, both can produce more serious adverse events, which, in the case of teriflunomide, include liver toxicity leading to injury and liver failure.
Challenging the traditional definition of MS
The author of the ARISE study, Darin T. Okuda, MD, a professor of neurology at the UT Southwestern Medical Center, Dallas, indicated that his study, now reinforced by the TERIS study, challenges the definition of MS.
“Both ARISE and TERIS demonstrated a significant reduction in seminal clinical event rates related to inflammatory demyelination,” Dr. Okuda said in an interview. They provide evidence that patients are at high risk of the demyelinating events that characterize MS. Given the potential difficulty for accessing therapies of benefit, “how we define multiple sclerosis is highly important.”
“Individuals of younger age with abnormal spinal cord MRI studies along with other paraclinical features related to risk for a first event may be the most ideal group to treat,” he said. However, he agreed with Dr. Lebrun-Frenay that it is not yet clear which RIS patients are the most appropriate candidates.
“Gaining a more refined sense of who we should treat will require more work,” he said.
These data are likely to change the orientation toward RIS, according to Melina Hosseiny, MD, department of radiology, University of California, Los Angeles, Medical Center. She noted that the relationship between RIS and increased risk of MS has long been recognized, and the risk increases with specific features on imaging.
“Studies have shown that spinal cord lesions are associated with a greater than 50% chance of converting to MS,” said Dr. Hosseiny, who was the lead author of a review article on RIS. “Identifying such imaging findings can help identify patients who may benefit from disease-modifying medications.”
Dr. Lebrun-Frenay reports no potential conflicts of interest. Dr. Okuda has financial relationships with Alexion, Biogen, Celgene, EMD Serono, Genzyme, TG Therapeutics, and VielaBio. Dr. Hosseiny reports no potential conflicts of interest.
BOSTON – , according to a double-blind, phase 3 trial presented in the Emerging Science session of the 2023 annual meeting of the American Academy of Neurology.
“These data add to the evidence that early immunomodulation offers clinical benefit even in the presymptomatic phase of MS,” reported Christine Lebrun-Frenay, MD, PhD, head of inflammatory neurological disorders research unit, University of Nice, France. This is the second study to show a benefit from a disease-modifying therapy in asymptomatic RIS patients. The ARISE study, which was presented at the 2022 European Committee for Treatment and Research in MS and has now been published, compared 240 mg of twice-daily dimethyl fumarate with placebo. Dimethyl fumarate was associated with an 82% (hazard ratio, 0.18; P = .007) reduction in the risk of a first demyelinating event after 96 weeks of follow-up.
TERIS trial data
In the new study, called TERIS, the design and outcomes were similar to the ARISE study. Eighty-nine patients meeting standard criteria for RIS were randomized to 14 mg of once-daily teriflunomide or placebo. The majority (71%) were female, and the mean age was 39.8 years. At the time of RIS diagnosis, the mean age was 38 years. At study entry, standardized MRI studies were performed of the brain and spinal cord.
During 2 years of follow-up, 8 of 28 demyelinating events were observed in the active treatment group. The remaining 20 occurred in the placebo group. This translated to a 63% reduction (HR, 0.37; P = .018) in favor of teriflunomide. When graphed, the curves separated at about 6 months and then widened progressively over time.
Distinct from clinically isolated syndrome (CIS), which describes individuals who have a symptomatic episode consistent with a demyelinating event, RIS is based primarily on an MRI that shows lesions highly suggestive of MS. Neither confirms the MS diagnosis, but both are associated with a high likelihood of eventually meeting MS diagnostic criteria. The ARISE and TERIS studies now support therapy to delay demyelinating events.
“With more and more people having brain scans for various reasons, such as headache or head trauma, more of these cases are being discovered,” Dr. Lebrun-Frenay said.
Caution warranted when interpreting the findings
The data support the theory that treatment should begin early in patients with a high likelihood of developing symptomatic MS on the basis of brain lesions. It is logical to assume that preventing damage to the myelin will reduce or delay permanent symptoms and permanent neurologic impairment, but Dr. Lebrun-Frenay suggested that the available data from ARISE and TERIS are not practice changing even though both were multicenter double-blind trials.
“More data from larger groups of patients are needed to confirm the findings,” she said. She expressed concern about not adhering to strict criteria to diagnosis RIS.
“It is important that medical professionals are cautious,” she said, citing the risk of misdiagnosis of pathology of MRI that leads to treatment of patients with a low risk of developing symptomatic MS.
Teriflunomide and dimethyl fumarate, which have long been available as first-line therapies in relapsing-remitting MS, are generally well tolerated. In the TERIS and ARISE studies, mild or moderate events occurred more commonly in the active treatment than the placebo arms, but there were no serious adverse events. However, both can produce more serious adverse events, which, in the case of teriflunomide, include liver toxicity leading to injury and liver failure.
Challenging the traditional definition of MS
The author of the ARISE study, Darin T. Okuda, MD, a professor of neurology at the UT Southwestern Medical Center, Dallas, indicated that his study, now reinforced by the TERIS study, challenges the definition of MS.
“Both ARISE and TERIS demonstrated a significant reduction in seminal clinical event rates related to inflammatory demyelination,” Dr. Okuda said in an interview. They provide evidence that patients are at high risk of the demyelinating events that characterize MS. Given the potential difficulty for accessing therapies of benefit, “how we define multiple sclerosis is highly important.”
“Individuals of younger age with abnormal spinal cord MRI studies along with other paraclinical features related to risk for a first event may be the most ideal group to treat,” he said. However, he agreed with Dr. Lebrun-Frenay that it is not yet clear which RIS patients are the most appropriate candidates.
“Gaining a more refined sense of who we should treat will require more work,” he said.
These data are likely to change the orientation toward RIS, according to Melina Hosseiny, MD, department of radiology, University of California, Los Angeles, Medical Center. She noted that the relationship between RIS and increased risk of MS has long been recognized, and the risk increases with specific features on imaging.
“Studies have shown that spinal cord lesions are associated with a greater than 50% chance of converting to MS,” said Dr. Hosseiny, who was the lead author of a review article on RIS. “Identifying such imaging findings can help identify patients who may benefit from disease-modifying medications.”
Dr. Lebrun-Frenay reports no potential conflicts of interest. Dr. Okuda has financial relationships with Alexion, Biogen, Celgene, EMD Serono, Genzyme, TG Therapeutics, and VielaBio. Dr. Hosseiny reports no potential conflicts of interest.
BOSTON – , according to a double-blind, phase 3 trial presented in the Emerging Science session of the 2023 annual meeting of the American Academy of Neurology.
“These data add to the evidence that early immunomodulation offers clinical benefit even in the presymptomatic phase of MS,” reported Christine Lebrun-Frenay, MD, PhD, head of inflammatory neurological disorders research unit, University of Nice, France. This is the second study to show a benefit from a disease-modifying therapy in asymptomatic RIS patients. The ARISE study, which was presented at the 2022 European Committee for Treatment and Research in MS and has now been published, compared 240 mg of twice-daily dimethyl fumarate with placebo. Dimethyl fumarate was associated with an 82% (hazard ratio, 0.18; P = .007) reduction in the risk of a first demyelinating event after 96 weeks of follow-up.
TERIS trial data
In the new study, called TERIS, the design and outcomes were similar to the ARISE study. Eighty-nine patients meeting standard criteria for RIS were randomized to 14 mg of once-daily teriflunomide or placebo. The majority (71%) were female, and the mean age was 39.8 years. At the time of RIS diagnosis, the mean age was 38 years. At study entry, standardized MRI studies were performed of the brain and spinal cord.
During 2 years of follow-up, 8 of 28 demyelinating events were observed in the active treatment group. The remaining 20 occurred in the placebo group. This translated to a 63% reduction (HR, 0.37; P = .018) in favor of teriflunomide. When graphed, the curves separated at about 6 months and then widened progressively over time.
