ACTRIMS 2019

DALLAS – Rhonda Voskuhl, MD, delivered the Kenneth P. Johnson Memorial lecture at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. In an hour-long talk, Dr. Voskuhl outlined her research approach, which she terms the “bedside to bench to bedside” strategy.
 

“My view has been that, when we start out research based on a molecule, we don’t really know for sure its clinical relevance. It’s kind of high risk, because you could go through a lot of work, for many years,” she said in a video interview. When work begins in vitro, the researcher runs the risk of proceeding from test tubes, to animal experiments, and then to people, “and then ultimately finding out that it’s not relevant,” said Dr. Voskuhl, director of the multiple sclerosis (MS) program and Jack H. Skirball Chair of Multiple Sclerosis Research at the University of California, Los Angeles.

“And so I just thought, to derisk this whole thing, I think I want to start at the end and then work backwards,” by choosing a physiologically relevant manifestation of MS, she said. “We know that there’s something there. ... All we have to do is figure it out.”

In iterative fashion, Dr. Voskuhl proceeds from the clinical observation, “which we know is true, and then go to the laboratory bench and figure it out by doing a lot of manipulation and isolation of one thing versus another.”

This process allows researchers to narrow down fruitful pathways before returning to the patient to conduct clinical trials using the one or two promising avenues discovered with bench science and animal models, she said.

“When you put this in the context of cell-specific and region-specific gene expression, to find disability-specific treatments,” Dr. Voskuhl said, this targeted approach helps address the fact that MS patients differ so much in their presentations and disease course.

“We know that, for example, the neuronal cells differ, and some of the neurotrophic cells differ from pathway to pathway; furthermore, what’s important is that oligocytes and astrocytes and dendrocytes have been shown to differ from one region of the brain and spinal cord to another. So these clearly would have different gene expression signatures, potentially posing different targets for treatment,” Dr. Voskuhl said.

[email protected]

DALLAS – Rhonda Voskuhl, MD, delivered the Kenneth P. Johnson Memorial lecture at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. In an hour-long talk, Dr. Voskuhl outlined her research approach, which she terms the “bedside to bench to bedside” strategy.
 

“My view has been that, when we start out research based on a molecule, we don’t really know for sure its clinical relevance. It’s kind of high risk, because you could go through a lot of work, for many years,” she said in a video interview. When work begins in vitro, the researcher runs the risk of proceeding from test tubes, to animal experiments, and then to people, “and then ultimately finding out that it’s not relevant,” said Dr. Voskuhl, director of the multiple sclerosis (MS) program and Jack H. Skirball Chair of Multiple Sclerosis Research at the University of California, Los Angeles.

“And so I just thought, to derisk this whole thing, I think I want to start at the end and then work backwards,” by choosing a physiologically relevant manifestation of MS, she said. “We know that there’s something there. ... All we have to do is figure it out.”

In iterative fashion, Dr. Voskuhl proceeds from the clinical observation, “which we know is true, and then go to the laboratory bench and figure it out by doing a lot of manipulation and isolation of one thing versus another.”

This process allows researchers to narrow down fruitful pathways before returning to the patient to conduct clinical trials using the one or two promising avenues discovered with bench science and animal models, she said.

“When you put this in the context of cell-specific and region-specific gene expression, to find disability-specific treatments,” Dr. Voskuhl said, this targeted approach helps address the fact that MS patients differ so much in their presentations and disease course.

“We know that, for example, the neuronal cells differ, and some of the neurotrophic cells differ from pathway to pathway; furthermore, what’s important is that oligocytes and astrocytes and dendrocytes have been shown to differ from one region of the brain and spinal cord to another. So these clearly would have different gene expression signatures, potentially posing different targets for treatment,” Dr. Voskuhl said.

[email protected]

DALLAS – Rhonda Voskuhl, MD, delivered the Kenneth P. Johnson Memorial lecture at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. In an hour-long talk, Dr. Voskuhl outlined her research approach, which she terms the “bedside to bench to bedside” strategy.
 

“My view has been that, when we start out research based on a molecule, we don’t really know for sure its clinical relevance. It’s kind of high risk, because you could go through a lot of work, for many years,” she said in a video interview. When work begins in vitro, the researcher runs the risk of proceeding from test tubes, to animal experiments, and then to people, “and then ultimately finding out that it’s not relevant,” said Dr. Voskuhl, director of the multiple sclerosis (MS) program and Jack H. Skirball Chair of Multiple Sclerosis Research at the University of California, Los Angeles.

“And so I just thought, to derisk this whole thing, I think I want to start at the end and then work backwards,” by choosing a physiologically relevant manifestation of MS, she said. “We know that there’s something there. ... All we have to do is figure it out.”

In iterative fashion, Dr. Voskuhl proceeds from the clinical observation, “which we know is true, and then go to the laboratory bench and figure it out by doing a lot of manipulation and isolation of one thing versus another.”

This process allows researchers to narrow down fruitful pathways before returning to the patient to conduct clinical trials using the one or two promising avenues discovered with bench science and animal models, she said.

“When you put this in the context of cell-specific and region-specific gene expression, to find disability-specific treatments,” Dr. Voskuhl said, this targeted approach helps address the fact that MS patients differ so much in their presentations and disease course.

“We know that, for example, the neuronal cells differ, and some of the neurotrophic cells differ from pathway to pathway; furthermore, what’s important is that oligocytes and astrocytes and dendrocytes have been shown to differ from one region of the brain and spinal cord to another. So these clearly would have different gene expression signatures, potentially posing different targets for treatment,” Dr. Voskuhl said.

[email protected]

DALLAS – The time is right to bring big data and high-horsepower computation to the thorniest problems in multiple sclerosis (MS) research, said Jennifer Graves, MD, who cochaired the closing session at the meeting held by the Americas Committee for Research and Treatment in Multiple Sclerosis. The session focused on harnessing machine learning, deep learning, and the newest noninvasive observational techniques to move research and clinical care forward.

“We’ve reached a point in MS research where we’re hitting some stumbling blocks. And a lot of those stumbling blocks are related to how well and how precisely we can measure phenotype in MS. The reason that’s important is that our next frontier is treating progressive MS – and what that requires is finding things that let us know what’s happening at the biological level, so that we can screen drugs faster. We can’t afford to have 3- to 5-year clinical trials. ... Because our patients can’t wait,” said Dr. Graves, an associate professor of neuroscience at the University of California, San Diego.

“We can use all sorts of big data sources, whether it’s the rich imaging data we get on patients when they go into the MRI scanner, whether it’s wearable sensors,” or even newer technology, Dr. Graves said. “We can use technology to give us the sensitivity that we’ve been missing.”

Wearable technology, including accelerometers, can track physical activity that tracks with outcomes in MS, she added. As the tech armament increases, so will data available for analysis and correlation.

However, the key to progress will be to focus on technology that measures change over time. “This is the key: sensitivity to change over time. A lot of things can be associated with disability,” said Dr. Graves, but the key is tracking what changes in an individual patient with disease progression, “so that we can detect treatment effects or side effects.”

[email protected]

DALLAS – The time is right to bring big data and high-horsepower computation to the thorniest problems in multiple sclerosis (MS) research, said Jennifer Graves, MD, who cochaired the closing session at the meeting held by the Americas Committee for Research and Treatment in Multiple Sclerosis. The session focused on harnessing machine learning, deep learning, and the newest noninvasive observational techniques to move research and clinical care forward.

“We’ve reached a point in MS research where we’re hitting some stumbling blocks. And a lot of those stumbling blocks are related to how well and how precisely we can measure phenotype in MS. The reason that’s important is that our next frontier is treating progressive MS – and what that requires is finding things that let us know what’s happening at the biological level, so that we can screen drugs faster. We can’t afford to have 3- to 5-year clinical trials. ... Because our patients can’t wait,” said Dr. Graves, an associate professor of neuroscience at the University of California, San Diego.

“We can use all sorts of big data sources, whether it’s the rich imaging data we get on patients when they go into the MRI scanner, whether it’s wearable sensors,” or even newer technology, Dr. Graves said. “We can use technology to give us the sensitivity that we’ve been missing.”