Distinct from clinically isolated syndrome (CIS), which describes individuals who have a symptomatic episode consistent with a demyelinating event, RIS is based primarily on an MRI that shows lesions highly suggestive of MS. Neither confirms the MS diagnosis, but both are associated with a high likelihood of eventually meeting MS diagnostic criteria. The ARISE and TERIS studies now support therapy to delay demyelinating events.
“With more and more people having brain scans for various reasons, such as headache or head trauma, more of these cases are being discovered,” Dr. Lebrun-Frenay said.
Caution warranted when interpreting the findings
The data support the theory that treatment should begin early in patients with a high likelihood of developing symptomatic MS on the basis of brain lesions. It is logical to assume that preventing damage to the myelin will reduce or delay permanent symptoms and permanent neurologic impairment, but Dr. Lebrun-Frenay suggested that the available data from ARISE and TERIS are not practice changing even though both were multicenter double-blind trials.
“More data from larger groups of patients are needed to confirm the findings,” she said. She expressed concern about not adhering to strict criteria to diagnosis RIS.
“It is important that medical professionals are cautious,” she said, citing the risk of misdiagnosis of pathology of MRI that leads to treatment of patients with a low risk of developing symptomatic MS.
Teriflunomide and dimethyl fumarate, which have long been available as first-line therapies in relapsing-remitting MS, are generally well tolerated. In the TERIS and ARISE studies, mild or moderate events occurred more commonly in the active treatment than the placebo arms, but there were no serious adverse events. However, both can produce more serious adverse events, which, in the case of teriflunomide, include liver toxicity leading to injury and liver failure.
Challenging the traditional definition of MS
The author of the ARISE study, Darin T. Okuda, MD, a professor of neurology at the UT Southwestern Medical Center, Dallas, indicated that his study, now reinforced by the TERIS study, challenges the definition of MS.
“Both ARISE and TERIS demonstrated a significant reduction in seminal clinical event rates related to inflammatory demyelination,” Dr. Okuda said in an interview. They provide evidence that patients are at high risk of the demyelinating events that characterize MS. Given the potential difficulty for accessing therapies of benefit, “how we define multiple sclerosis is highly important.”
“Individuals of younger age with abnormal spinal cord MRI studies along with other paraclinical features related to risk for a first event may be the most ideal group to treat,” he said. However, he agreed with Dr. Lebrun-Frenay that it is not yet clear which RIS patients are the most appropriate candidates.
“Gaining a more refined sense of who we should treat will require more work,” he said.
These data are likely to change the orientation toward RIS, according to Melina Hosseiny, MD, department of radiology, University of California, Los Angeles, Medical Center. She noted that the relationship between RIS and increased risk of MS has long been recognized, and the risk increases with specific features on imaging.
“Studies have shown that spinal cord lesions are associated with a greater than 50% chance of converting to MS,” said Dr. Hosseiny, who was the lead author of a review article on RIS. “Identifying such imaging findings can help identify patients who may benefit from disease-modifying medications.”
Dr. Lebrun-Frenay reports no potential conflicts of interest. Dr. Okuda has financial relationships with Alexion, Biogen, Celgene, EMD Serono, Genzyme, TG Therapeutics, and VielaBio. Dr. Hosseiny reports no potential conflicts of interest.
AT AAN 2023
High-dose vitamin D and MS relapse: New phase 3 data
, results from a randomized control trial show. However, at least one expert believes the study’s exclusion criteria may have been too broad.
The investigation of vitamin D to prevent relapse of MS is based on older observational studies of people who already had higher blood levels of vitamin D and were less likely to develop MS, said study investigator Ellen Mowry, MD, Richard T. and Frances W. Johnson professor of neurology, Johns Hopkins University, Baltimore.
Later research where participants were given vitamin D as a therapeutic option for MS “were disappointing as the vitamin D had minimal effect,” she said.
“While we were excited by early data suggesting that vitamin D may have an important impact on MS, it’s essential to follow those linkage studies with the gold standard clinical evidence, which we have here,” Dr. Mowry added.
The findings were published online in eClinicalMedicine.
No difference in relapse risk
The multisite, phase 3 Vitamin D to Ameliorate MS (VIDAMS) clinical trial included 172 participants aged 18-50 years with RRMS from 16 neurology clinics between 2012 and 2019.
Inclusion criteria were having one or more clinical episodes of MS in the past year and at least one brain lesion on MRI in the past year or having two or more clinical episodes in the past year. Eligible participants also had to have a score of 4 or less on the Kurtzke Expanded Disability Status Scale.
A total of 83 participants were randomly assigned to receive low-dose vitamin D3 (600 IU/day) and 89 to receive high-dose vitamin D3 (5,000 IU/day). Each participant took the vitamin tablet with glatiramer acetate, a synthetic protein that simulates myelin.
Participants were assessed every 12 weeks to measure serum 25(OH)D levels and every 24 weeks for a number of movement and coordination tests, as well as two 3T clinical brain MRIs to check for lesions.
By the trial’s end at 96 weeks, the researchers found no differences in relapse risk between the high- and low-dose groups (P = .57). In addition, there were no differences in MRI outcomes between the two groups.
Dr. Mowry said that more than a few people have asked her if she is disappointed by the results of the VIDAMS trial. “I tell them that no, I’m not – that we are scientists and clinicians, and it is our job to understand what they can do to fight their disease. And if the answer is not vitamin D, that’s OK – we have many other ideas.”
These include helping patients minimize cardiometabolic comorbidities, such as heart disease and blood pressure, she said.
Exclusion criteria too broad?
Commenting on the findings, Alberto Ascherio, MD, professor of epidemiology and nutrition at Harvard School of Public Health, Boston, said a key principle of recommending vitamin supplements is that they are, generally speaking, only beneficial for individuals with vitamin deficiencies.
He noted that “patients with vitamin D deficiency (25(OH)D < 15 ng/mL, which corresponds to 37.5 nmol/L) were excluded from this study. Most importantly, the baseline mean 25(OH)D levels were about 30 ng/mL (75 nmol/L), which is considered a sufficient level (the IOM considers 20 ng/mL = 50 nmol/L as an adequate level),” with the level further increasing during the trial due to the supplementation.
“It would be a serious mistake to conclude from this trial (or any of the previous trials) that vitamin D supplementation is not important in MS patients,” Dr. Ascherio said.
He added that many individuals with MS have serum vitamin D levels below 20 ng/mL (50 nmol/L) and that this was the median serum value in studies among individuals with MS in Europe.
“These patients would almost certainly benefit from moderate doses of vitamin D supplements or judicious UV light exposure. Most likely even patients with sufficient but suboptimal 25(OH)D levels (between 20 and 30 ng/mL, or 50 and 75 nmol/L) would benefit from an increase,” he said.
The study was funded by the National Multiple Sclerosis Society, Teva Neuroscience, and the National Institute of Health. Dr. Mowry reported grant support from the National MS Society, Biogen, Genentech, and Teva Neuroscience; honoraria from UpToDate; and consulting fees from BeCare Link.
A version of this article first appeared on Medscape.com.
, results from a randomized control trial show. However, at least one expert believes the study’s exclusion criteria may have been too broad.
The investigation of vitamin D to prevent relapse of MS is based on older observational studies of people who already had higher blood levels of vitamin D and were less likely to develop MS, said study investigator Ellen Mowry, MD, Richard T. and Frances W. Johnson professor of neurology, Johns Hopkins University, Baltimore.
Later research where participants were given vitamin D as a therapeutic option for MS “were disappointing as the vitamin D had minimal effect,” she said.
“While we were excited by early data suggesting that vitamin D may have an important impact on MS, it’s essential to follow those linkage studies with the gold standard clinical evidence, which we have here,” Dr. Mowry added.
The findings were published online in eClinicalMedicine.