Wearable technology, including accelerometers, can track physical activity that tracks with outcomes in MS, she added. As the tech armament increases, so will data available for analysis and correlation.

However, the key to progress will be to focus on technology that measures change over time. “This is the key: sensitivity to change over time. A lot of things can be associated with disability,” said Dr. Graves, but the key is tracking what changes in an individual patient with disease progression, “so that we can detect treatment effects or side effects.”

[email protected]

DALLAS – The time is right to bring big data and high-horsepower computation to the thorniest problems in multiple sclerosis (MS) research, said Jennifer Graves, MD, who cochaired the closing session at the meeting held by the Americas Committee for Research and Treatment in Multiple Sclerosis. The session focused on harnessing machine learning, deep learning, and the newest noninvasive observational techniques to move research and clinical care forward.

“We’ve reached a point in MS research where we’re hitting some stumbling blocks. And a lot of those stumbling blocks are related to how well and how precisely we can measure phenotype in MS. The reason that’s important is that our next frontier is treating progressive MS – and what that requires is finding things that let us know what’s happening at the biological level, so that we can screen drugs faster. We can’t afford to have 3- to 5-year clinical trials. ... Because our patients can’t wait,” said Dr. Graves, an associate professor of neuroscience at the University of California, San Diego.

“We can use all sorts of big data sources, whether it’s the rich imaging data we get on patients when they go into the MRI scanner, whether it’s wearable sensors,” or even newer technology, Dr. Graves said. “We can use technology to give us the sensitivity that we’ve been missing.”

Wearable technology, including accelerometers, can track physical activity that tracks with outcomes in MS, she added. As the tech armament increases, so will data available for analysis and correlation.

However, the key to progress will be to focus on technology that measures change over time. “This is the key: sensitivity to change over time. A lot of things can be associated with disability,” said Dr. Graves, but the key is tracking what changes in an individual patient with disease progression, “so that we can detect treatment effects or side effects.”

[email protected]

DALLAS – In a cohort of patients with multiple sclerosis, a history of migraine was associated with more severe disability and significantly slower walking speeds, researchers reported at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“Traditional migraine risk factors such as obesity, anxiety, and depression were also overrepresented in our cohort” of patients with multiple sclerosis (MS) and migraine, said Anne M. Damian, MD, of Johns Hopkins University, Baltimore, and her research colleagues.

Migraine is common in patients with MS, but whether migraine plays a role in MS disease course or MS symptom severity is unknown. Dr. Damian and her colleagues conducted an observational study to examine the associations between migraine history, disability, and neurologic function in patients with MS and whether migraine tends to occur with other comorbid conditions in MS.

They analyzed data from 289 patients (79% female; mean age, 49.2 years) patients with MS who completed the Multiple Sclerosis Performance Test (MSPT), an iPad version of the MS Functional Composite. MS outcome measures included disability (such as the Patient Determined Disease Steps) and objective neurologic outcomes (such as walking speed, manual dexterity, and processing speed). Patients also completed a questionnaire about comorbidities, including history of physician-diagnosed migraine, diabetes, hypertension, hypercholesterolemia, heart disease, sleep apnea, depression, and anxiety.

The researchers used generalized linear models adjusted for age, sex, MS subtype, MS duration, years of education, and body mass index to evaluate the association between history of migraine and MS outcomes.

Compared with patients with MS without migraine, migraineurs (n = 65) tended to be younger (mean age, 44.3 years vs. 50.4 years) and were more likely to be overweight or obese (73.9% vs. 51.6%). In addition, patients with MS and migraine were more likely to have a history of depression (46.2% vs. 24.2%), anxiety (30.8% vs. 18.8%), and severe rather than mild disability (odds ratio, 3.08; 95% confidence, 1.04-9.20). Migraine also was associated with significantly slower walking speeds (9.08% slower; 95% CI, 0.82%-18.77%). Migraine was not associated with processing speed or manual dexterity, however.

If an association between migraine history and worse MS disability is confirmed, migraine history may be a factor that neurologists could consider when making MS treatment decisions, Dr. Damian said. The researchers noted that migraine was reported by patients and not detected using a validated questionnaire. Future studies should investigate whether MS lesions on MRI differ in migraineurs and whether migraine predicts future neurologic disability in patients with MS.

Collection of the MSPT outcomes was sponsored by Biogen.

[email protected]

SOURCE: Damian AM et al. ACTRIMS Forum 2019, Abstract 78.

DALLAS – In a cohort of patients with multiple sclerosis, a history of migraine was associated with more severe disability and significantly slower walking speeds, researchers reported at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“Traditional migraine risk factors such as obesity, anxiety, and depression were also overrepresented in our cohort” of patients with multiple sclerosis (MS) and migraine, said Anne M. Damian, MD, of Johns Hopkins University, Baltimore, and her research colleagues.

Migraine is common in patients with MS, but whether migraine plays a role in MS disease course or MS symptom severity is unknown. Dr. Damian and her colleagues conducted an observational study to examine the associations between migraine history, disability, and neurologic function in patients with MS and whether migraine tends to occur with other comorbid conditions in MS.

They analyzed data from 289 patients (79% female; mean age, 49.2 years) patients with MS who completed the Multiple Sclerosis Performance Test (MSPT), an iPad version of the MS Functional Composite. MS outcome measures included disability (such as the Patient Determined Disease Steps) and objective neurologic outcomes (such as walking speed, manual dexterity, and processing speed). Patients also completed a questionnaire about comorbidities, including history of physician-diagnosed migraine, diabetes, hypertension, hypercholesterolemia, heart disease, sleep apnea, depression, and anxiety.

The researchers used generalized linear models adjusted for age, sex, MS subtype, MS duration, years of education, and body mass index to evaluate the association between history of migraine and MS outcomes.

Compared with patients with MS without migraine, migraineurs (n = 65) tended to be younger (mean age, 44.3 years vs. 50.4 years) and were more likely to be overweight or obese (73.9% vs. 51.6%). In addition, patients with MS and migraine were more likely to have a history of depression (46.2% vs. 24.2%), anxiety (30.8% vs. 18.8%), and severe rather than mild disability (odds ratio, 3.08; 95% confidence, 1.04-9.20). Migraine also was associated with significantly slower walking speeds (9.08% slower; 95% CI, 0.82%-18.77%). Migraine was not associated with processing speed or manual dexterity, however.

If an association between migraine history and worse MS disability is confirmed, migraine history may be a factor that neurologists could consider when making MS treatment decisions, Dr. Damian said. The researchers noted that migraine was reported by patients and not detected using a validated questionnaire. Future studies should investigate whether MS lesions on MRI differ in migraineurs and whether migraine predicts future neurologic disability in patients with MS.

Collection of the MSPT outcomes was sponsored by Biogen.

[email protected]

SOURCE: Damian AM et al. ACTRIMS Forum 2019, Abstract 78.

DALLAS – In a cohort of patients with multiple sclerosis, a history of migraine was associated with more severe disability and significantly slower walking speeds, researchers reported at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“Traditional migraine risk factors such as obesity, anxiety, and depression were also overrepresented in our cohort” of patients with multiple sclerosis (MS) and migraine, said Anne M. Damian, MD, of Johns Hopkins University, Baltimore, and her research colleagues.

Migraine is common in patients with MS, but whether migraine plays a role in MS disease course or MS symptom severity is unknown. Dr. Damian and her colleagues conducted an observational study to examine the associations between migraine history, disability, and neurologic function in patients with MS and whether migraine tends to occur with other comorbid conditions in MS.

They analyzed data from 289 patients (79% female; mean age, 49.2 years) patients with MS who completed the Multiple Sclerosis Performance Test (MSPT), an iPad version of the MS Functional Composite. MS outcome measures included disability (such as the Patient Determined Disease Steps) and objective neurologic outcomes (such as walking speed, manual dexterity, and processing speed). Patients also completed a questionnaire about comorbidities, including history of physician-diagnosed migraine, diabetes, hypertension, hypercholesterolemia, heart disease, sleep apnea, depression, and anxiety.