No difference in relapse risk
The multisite, phase 3 Vitamin D to Ameliorate MS (VIDAMS) clinical trial included 172 participants aged 18-50 years with RRMS from 16 neurology clinics between 2012 and 2019.
Inclusion criteria were having one or more clinical episodes of MS in the past year and at least one brain lesion on MRI in the past year or having two or more clinical episodes in the past year. Eligible participants also had to have a score of 4 or less on the Kurtzke Expanded Disability Status Scale.
A total of 83 participants were randomly assigned to receive low-dose vitamin D3 (600 IU/day) and 89 to receive high-dose vitamin D3 (5,000 IU/day). Each participant took the vitamin tablet with glatiramer acetate, a synthetic protein that simulates myelin.
Participants were assessed every 12 weeks to measure serum 25(OH)D levels and every 24 weeks for a number of movement and coordination tests, as well as two 3T clinical brain MRIs to check for lesions.
By the trial’s end at 96 weeks, the researchers found no differences in relapse risk between the high- and low-dose groups (P = .57). In addition, there were no differences in MRI outcomes between the two groups.
Dr. Mowry said that more than a few people have asked her if she is disappointed by the results of the VIDAMS trial. “I tell them that no, I’m not – that we are scientists and clinicians, and it is our job to understand what they can do to fight their disease. And if the answer is not vitamin D, that’s OK – we have many other ideas.”
These include helping patients minimize cardiometabolic comorbidities, such as heart disease and blood pressure, she said.
Exclusion criteria too broad?
Commenting on the findings, Alberto Ascherio, MD, professor of epidemiology and nutrition at Harvard School of Public Health, Boston, said a key principle of recommending vitamin supplements is that they are, generally speaking, only beneficial for individuals with vitamin deficiencies.
He noted that “patients with vitamin D deficiency (25(OH)D < 15 ng/mL, which corresponds to 37.5 nmol/L) were excluded from this study. Most importantly, the baseline mean 25(OH)D levels were about 30 ng/mL (75 nmol/L), which is considered a sufficient level (the IOM considers 20 ng/mL = 50 nmol/L as an adequate level),” with the level further increasing during the trial due to the supplementation.
“It would be a serious mistake to conclude from this trial (or any of the previous trials) that vitamin D supplementation is not important in MS patients,” Dr. Ascherio said.
He added that many individuals with MS have serum vitamin D levels below 20 ng/mL (50 nmol/L) and that this was the median serum value in studies among individuals with MS in Europe.
“These patients would almost certainly benefit from moderate doses of vitamin D supplements or judicious UV light exposure. Most likely even patients with sufficient but suboptimal 25(OH)D levels (between 20 and 30 ng/mL, or 50 and 75 nmol/L) would benefit from an increase,” he said.
The study was funded by the National Multiple Sclerosis Society, Teva Neuroscience, and the National Institute of Health. Dr. Mowry reported grant support from the National MS Society, Biogen, Genentech, and Teva Neuroscience; honoraria from UpToDate; and consulting fees from BeCare Link.
A version of this article first appeared on Medscape.com.
, results from a randomized control trial show. However, at least one expert believes the study’s exclusion criteria may have been too broad.
The investigation of vitamin D to prevent relapse of MS is based on older observational studies of people who already had higher blood levels of vitamin D and were less likely to develop MS, said study investigator Ellen Mowry, MD, Richard T. and Frances W. Johnson professor of neurology, Johns Hopkins University, Baltimore.
Later research where participants were given vitamin D as a therapeutic option for MS “were disappointing as the vitamin D had minimal effect,” she said.
“While we were excited by early data suggesting that vitamin D may have an important impact on MS, it’s essential to follow those linkage studies with the gold standard clinical evidence, which we have here,” Dr. Mowry added.
The findings were published online in eClinicalMedicine.
No difference in relapse risk
The multisite, phase 3 Vitamin D to Ameliorate MS (VIDAMS) clinical trial included 172 participants aged 18-50 years with RRMS from 16 neurology clinics between 2012 and 2019.
Inclusion criteria were having one or more clinical episodes of MS in the past year and at least one brain lesion on MRI in the past year or having two or more clinical episodes in the past year. Eligible participants also had to have a score of 4 or less on the Kurtzke Expanded Disability Status Scale.
A total of 83 participants were randomly assigned to receive low-dose vitamin D3 (600 IU/day) and 89 to receive high-dose vitamin D3 (5,000 IU/day). Each participant took the vitamin tablet with glatiramer acetate, a synthetic protein that simulates myelin.
Participants were assessed every 12 weeks to measure serum 25(OH)D levels and every 24 weeks for a number of movement and coordination tests, as well as two 3T clinical brain MRIs to check for lesions.
By the trial’s end at 96 weeks, the researchers found no differences in relapse risk between the high- and low-dose groups (P = .57). In addition, there were no differences in MRI outcomes between the two groups.
Dr. Mowry said that more than a few people have asked her if she is disappointed by the results of the VIDAMS trial. “I tell them that no, I’m not – that we are scientists and clinicians, and it is our job to understand what they can do to fight their disease. And if the answer is not vitamin D, that’s OK – we have many other ideas.”
These include helping patients minimize cardiometabolic comorbidities, such as heart disease and blood pressure, she said.
Exclusion criteria too broad?
Commenting on the findings, Alberto Ascherio, MD, professor of epidemiology and nutrition at Harvard School of Public Health, Boston, said a key principle of recommending vitamin supplements is that they are, generally speaking, only beneficial for individuals with vitamin deficiencies.
He noted that “patients with vitamin D deficiency (25(OH)D < 15 ng/mL, which corresponds to 37.5 nmol/L) were excluded from this study. Most importantly, the baseline mean 25(OH)D levels were about 30 ng/mL (75 nmol/L), which is considered a sufficient level (the IOM considers 20 ng/mL = 50 nmol/L as an adequate level),” with the level further increasing during the trial due to the supplementation.
“It would be a serious mistake to conclude from this trial (or any of the previous trials) that vitamin D supplementation is not important in MS patients,” Dr. Ascherio said.
He added that many individuals with MS have serum vitamin D levels below 20 ng/mL (50 nmol/L) and that this was the median serum value in studies among individuals with MS in Europe.
“These patients would almost certainly benefit from moderate doses of vitamin D supplements or judicious UV light exposure. Most likely even patients with sufficient but suboptimal 25(OH)D levels (between 20 and 30 ng/mL, or 50 and 75 nmol/L) would benefit from an increase,” he said.
The study was funded by the National Multiple Sclerosis Society, Teva Neuroscience, and the National Institute of Health. Dr. Mowry reported grant support from the National MS Society, Biogen, Genentech, and Teva Neuroscience; honoraria from UpToDate; and consulting fees from BeCare Link.
A version of this article first appeared on Medscape.com.
FROM ECLINICALMEDICINE
Machine learning can predict primary progressive MS progression
BOSTON – , according to a proof-of-concept study presented at the 2023 annual meeting of the American Academy of Neurology.
The accuracy was sufficient for the lead author of the study, Michael Gurevich, PhD, head of the Neuroimmunological Laboratory in the Multiple Sclerosis Center of Sheba Medical Center in Ramat Gan, Israel, to say that it is already clinically viable even as the tool is still evolving.
“We are looking at larger sample sizes to improve the accuracy and generalizability of our model, but we can use it now to inform treatment decisions,” Dr. Gurevich said.
In patients with PPMS who have a highly variable course, the model predicts disability progression with an accuracy of approximately 70%, according to the data he presented. He said he believes this is already at a level that it is meaningful for a risk-to-benefit calculation when considering treatment.
Machine learning analyzes blood samples
The study pursues the concept that the genetic information governing highly complex pathophysiological processes is contained in RNA sequencing. While multimodal omics generate data that are too complex for human pattern recognition, there is a growing body of evidence, including that provided by this study, to suggest that machine learning can employ these same RNA profiles and predict disease activity.