The researchers used generalized linear models adjusted for age, sex, MS subtype, MS duration, years of education, and body mass index to evaluate the association between history of migraine and MS outcomes.

Compared with patients with MS without migraine, migraineurs (n = 65) tended to be younger (mean age, 44.3 years vs. 50.4 years) and were more likely to be overweight or obese (73.9% vs. 51.6%). In addition, patients with MS and migraine were more likely to have a history of depression (46.2% vs. 24.2%), anxiety (30.8% vs. 18.8%), and severe rather than mild disability (odds ratio, 3.08; 95% confidence, 1.04-9.20). Migraine also was associated with significantly slower walking speeds (9.08% slower; 95% CI, 0.82%-18.77%). Migraine was not associated with processing speed or manual dexterity, however.

If an association between migraine history and worse MS disability is confirmed, migraine history may be a factor that neurologists could consider when making MS treatment decisions, Dr. Damian said. The researchers noted that migraine was reported by patients and not detected using a validated questionnaire. Future studies should investigate whether MS lesions on MRI differ in migraineurs and whether migraine predicts future neurologic disability in patients with MS.

Collection of the MSPT outcomes was sponsored by Biogen.

[email protected]

SOURCE: Damian AM et al. ACTRIMS Forum 2019, Abstract 78.

DALLAS – “Stem cell therapy is something that has been a topic of interest for neurologists for a while,” said Wijdan Rai, MD, speaking at the meeting presented by the American Committee for Treatment and Research in Multiple Sclerosis.

However, “stem cell tourism is notoriously difficult to study, because it’s not regulated; there’s no database we can access to try to figure out what exactly is going on in these clinics,” said Dr. Rai.

Dr. Rai, a neurology resident at the Ohio State University, Columbus, said that she and her colleagues had noticed patients with multiple sclerosis (MS) were asking more frequently about stem cell therapies, and mesenchymal stem cell therapy in particular.

To translate these anecdotal observations into more concrete data, Dr. Rai and her colleagues surveyed academic neurologists in the outpatient setting to see if their patients were asking them about medical tourism for stem cell therapy. Additionally, they were asked about patients who actually had sought out the therapy and if there were adverse reactions from stem cell therapy.

The 25-item questionnaire was sent to academic neurologists via an online survey tool called Synapse through the American Academy of Neurology. Dr. Rai and her colleagues found that over 90% of respondents had been asked about stem cell therapies and that 25% of respondents said their patients had some kind of complication from the treatment.

“Most commonly, it was some variation of an infection, like meningitis, encephalitis, or hepatitis C,” said Dr. Rai. Other physicians reported that their patients had spinal cord tumors, deterioration of MS, or stroke.

Dr. Rai said the survey data show that stem cell tourism is common and that patients can experience adverse events; with this evidence in hand, she hopes that a fact sheet can be developed and hosted on a website so physicians can point their patients to evidence-based information about stem cell therapies in MS.

[email protected]

DALLAS – “Stem cell therapy is something that has been a topic of interest for neurologists for a while,” said Wijdan Rai, MD, speaking at the meeting presented by the American Committee for Treatment and Research in Multiple Sclerosis.

However, “stem cell tourism is notoriously difficult to study, because it’s not regulated; there’s no database we can access to try to figure out what exactly is going on in these clinics,” said Dr. Rai.

Dr. Rai, a neurology resident at the Ohio State University, Columbus, said that she and her colleagues had noticed patients with multiple sclerosis (MS) were asking more frequently about stem cell therapies, and mesenchymal stem cell therapy in particular.

To translate these anecdotal observations into more concrete data, Dr. Rai and her colleagues surveyed academic neurologists in the outpatient setting to see if their patients were asking them about medical tourism for stem cell therapy. Additionally, they were asked about patients who actually had sought out the therapy and if there were adverse reactions from stem cell therapy.

The 25-item questionnaire was sent to academic neurologists via an online survey tool called Synapse through the American Academy of Neurology. Dr. Rai and her colleagues found that over 90% of respondents had been asked about stem cell therapies and that 25% of respondents said their patients had some kind of complication from the treatment.

“Most commonly, it was some variation of an infection, like meningitis, encephalitis, or hepatitis C,” said Dr. Rai. Other physicians reported that their patients had spinal cord tumors, deterioration of MS, or stroke.

Dr. Rai said the survey data show that stem cell tourism is common and that patients can experience adverse events; with this evidence in hand, she hopes that a fact sheet can be developed and hosted on a website so physicians can point their patients to evidence-based information about stem cell therapies in MS.

[email protected]

DALLAS – “Stem cell therapy is something that has been a topic of interest for neurologists for a while,” said Wijdan Rai, MD, speaking at the meeting presented by the American Committee for Treatment and Research in Multiple Sclerosis.

However, “stem cell tourism is notoriously difficult to study, because it’s not regulated; there’s no database we can access to try to figure out what exactly is going on in these clinics,” said Dr. Rai.

Dr. Rai, a neurology resident at the Ohio State University, Columbus, said that she and her colleagues had noticed patients with multiple sclerosis (MS) were asking more frequently about stem cell therapies, and mesenchymal stem cell therapy in particular.

To translate these anecdotal observations into more concrete data, Dr. Rai and her colleagues surveyed academic neurologists in the outpatient setting to see if their patients were asking them about medical tourism for stem cell therapy. Additionally, they were asked about patients who actually had sought out the therapy and if there were adverse reactions from stem cell therapy.

The 25-item questionnaire was sent to academic neurologists via an online survey tool called Synapse through the American Academy of Neurology. Dr. Rai and her colleagues found that over 90% of respondents had been asked about stem cell therapies and that 25% of respondents said their patients had some kind of complication from the treatment.

“Most commonly, it was some variation of an infection, like meningitis, encephalitis, or hepatitis C,” said Dr. Rai. Other physicians reported that their patients had spinal cord tumors, deterioration of MS, or stroke.

Dr. Rai said the survey data show that stem cell tourism is common and that patients can experience adverse events; with this evidence in hand, she hopes that a fact sheet can be developed and hosted on a website so physicians can point their patients to evidence-based information about stem cell therapies in MS.

[email protected]

DALLAS – A smartphone can be a valuable extension of clinician assessment in multiple sclerosis and other neurologic disorders, affording the opportunity for patients to complete some assessments at home.

Alexandra Boukhvalova, a medical student at the University of Maryland School of Medicine, Baltimore, and her collaborators developed an interactive smartphone app to assess some aspects of cognitive and motor function for patients with multiple sclerosis (MS). Their findings were reported during a poster session at the meeting held by the American Society for Prevention and Treatment in Multiple Sclerosis.

“The clinician assessment is an hour-long assessment; it requires a trained neurologist,” Ms. Boukhvalova pointed out. In thinking about how app-based assessment could augment the clinical exam, she and her collaborators realized that “a lot of the neurologic exam is still quite subjective – so is there a way that we can make that exam more objective and quantifiable and also add a little bit of ease with accessibility and mobility?

“We created a suite of test apps ... to assess different neurological systems, ranging from motor function, cognitive and visual dysfunction, general fatigue, and strength,” she said. The apps included tapping tests and balloon-popping tasks, along with measures to give some indication of spasticity by assessing the smoothness of movements.

Participants completed the testing both in the clinic and from home. “We did not need an investigator present for patients to be able to complete the tests,” said Ms. Boukhvalova.

Ms. Boukhvalova and her colleagues compared performance on the gamified tasks between patients with MS and healthy controls. For all tasks, the participants with MS could clearly be differentiated from the healthy participants.

A further plus was that “The patients almost viewed these tests as games.” They reported that they enjoyed completing them, said Ms. Boukhvalova, adding that app-based assessments also offer an additional point of connection between MS patients and specialists, whom they may only see annually or semiannually.

Further app development may focus on utilizing sensor and accelerometer functions in smartphones to perform more natural and sophisticated motor analysis to look at gait and gross motor functioning, she said.