In this study, blood samples were collected from patients who participated in the phase 3 clinical ORATORIO trial that led to approval of ocrelizumab for PPMS. Analyses were conducted only on blood samples from those randomized to placebo, who, like those in the active treatment arm, were evaluated at baseline and at 12-week intervals for more than 2 years.
After development of a prediction model and creation of a training dataset, machine learning was applied to the deep sequencing of the blood transcriptome data for predicting two endpoints. One was disease progression at 120 weeks defined as a 1 point or more increase in the Expanded Disability Status Scale (EDSS) among patients with confirmed disability progression for at least 12 weeks (12W-CDP).
The other was change at 120 weeks in brain morphology defined as a 1% or more reduction in brain volume (120W PBVC).
The peripheral blood samples were subjected to RNA sequencing analysis (RNA-Seq) using commercially available analysis techniques. The prediction model for the disability endpoint was based on data generated from the blood transcriptome of 135 patients of which 53 (39%) met the endpoint at 120 weeks. The prediction model for the change in brain morphology was based on the blood transcriptome from 94 patients of which 63 (67%) met the endpoint.
On the basis of 10 genes that most significantly differentiated those who met the disability endpoint from those who did not, machine recognition of patterns after training was able to predict correctly the outcome in 70.9%. The sensitivity was 55.6%, and the specificity was 79.0%. The positive and negative predictive values were 59.0% and 76.8%, respectively.
On the basis of the 12 genes the most significantly differentiated those that reached the 120W PBVC endpoint from those who did not, machine learning resulted in a correct prediction of outcomes in 75.1%. The sensitivity was 78.1%, and the specificity was 66.7%. The positive and negative predictive values were 83.3% and 58.8%, respectively
Typical of a PPMS trial population, the mean age of the patients was about 44 years. The mean disease duration was about 6 years. The majority of patients had an EDSS score below 5.5 at baseline. The baseline T2 lesion number was approximately 50.
If further validated by others and in larger studies, this type of information could play a valuable role in PPMS management, according to Dr. Gurevich. Now that there is an approved therapy for PPMS, it can help clinicians and patients determine whether to initiate treatment early to address the high risk of progression or delay treatment that might not be needed.
A useful tool
In the field of MS, most of the studies performed with machine learning have focused on the analysis of radiological images. However, others are now looking at the blood transcriptome as a potential path to better classifying a highly complex disease with substantial heterogeneity in presentation, progression, and outcome.
For example, machine learning of the blood transcriptome has also shown high accuracy in the diagnosis and classification of MS in patients with clinically isolated syndrome (CIS). One study, published in Cell Reports Medicine, was led by Cinthia Farina, PhD, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan.
Although she did not hear the presentation by Dr. Gurevich, Dr. Farina is enthusiastic about the potential for machine learning to help manage MS through the analysis of the blood transcriptome. “I do believe that transcriptomics in peripheral immune cells may become a useful tool for MS diagnosis and prognosis,” she said.
In her own study, in which machine learning algorithms were developed and trained on the basis of peripheral blood from patients with CIS, the tool proved accurate with a strong potential for being incorporated into routine clinical management.
“Machine learning applied to the blood transcriptomes was extremely efficient with a 95.6% accuracy in discriminating PPMS from RRMS [relapsing-remitting] MS,” she reported.
Dr. Gurevich has no potential financial conflicts of interest to report. He reported funding for the study was provided by Roche. Dr. Farina reports financial relationships with Merck-Serono, Novartis, and Teva.
BOSTON – , according to a proof-of-concept study presented at the 2023 annual meeting of the American Academy of Neurology.
The accuracy was sufficient for the lead author of the study, Michael Gurevich, PhD, head of the Neuroimmunological Laboratory in the Multiple Sclerosis Center of Sheba Medical Center in Ramat Gan, Israel, to say that it is already clinically viable even as the tool is still evolving.
“We are looking at larger sample sizes to improve the accuracy and generalizability of our model, but we can use it now to inform treatment decisions,” Dr. Gurevich said.
In patients with PPMS who have a highly variable course, the model predicts disability progression with an accuracy of approximately 70%, according to the data he presented. He said he believes this is already at a level that it is meaningful for a risk-to-benefit calculation when considering treatment.
Machine learning analyzes blood samples
The study pursues the concept that the genetic information governing highly complex pathophysiological processes is contained in RNA sequencing. While multimodal omics generate data that are too complex for human pattern recognition, there is a growing body of evidence, including that provided by this study, to suggest that machine learning can employ these same RNA profiles and predict disease activity.
In this study, blood samples were collected from patients who participated in the phase 3 clinical ORATORIO trial that led to approval of ocrelizumab for PPMS. Analyses were conducted only on blood samples from those randomized to placebo, who, like those in the active treatment arm, were evaluated at baseline and at 12-week intervals for more than 2 years.
After development of a prediction model and creation of a training dataset, machine learning was applied to the deep sequencing of the blood transcriptome data for predicting two endpoints. One was disease progression at 120 weeks defined as a 1 point or more increase in the Expanded Disability Status Scale (EDSS) among patients with confirmed disability progression for at least 12 weeks (12W-CDP).
The other was change at 120 weeks in brain morphology defined as a 1% or more reduction in brain volume (120W PBVC).
The peripheral blood samples were subjected to RNA sequencing analysis (RNA-Seq) using commercially available analysis techniques. The prediction model for the disability endpoint was based on data generated from the blood transcriptome of 135 patients of which 53 (39%) met the endpoint at 120 weeks. The prediction model for the change in brain morphology was based on the blood transcriptome from 94 patients of which 63 (67%) met the endpoint.
On the basis of 10 genes that most significantly differentiated those who met the disability endpoint from those who did not, machine recognition of patterns after training was able to predict correctly the outcome in 70.9%. The sensitivity was 55.6%, and the specificity was 79.0%. The positive and negative predictive values were 59.0% and 76.8%, respectively.
On the basis of the 12 genes the most significantly differentiated those that reached the 120W PBVC endpoint from those who did not, machine learning resulted in a correct prediction of outcomes in 75.1%. The sensitivity was 78.1%, and the specificity was 66.7%. The positive and negative predictive values were 83.3% and 58.8%, respectively
Typical of a PPMS trial population, the mean age of the patients was about 44 years. The mean disease duration was about 6 years. The majority of patients had an EDSS score below 5.5 at baseline. The baseline T2 lesion number was approximately 50.
If further validated by others and in larger studies, this type of information could play a valuable role in PPMS management, according to Dr. Gurevich. Now that there is an approved therapy for PPMS, it can help clinicians and patients determine whether to initiate treatment early to address the high risk of progression or delay treatment that might not be needed.
A useful tool
In the field of MS, most of the studies performed with machine learning have focused on the analysis of radiological images. However, others are now looking at the blood transcriptome as a potential path to better classifying a highly complex disease with substantial heterogeneity in presentation, progression, and outcome.
For example, machine learning of the blood transcriptome has also shown high accuracy in the diagnosis and classification of MS in patients with clinically isolated syndrome (CIS). One study, published in Cell Reports Medicine, was led by Cinthia Farina, PhD, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan.
Although she did not hear the presentation by Dr. Gurevich, Dr. Farina is enthusiastic about the potential for machine learning to help manage MS through the analysis of the blood transcriptome. “I do believe that transcriptomics in peripheral immune cells may become a useful tool for MS diagnosis and prognosis,” she said.
In her own study, in which machine learning algorithms were developed and trained on the basis of peripheral blood from patients with CIS, the tool proved accurate with a strong potential for being incorporated into routine clinical management.
“Machine learning applied to the blood transcriptomes was extremely efficient with a 95.6% accuracy in discriminating PPMS from RRMS [relapsing-remitting] MS,” she reported.
Dr. Gurevich has no potential financial conflicts of interest to report. He reported funding for the study was provided by Roche. Dr. Farina reports financial relationships with Merck-Serono, Novartis, and Teva.
BOSTON – , according to a proof-of-concept study presented at the 2023 annual meeting of the American Academy of Neurology.
The accuracy was sufficient for the lead author of the study, Michael Gurevich, PhD, head of the Neuroimmunological Laboratory in the Multiple Sclerosis Center of Sheba Medical Center in Ramat Gan, Israel, to say that it is already clinically viable even as the tool is still evolving.
“We are looking at larger sample sizes to improve the accuracy and generalizability of our model, but we can use it now to inform treatment decisions,” Dr. Gurevich said.
In patients with PPMS who have a highly variable course, the model predicts disability progression with an accuracy of approximately 70%, according to the data he presented. He said he believes this is already at a level that it is meaningful for a risk-to-benefit calculation when considering treatment.
Machine learning analyzes blood samples
The study pursues the concept that the genetic information governing highly complex pathophysiological processes is contained in RNA sequencing. While multimodal omics generate data that are too complex for human pattern recognition, there is a growing body of evidence, including that provided by this study, to suggest that machine learning can employ these same RNA profiles and predict disease activity.
In this study, blood samples were collected from patients who participated in the phase 3 clinical ORATORIO trial that led to approval of ocrelizumab for PPMS. Analyses were conducted only on blood samples from those randomized to placebo, who, like those in the active treatment arm, were evaluated at baseline and at 12-week intervals for more than 2 years.
After development of a prediction model and creation of a training dataset, machine learning was applied to the deep sequencing of the blood transcriptome data for predicting two endpoints. One was disease progression at 120 weeks defined as a 1 point or more increase in the Expanded Disability Status Scale (EDSS) among patients with confirmed disability progression for at least 12 weeks (12W-CDP).
The other was change at 120 weeks in brain morphology defined as a 1% or more reduction in brain volume (120W PBVC).
The peripheral blood samples were subjected to RNA sequencing analysis (RNA-Seq) using commercially available analysis techniques. The prediction model for the disability endpoint was based on data generated from the blood transcriptome of 135 patients of which 53 (39%) met the endpoint at 120 weeks. The prediction model for the change in brain morphology was based on the blood transcriptome from 94 patients of which 63 (67%) met the endpoint.
On the basis of 10 genes that most significantly differentiated those who met the disability endpoint from those who did not, machine recognition of patterns after training was able to predict correctly the outcome in 70.9%. The sensitivity was 55.6%, and the specificity was 79.0%. The positive and negative predictive values were 59.0% and 76.8%, respectively.
On the basis of the 12 genes the most significantly differentiated those that reached the 120W PBVC endpoint from those who did not, machine learning resulted in a correct prediction of outcomes in 75.1%. The sensitivity was 78.1%, and the specificity was 66.7%. The positive and negative predictive values were 83.3% and 58.8%, respectively
Typical of a PPMS trial population, the mean age of the patients was about 44 years. The mean disease duration was about 6 years. The majority of patients had an EDSS score below 5.5 at baseline. The baseline T2 lesion number was approximately 50.
If further validated by others and in larger studies, this type of information could play a valuable role in PPMS management, according to Dr. Gurevich. Now that there is an approved therapy for PPMS, it can help clinicians and patients determine whether to initiate treatment early to address the high risk of progression or delay treatment that might not be needed.
A useful tool
In the field of MS, most of the studies performed with machine learning have focused on the analysis of radiological images. However, others are now looking at the blood transcriptome as a potential path to better classifying a highly complex disease with substantial heterogeneity in presentation, progression, and outcome.
For example, machine learning of the blood transcriptome has also shown high accuracy in the diagnosis and classification of MS in patients with clinically isolated syndrome (CIS). One study, published in Cell Reports Medicine, was led by Cinthia Farina, PhD, Institute of Experimental Neurology, IRCCS San Raffaele Scientific Institute, Milan.
Although she did not hear the presentation by Dr. Gurevich, Dr. Farina is enthusiastic about the potential for machine learning to help manage MS through the analysis of the blood transcriptome. “I do believe that transcriptomics in peripheral immune cells may become a useful tool for MS diagnosis and prognosis,” she said.
In her own study, in which machine learning algorithms were developed and trained on the basis of peripheral blood from patients with CIS, the tool proved accurate with a strong potential for being incorporated into routine clinical management.
“Machine learning applied to the blood transcriptomes was extremely efficient with a 95.6% accuracy in discriminating PPMS from RRMS [relapsing-remitting] MS,” she reported.
Dr. Gurevich has no potential financial conflicts of interest to report. He reported funding for the study was provided by Roche. Dr. Farina reports financial relationships with Merck-Serono, Novartis, and Teva.
FROM AAN 2023
Raising Awareness for Managing Disease-Modifying Therapies in Aging Persons With Multiple Sclerosis
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and neurodegenerative disease that affects the central nervous system. While there is no cure for MS, significant progress has been made during the last 2 decades, with over 25 medications developed, including disease modifying therapies (DMTs) that have shown benefit in reducing the number of acute events (relapses), curbing the development of new lesions seen on magnetic resonance imaging (MRI), and slowing disease progression/worsening. However, the benefit of available DMTs is seen primarily during the inflammatory stage of the disease (relapsing remitting) and is less clear in the later stages (secondary-progressive disease). Age was shown to be one of the most consistent contributing factors linked to disease worsening, and most studies suggest limited benefit of available DMTs in patients older than 50 years.
Meanwhile, the aging MS population is increasing worldwide, with most patients being between ages 55 and 65 years—a trend considered related to a general extended life expectancy, better diagnosis, early initiation of efficient DMTs, and improved general medical care. As persons with MS (pwMS) age, there is a clear change in the clinical presentation, with reduced risk for relapses and/or development of new MRI lesions but increased risk for disease worsening, with physical and cognitive decline. Systematic analysis–gathered data from clinical trials suggest an inadequate benefit of available DMTs in patients over 50 years, although the data have limitations, as most studies in relapsing MS did not enroll patients over the age of 55 years. In progressive MS trials, the median age of participants is 47 years; therefore, available data on aging populations are currently limited and cannot fully justify whether the medication is actually beneficial.
Another challenge in treating aging pwMS besides the limited benefit of DMTs is concern regarding safety and tolerability, especially as the most potent medications, which are now considered the most efficacious interventions for MS, are immunosuppressive agents. Aging populations with known weaker immune systems (immunosenescence) that are exposed to immunosuppressive interventions can be more susceptible to infections, have a decreased response to vaccinations, and face an increased risk of cancer.
The aging population is also known to have other health issues (comorbidities) and, therefore, may become more vulnerable to side effects from DMTs, making it necessary to consider a different management approach. Until more effective and safe therapeutic interventions become available for aging pwMS, discontinuation or de-escalation are the most frequently used approaches. Choosing between continuing, discontinuing, or de-escalating DMTs when treating aging MS patients is a complex process that requires careful consideration as well as active patient and patient family engagement in the final management decision.
The 2022 DISCO-MS trial was the first randomized discontinuation trial of MS drugs in older pwMS. The trial was designed to investigate the effect of discontinuing DMTs in patients aged 55 years and older who had not had recent relapses for at least 5 years and had no recent or new MRI lesions for at least 3 years. This multicenter study was conducted by the University of Colorado (supported/funded by a Patient-Centered Outcomes Research Institute grant) and included 259 participants with a median age of 63 years. Participants were randomly assigned to either continue or discontinue treatment and were followed for up to 22 months. The results of the DISCO-MS trial showed that 1 of 128 participants who stayed on medication had a relapse, and 3 of 131 people who discontinued medication had a relapse. There were no significant differences between the groups in progression of disability, cognition, quality of life, or adverse events. However, more participants who discontinued DMTs had new MRI lesions (16 vs 6), although there was no relationship to relapses or disability progression. Based on a noninferiority study design, the primary outcome (combined relapses and/or new MRI lesions) was not reached in this study. Other retrospective studies, such as a large study conducted in 2018, showed that most patients over age 60 years who discontinued DMTs remained off DMTs. These studies provide preliminary data that may guide clinicians who are considering discontinuing DMTs in their aging patients.