[email protected]

DALLAS – A smartphone can be a valuable extension of clinician assessment in multiple sclerosis and other neurologic disorders, affording the opportunity for patients to complete some assessments at home.

Alexandra Boukhvalova, a medical student at the University of Maryland School of Medicine, Baltimore, and her collaborators developed an interactive smartphone app to assess some aspects of cognitive and motor function for patients with multiple sclerosis (MS). Their findings were reported during a poster session at the meeting held by the American Society for Prevention and Treatment in Multiple Sclerosis.

“The clinician assessment is an hour-long assessment; it requires a trained neurologist,” Ms. Boukhvalova pointed out. In thinking about how app-based assessment could augment the clinical exam, she and her collaborators realized that “a lot of the neurologic exam is still quite subjective – so is there a way that we can make that exam more objective and quantifiable and also add a little bit of ease with accessibility and mobility?

“We created a suite of test apps ... to assess different neurological systems, ranging from motor function, cognitive and visual dysfunction, general fatigue, and strength,” she said. The apps included tapping tests and balloon-popping tasks, along with measures to give some indication of spasticity by assessing the smoothness of movements.

Participants completed the testing both in the clinic and from home. “We did not need an investigator present for patients to be able to complete the tests,” said Ms. Boukhvalova.

Ms. Boukhvalova and her colleagues compared performance on the gamified tasks between patients with MS and healthy controls. For all tasks, the participants with MS could clearly be differentiated from the healthy participants.

A further plus was that “The patients almost viewed these tests as games.” They reported that they enjoyed completing them, said Ms. Boukhvalova, adding that app-based assessments also offer an additional point of connection between MS patients and specialists, whom they may only see annually or semiannually.

Further app development may focus on utilizing sensor and accelerometer functions in smartphones to perform more natural and sophisticated motor analysis to look at gait and gross motor functioning, she said.

[email protected]

DALLAS – A smartphone can be a valuable extension of clinician assessment in multiple sclerosis and other neurologic disorders, affording the opportunity for patients to complete some assessments at home.

Alexandra Boukhvalova, a medical student at the University of Maryland School of Medicine, Baltimore, and her collaborators developed an interactive smartphone app to assess some aspects of cognitive and motor function for patients with multiple sclerosis (MS). Their findings were reported during a poster session at the meeting held by the American Society for Prevention and Treatment in Multiple Sclerosis.

“The clinician assessment is an hour-long assessment; it requires a trained neurologist,” Ms. Boukhvalova pointed out. In thinking about how app-based assessment could augment the clinical exam, she and her collaborators realized that “a lot of the neurologic exam is still quite subjective – so is there a way that we can make that exam more objective and quantifiable and also add a little bit of ease with accessibility and mobility?

“We created a suite of test apps ... to assess different neurological systems, ranging from motor function, cognitive and visual dysfunction, general fatigue, and strength,” she said. The apps included tapping tests and balloon-popping tasks, along with measures to give some indication of spasticity by assessing the smoothness of movements.

Participants completed the testing both in the clinic and from home. “We did not need an investigator present for patients to be able to complete the tests,” said Ms. Boukhvalova.

Ms. Boukhvalova and her colleagues compared performance on the gamified tasks between patients with MS and healthy controls. For all tasks, the participants with MS could clearly be differentiated from the healthy participants.

A further plus was that “The patients almost viewed these tests as games.” They reported that they enjoyed completing them, said Ms. Boukhvalova, adding that app-based assessments also offer an additional point of connection between MS patients and specialists, whom they may only see annually or semiannually.

Further app development may focus on utilizing sensor and accelerometer functions in smartphones to perform more natural and sophisticated motor analysis to look at gait and gross motor functioning, she said.

[email protected]

DALLAS – Patients with multiple sclerosis (MS) have a nearly 100% higher incidence of new treated depression, compared with matched patients without MS, according to an analysis of data from patients in the United Kingdom.