The second approach is de-escalation, which aims primarily to minimize the risk of side effects and complications while maintaining efficacy. Therefore, de-escalating MS medication in aging pwMS should always be done with great care. Some factors that should be considered when de-escalating treatment include the patient's age, their overall health, and the severity of their MS symptoms. Some approaches to de-escalating MS medication include gradually reducing the dosage of the medication over time or increasing the interval between the administration of infusible medications. This can help minimize the risk of side effects and complications, while still monitoring for maintained efficacy. These changes require shared decision-making between practitioners and patients after discussing the potential risks of MS relapse, new MRI lesions, or disease progression, along with the potential benefits of reducing medication-related side effects. Another approach is to switch to a different type of medication that is less immunosuppressive (ie, immunomodulatory) and that may be better suited to the patient's needs; these medications are less likely to cause side effects in older patients or may be better tolerated by patients with certain health conditions.
DMTs may cause side effects in patients of any age, but aging patients may be more susceptible to certain side effects due to changes in their physiology and increased vulnerability due to other health issues. Some side effects of DMTs in aging pwMS that should be considered include:
Cardiovascular issues: some DMTs may increase the risk of cardiovascular complications such as hypertension, hyperlipidemia, and heart failure, which may be more concerning in aging patients who may already have cardiovascular risk factors.
Infections: aging patients may be more vulnerable to more severe infections, which often require hospitalization. Such patients are also at higher risk for opportunistic infections, such as zoster infections, or progressive multifocal leukoencephalopathy due to changes in the weakening of their immune system function and higher prevalence of other health issues.
Skin reactions/change to skin pathology: sphingosine-1-phosphate receptor modulators are oral DMTs for MS that were associated with cases of basal cell carcinoma in clinical trials.
Ultimately, the decision to continue, discontinue, or de-escalate DMTs in aging pwMS should be based on the individual patient's needs and circumstances. It is important for clinicians to work closely with their patients to develop a personalized treatment plan that considers all the relevant benefits and risks. In the meantime, more research is needed on this topic to provide better outcomes for our growing population of aging patients who are living with MS.
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and neurodegenerative disease that affects the central nervous system. While there is no cure for MS, significant progress has been made during the last 2 decades, with over 25 medications developed, including disease modifying therapies (DMTs) that have shown benefit in reducing the number of acute events (relapses), curbing the development of new lesions seen on magnetic resonance imaging (MRI), and slowing disease progression/worsening. However, the benefit of available DMTs is seen primarily during the inflammatory stage of the disease (relapsing remitting) and is less clear in the later stages (secondary-progressive disease). Age was shown to be one of the most consistent contributing factors linked to disease worsening, and most studies suggest limited benefit of available DMTs in patients older than 50 years.
Meanwhile, the aging MS population is increasing worldwide, with most patients being between ages 55 and 65 years—a trend considered related to a general extended life expectancy, better diagnosis, early initiation of efficient DMTs, and improved general medical care. As persons with MS (pwMS) age, there is a clear change in the clinical presentation, with reduced risk for relapses and/or development of new MRI lesions but increased risk for disease worsening, with physical and cognitive decline. Systematic analysis–gathered data from clinical trials suggest an inadequate benefit of available DMTs in patients over 50 years, although the data have limitations, as most studies in relapsing MS did not enroll patients over the age of 55 years. In progressive MS trials, the median age of participants is 47 years; therefore, available data on aging populations are currently limited and cannot fully justify whether the medication is actually beneficial.
Another challenge in treating aging pwMS besides the limited benefit of DMTs is concern regarding safety and tolerability, especially as the most potent medications, which are now considered the most efficacious interventions for MS, are immunosuppressive agents. Aging populations with known weaker immune systems (immunosenescence) that are exposed to immunosuppressive interventions can be more susceptible to infections, have a decreased response to vaccinations, and face an increased risk of cancer.
The aging population is also known to have other health issues (comorbidities) and, therefore, may become more vulnerable to side effects from DMTs, making it necessary to consider a different management approach. Until more effective and safe therapeutic interventions become available for aging pwMS, discontinuation or de-escalation are the most frequently used approaches. Choosing between continuing, discontinuing, or de-escalating DMTs when treating aging MS patients is a complex process that requires careful consideration as well as active patient and patient family engagement in the final management decision.
The 2022 DISCO-MS trial was the first randomized discontinuation trial of MS drugs in older pwMS. The trial was designed to investigate the effect of discontinuing DMTs in patients aged 55 years and older who had not had recent relapses for at least 5 years and had no recent or new MRI lesions for at least 3 years. This multicenter study was conducted by the University of Colorado (supported/funded by a Patient-Centered Outcomes Research Institute grant) and included 259 participants with a median age of 63 years. Participants were randomly assigned to either continue or discontinue treatment and were followed for up to 22 months. The results of the DISCO-MS trial showed that 1 of 128 participants who stayed on medication had a relapse, and 3 of 131 people who discontinued medication had a relapse. There were no significant differences between the groups in progression of disability, cognition, quality of life, or adverse events. However, more participants who discontinued DMTs had new MRI lesions (16 vs 6), although there was no relationship to relapses or disability progression. Based on a noninferiority study design, the primary outcome (combined relapses and/or new MRI lesions) was not reached in this study. Other retrospective studies, such as a large study conducted in 2018, showed that most patients over age 60 years who discontinued DMTs remained off DMTs. These studies provide preliminary data that may guide clinicians who are considering discontinuing DMTs in their aging patients.
The second approach is de-escalation, which aims primarily to minimize the risk of side effects and complications while maintaining efficacy. Therefore, de-escalating MS medication in aging pwMS should always be done with great care. Some factors that should be considered when de-escalating treatment include the patient's age, their overall health, and the severity of their MS symptoms. Some approaches to de-escalating MS medication include gradually reducing the dosage of the medication over time or increasing the interval between the administration of infusible medications. This can help minimize the risk of side effects and complications, while still monitoring for maintained efficacy. These changes require shared decision-making between practitioners and patients after discussing the potential risks of MS relapse, new MRI lesions, or disease progression, along with the potential benefits of reducing medication-related side effects. Another approach is to switch to a different type of medication that is less immunosuppressive (ie, immunomodulatory) and that may be better suited to the patient's needs; these medications are less likely to cause side effects in older patients or may be better tolerated by patients with certain health conditions.
DMTs may cause side effects in patients of any age, but aging patients may be more susceptible to certain side effects due to changes in their physiology and increased vulnerability due to other health issues. Some side effects of DMTs in aging pwMS that should be considered include:
Cardiovascular issues: some DMTs may increase the risk of cardiovascular complications such as hypertension, hyperlipidemia, and heart failure, which may be more concerning in aging patients who may already have cardiovascular risk factors.
Infections: aging patients may be more vulnerable to more severe infections, which often require hospitalization. Such patients are also at higher risk for opportunistic infections, such as zoster infections, or progressive multifocal leukoencephalopathy due to changes in the weakening of their immune system function and higher prevalence of other health issues.
Skin reactions/change to skin pathology: sphingosine-1-phosphate receptor modulators are oral DMTs for MS that were associated with cases of basal cell carcinoma in clinical trials.
Ultimately, the decision to continue, discontinue, or de-escalate DMTs in aging pwMS should be based on the individual patient's needs and circumstances. It is important for clinicians to work closely with their patients to develop a personalized treatment plan that considers all the relevant benefits and risks. In the meantime, more research is needed on this topic to provide better outcomes for our growing population of aging patients who are living with MS.
Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and neurodegenerative disease that affects the central nervous system. While there is no cure for MS, significant progress has been made during the last 2 decades, with over 25 medications developed, including disease modifying therapies (DMTs) that have shown benefit in reducing the number of acute events (relapses), curbing the development of new lesions seen on magnetic resonance imaging (MRI), and slowing disease progression/worsening. However, the benefit of available DMTs is seen primarily during the inflammatory stage of the disease (relapsing remitting) and is less clear in the later stages (secondary-progressive disease). Age was shown to be one of the most consistent contributing factors linked to disease worsening, and most studies suggest limited benefit of available DMTs in patients older than 50 years.
Meanwhile, the aging MS population is increasing worldwide, with most patients being between ages 55 and 65 years—a trend considered related to a general extended life expectancy, better diagnosis, early initiation of efficient DMTs, and improved general medical care. As persons with MS (pwMS) age, there is a clear change in the clinical presentation, with reduced risk for relapses and/or development of new MRI lesions but increased risk for disease worsening, with physical and cognitive decline. Systematic analysis–gathered data from clinical trials suggest an inadequate benefit of available DMTs in patients over 50 years, although the data have limitations, as most studies in relapsing MS did not enroll patients over the age of 55 years. In progressive MS trials, the median age of participants is 47 years; therefore, available data on aging populations are currently limited and cannot fully justify whether the medication is actually beneficial.
Another challenge in treating aging pwMS besides the limited benefit of DMTs is concern regarding safety and tolerability, especially as the most potent medications, which are now considered the most efficacious interventions for MS, are immunosuppressive agents. Aging populations with known weaker immune systems (immunosenescence) that are exposed to immunosuppressive interventions can be more susceptible to infections, have a decreased response to vaccinations, and face an increased risk of cancer.
The aging population is also known to have other health issues (comorbidities) and, therefore, may become more vulnerable to side effects from DMTs, making it necessary to consider a different management approach. Until more effective and safe therapeutic interventions become available for aging pwMS, discontinuation or de-escalation are the most frequently used approaches. Choosing between continuing, discontinuing, or de-escalating DMTs when treating aging MS patients is a complex process that requires careful consideration as well as active patient and patient family engagement in the final management decision.
The 2022 DISCO-MS trial was the first randomized discontinuation trial of MS drugs in older pwMS. The trial was designed to investigate the effect of discontinuing DMTs in patients aged 55 years and older who had not had recent relapses for at least 5 years and had no recent or new MRI lesions for at least 3 years. This multicenter study was conducted by the University of Colorado (supported/funded by a Patient-Centered Outcomes Research Institute grant) and included 259 participants with a median age of 63 years. Participants were randomly assigned to either continue or discontinue treatment and were followed for up to 22 months. The results of the DISCO-MS trial showed that 1 of 128 participants who stayed on medication had a relapse, and 3 of 131 people who discontinued medication had a relapse. There were no significant differences between the groups in progression of disability, cognition, quality of life, or adverse events. However, more participants who discontinued DMTs had new MRI lesions (16 vs 6), although there was no relationship to relapses or disability progression. Based on a noninferiority study design, the primary outcome (combined relapses and/or new MRI lesions) was not reached in this study. Other retrospective studies, such as a large study conducted in 2018, showed that most patients over age 60 years who discontinued DMTs remained off DMTs. These studies provide preliminary data that may guide clinicians who are considering discontinuing DMTs in their aging patients.
The second approach is de-escalation, which aims primarily to minimize the risk of side effects and complications while maintaining efficacy. Therefore, de-escalating MS medication in aging pwMS should always be done with great care. Some factors that should be considered when de-escalating treatment include the patient's age, their overall health, and the severity of their MS symptoms. Some approaches to de-escalating MS medication include gradually reducing the dosage of the medication over time or increasing the interval between the administration of infusible medications. This can help minimize the risk of side effects and complications, while still monitoring for maintained efficacy. These changes require shared decision-making between practitioners and patients after discussing the potential risks of MS relapse, new MRI lesions, or disease progression, along with the potential benefits of reducing medication-related side effects. Another approach is to switch to a different type of medication that is less immunosuppressive (ie, immunomodulatory) and that may be better suited to the patient's needs; these medications are less likely to cause side effects in older patients or may be better tolerated by patients with certain health conditions.
DMTs may cause side effects in patients of any age, but aging patients may be more susceptible to certain side effects due to changes in their physiology and increased vulnerability due to other health issues. Some side effects of DMTs in aging pwMS that should be considered include:
Cardiovascular issues: some DMTs may increase the risk of cardiovascular complications such as hypertension, hyperlipidemia, and heart failure, which may be more concerning in aging patients who may already have cardiovascular risk factors.
Infections: aging patients may be more vulnerable to more severe infections, which often require hospitalization. Such patients are also at higher risk for opportunistic infections, such as zoster infections, or progressive multifocal leukoencephalopathy due to changes in the weakening of their immune system function and higher prevalence of other health issues.
Skin reactions/change to skin pathology: sphingosine-1-phosphate receptor modulators are oral DMTs for MS that were associated with cases of basal cell carcinoma in clinical trials.
Ultimately, the decision to continue, discontinue, or de-escalate DMTs in aging pwMS should be based on the individual patient's needs and circumstances. It is important for clinicians to work closely with their patients to develop a personalized treatment plan that considers all the relevant benefits and risks. In the meantime, more research is needed on this topic to provide better outcomes for our growing population of aging patients who are living with MS.
Mediterranean diet improves cognition in MS
due to a potential neuroprotective mechanism, according to findings of a study that was released early, ahead of presentation at the annual meting of the American Academy of Neurology.
“We were most surprised by the magnitude of the results,” said Ilana Katz Sand, MD, associate professor of neurology at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai in New York. “We hypothesized a significant association between Mediterranean diet and cognition in MS, but we did not anticipate the 20% absolute difference, particularly because we rigorously controlled the demographic and health-related factors, like socioeconomic status, body mass index, and exercise habits.”
The Mediterranean diet consists of predominately vegetables, fruits, legumes, fish, and healthy fats while minimizing the consumption of dairy products, meats, and saturated acids. Previous literature has drawn an association between diet and MS symptomology, notably with regard to the Mediterranean diet. These studies indicated a connection between thalamic volume in patients with early MS as well as objectively captured MS-related disability. In this study, researchers have continued their investigation by exploring how the Mediterranean diet affects cognition.
In this cross-sectional observational study, investigators evaluated 563 people with MS ranging in age from 18 to 65 years (n = 563; 71% women; aged 44.2 ± 11.3 years). To accomplish this task, researchers conducted a retrospective chart review capturing data from patients with MS who had undergone neurobehavioral screenings. Qualifying subjects completed the Mediterranean Diet Adherence Screener (MEDAS) to determine the extent to which they adhered to the Mediterranean diet. A 14-item questionnaire, MEDAS assess a person’s usual intake of healthful foods such as vegetables and olive oil, as well as minimization of unhealthy foods such as butter and red meat. They also completed an analogue of the CICMAS cognitive battery comprised of a composite of Symbol Digit Modalities Test, Hopkins Verbal Learning Test, Revised, and CANTAB Paired Associate Learning.
Researchers evaluated patient-reported outcomes adjusted based on demographics (i.e., age, sex, race, ethnicity, and socioeconomic status) and health-related factors. These elements included body mass index, exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking.
The study excluded patients who had another primary neurological condition in addition to MS (n = 24), serious psychiatric illness such as schizophrenia (n = 5) or clinical relapse within 6 weeks (n = 2), or missing data (n = 13).
Based on the diet scores, investigators stratified participants into four groups. Those with the scores ranging from 0 to 4 were classified into the lowest group, while scores of 9 or greater qualified participants for the high group.
Investigators observed a significant association between a higher Mediterranean diet score and condition in the population sampled. They found a mean z-score of –0.67 (0.95). In addition, a higher MEDAS proved an independent indicator of better cognition (B = 0.08 [95% confidence interval (CI), 0.05, 0.11], beta = 0.20, P < .001). In fact, a high MEDAS independently correlated to a 20% lower risk for cognitive impairment (odds ratio [OR] = .80 {95% CI, 0.73, 0.89}, P < .001). Ultimately, the study’s findings demonstrated MEDAS served as the strongest health-related indicator of z-score and cognitive impairment. Moreover, dietary modification based on effect suggested stronger associations between diet and cognition with progressive disease as opposed to relapsing disease, as noted by the relationship between the z-score and cognition.
“Further research is needed,” Dr. Katz Sand said. “But because the progressive phenotype reflects more prominent neurodegeneration, the greater observed effect size in those with progressive MS suggests a potential neuroprotective mechanism.”
This study was funded in part by an Irma T. Hirschl/Monique Weill-Caulier Research Award to Dr. Katz Sand. Dr. Katz Sand and coauthors also received funding from the National Multiple Sclerosis Society.
due to a potential neuroprotective mechanism, according to findings of a study that was released early, ahead of presentation at the annual meting of the American Academy of Neurology.
“We were most surprised by the magnitude of the results,” said Ilana Katz Sand, MD, associate professor of neurology at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai in New York. “We hypothesized a significant association between Mediterranean diet and cognition in MS, but we did not anticipate the 20% absolute difference, particularly because we rigorously controlled the demographic and health-related factors, like socioeconomic status, body mass index, and exercise habits.”
The Mediterranean diet consists of predominately vegetables, fruits, legumes, fish, and healthy fats while minimizing the consumption of dairy products, meats, and saturated acids. Previous literature has drawn an association between diet and MS symptomology, notably with regard to the Mediterranean diet. These studies indicated a connection between thalamic volume in patients with early MS as well as objectively captured MS-related disability. In this study, researchers have continued their investigation by exploring how the Mediterranean diet affects cognition.
In this cross-sectional observational study, investigators evaluated 563 people with MS ranging in age from 18 to 65 years (n = 563; 71% women; aged 44.2 ± 11.3 years). To accomplish this task, researchers conducted a retrospective chart review capturing data from patients with MS who had undergone neurobehavioral screenings. Qualifying subjects completed the Mediterranean Diet Adherence Screener (MEDAS) to determine the extent to which they adhered to the Mediterranean diet. A 14-item questionnaire, MEDAS assess a person’s usual intake of healthful foods such as vegetables and olive oil, as well as minimization of unhealthy foods such as butter and red meat. They also completed an analogue of the CICMAS cognitive battery comprised of a composite of Symbol Digit Modalities Test, Hopkins Verbal Learning Test, Revised, and CANTAB Paired Associate Learning.
Researchers evaluated patient-reported outcomes adjusted based on demographics (i.e., age, sex, race, ethnicity, and socioeconomic status) and health-related factors. These elements included body mass index, exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking.
The study excluded patients who had another primary neurological condition in addition to MS (n = 24), serious psychiatric illness such as schizophrenia (n = 5) or clinical relapse within 6 weeks (n = 2), or missing data (n = 13).
Based on the diet scores, investigators stratified participants into four groups. Those with the scores ranging from 0 to 4 were classified into the lowest group, while scores of 9 or greater qualified participants for the high group.
Investigators observed a significant association between a higher Mediterranean diet score and condition in the population sampled. They found a mean z-score of –0.67 (0.95). In addition, a higher MEDAS proved an independent indicator of better cognition (B = 0.08 [95% confidence interval (CI), 0.05, 0.11], beta = 0.20, P < .001). In fact, a high MEDAS independently correlated to a 20% lower risk for cognitive impairment (odds ratio [OR] = .80 {95% CI, 0.73, 0.89}, P < .001). Ultimately, the study’s findings demonstrated MEDAS served as the strongest health-related indicator of z-score and cognitive impairment. Moreover, dietary modification based on effect suggested stronger associations between diet and cognition with progressive disease as opposed to relapsing disease, as noted by the relationship between the z-score and cognition.
“Further research is needed,” Dr. Katz Sand said. “But because the progressive phenotype reflects more prominent neurodegeneration, the greater observed effect size in those with progressive MS suggests a potential neuroprotective mechanism.”
This study was funded in part by an Irma T. Hirschl/Monique Weill-Caulier Research Award to Dr. Katz Sand. Dr. Katz Sand and coauthors also received funding from the National Multiple Sclerosis Society.
due to a potential neuroprotective mechanism, according to findings of a study that was released early, ahead of presentation at the annual meting of the American Academy of Neurology.
“We were most surprised by the magnitude of the results,” said Ilana Katz Sand, MD, associate professor of neurology at the Corinne Goldsmith Dickinson Center for MS at Mount Sinai in New York. “We hypothesized a significant association between Mediterranean diet and cognition in MS, but we did not anticipate the 20% absolute difference, particularly because we rigorously controlled the demographic and health-related factors, like socioeconomic status, body mass index, and exercise habits.”
The Mediterranean diet consists of predominately vegetables, fruits, legumes, fish, and healthy fats while minimizing the consumption of dairy products, meats, and saturated acids. Previous literature has drawn an association between diet and MS symptomology, notably with regard to the Mediterranean diet. These studies indicated a connection between thalamic volume in patients with early MS as well as objectively captured MS-related disability. In this study, researchers have continued their investigation by exploring how the Mediterranean diet affects cognition.
In this cross-sectional observational study, investigators evaluated 563 people with MS ranging in age from 18 to 65 years (n = 563; 71% women; aged 44.2 ± 11.3 years). To accomplish this task, researchers conducted a retrospective chart review capturing data from patients with MS who had undergone neurobehavioral screenings. Qualifying subjects completed the Mediterranean Diet Adherence Screener (MEDAS) to determine the extent to which they adhered to the Mediterranean diet. A 14-item questionnaire, MEDAS assess a person’s usual intake of healthful foods such as vegetables and olive oil, as well as minimization of unhealthy foods such as butter and red meat. They also completed an analogue of the CICMAS cognitive battery comprised of a composite of Symbol Digit Modalities Test, Hopkins Verbal Learning Test, Revised, and CANTAB Paired Associate Learning.
Researchers evaluated patient-reported outcomes adjusted based on demographics (i.e., age, sex, race, ethnicity, and socioeconomic status) and health-related factors. These elements included body mass index, exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking.
The study excluded patients who had another primary neurological condition in addition to MS (n = 24), serious psychiatric illness such as schizophrenia (n = 5) or clinical relapse within 6 weeks (n = 2), or missing data (n = 13).
Based on the diet scores, investigators stratified participants into four groups. Those with the scores ranging from 0 to 4 were classified into the lowest group, while scores of 9 or greater qualified participants for the high group.
Investigators observed a significant association between a higher Mediterranean diet score and condition in the population sampled. They found a mean z-score of –0.67 (0.95). In addition, a higher MEDAS proved an independent indicator of better cognition (B = 0.08 [95% confidence interval (CI), 0.05, 0.11], beta = 0.20, P < .001). In fact, a high MEDAS independently correlated to a 20% lower risk for cognitive impairment (odds ratio [OR] = .80 {95% CI, 0.73, 0.89}, P < .001). Ultimately, the study’s findings demonstrated MEDAS served as the strongest health-related indicator of z-score and cognitive impairment. Moreover, dietary modification based on effect suggested stronger associations between diet and cognition with progressive disease as opposed to relapsing disease, as noted by the relationship between the z-score and cognition.
“Further research is needed,” Dr. Katz Sand said. “But because the progressive phenotype reflects more prominent neurodegeneration, the greater observed effect size in those with progressive MS suggests a potential neuroprotective mechanism.”
This study was funded in part by an Irma T. Hirschl/Monique Weill-Caulier Research Award to Dr. Katz Sand. Dr. Katz Sand and coauthors also received funding from the National Multiple Sclerosis Society.
FROM AAN 2023