After a diagnosis of MS, the incidence of new treated depression is 229 per 10,000 person-years. In comparison, the incidence of new treated depression among matched patients without MS is 121 per 10,000 person-years, Neil Minton, MD, drug safety head at Celgene, reported at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

MS causes changes in the CNS that are associated with depression, but “data on rates of incident depression after MS diagnosis ... are limited,” Dr. Minton and his research colleagues said. To examine rates of treated incident depression in patients with MS after an MS diagnosis, compared with rates in a matched population of patients without MS, the researchers analyzed data from the U.K. Clinical Practice Research Datalink.

Their analysis included patients with MS who received a diagnosis of MS between 2001 and 2016, had at least 1 year of history available before the MS diagnosis, and had no history of treated depression. The researchers matched these patients with as many as 10 patients without MS by age, sex, general practice, record history length, and no history of treated depression. Treated depression was defined as a diagnosis code for depression and a prescription for an antidepressant treatment within 90 days. They used Byar’s method to estimate incidence rates and incidence rate ratios, the Kaplan-Meier method to generate cumulative incidence curves, and a log-rank test to compare the curves.

In all, 5,456 patients with MS and 45,712 matched patients without MS were included in the study. Patients’ median age was 42 years; 65% were female. Compared with patients without MS, patients with MS were more likely to have a history of untreated depression (9.6% vs. 7.5%) and to have received an antidepressant treatment for any indication before cohort entry (28.0% vs. 15.5%). Diagnoses for other psychiatric conditions were similar between the groups.

Incidence rates of treated depression were higher among women with MS, compared with men with MS – 241 versus 202 per 10,000 person-years. Compared with patients without MS, however, men with MS had a higher relative risk of treated depression (2.40 vs. 1.73).

The incidence rate ratios were similar in sensitivity analyses that excluded patients with a history of any psychiatric disorder at cohort entry and that did not require treatment to confirm a depression diagnosis.

The study was funded by a grant from Celgene.

[email protected]

SOURCE: Minton N et al. ACTRIMS Forum 2019, Abstract 82.

DALLAS – Patients with multiple sclerosis (MS) have a nearly 100% higher incidence of new treated depression, compared with matched patients without MS, according to an analysis of data from patients in the United Kingdom.

After a diagnosis of MS, the incidence of new treated depression is 229 per 10,000 person-years. In comparison, the incidence of new treated depression among matched patients without MS is 121 per 10,000 person-years, Neil Minton, MD, drug safety head at Celgene, reported at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

MS causes changes in the CNS that are associated with depression, but “data on rates of incident depression after MS diagnosis ... are limited,” Dr. Minton and his research colleagues said. To examine rates of treated incident depression in patients with MS after an MS diagnosis, compared with rates in a matched population of patients without MS, the researchers analyzed data from the U.K. Clinical Practice Research Datalink.

Their analysis included patients with MS who received a diagnosis of MS between 2001 and 2016, had at least 1 year of history available before the MS diagnosis, and had no history of treated depression. The researchers matched these patients with as many as 10 patients without MS by age, sex, general practice, record history length, and no history of treated depression. Treated depression was defined as a diagnosis code for depression and a prescription for an antidepressant treatment within 90 days. They used Byar’s method to estimate incidence rates and incidence rate ratios, the Kaplan-Meier method to generate cumulative incidence curves, and a log-rank test to compare the curves.

In all, 5,456 patients with MS and 45,712 matched patients without MS were included in the study. Patients’ median age was 42 years; 65% were female. Compared with patients without MS, patients with MS were more likely to have a history of untreated depression (9.6% vs. 7.5%) and to have received an antidepressant treatment for any indication before cohort entry (28.0% vs. 15.5%). Diagnoses for other psychiatric conditions were similar between the groups.

Incidence rates of treated depression were higher among women with MS, compared with men with MS – 241 versus 202 per 10,000 person-years. Compared with patients without MS, however, men with MS had a higher relative risk of treated depression (2.40 vs. 1.73).

The incidence rate ratios were similar in sensitivity analyses that excluded patients with a history of any psychiatric disorder at cohort entry and that did not require treatment to confirm a depression diagnosis.

The study was funded by a grant from Celgene.

[email protected]

SOURCE: Minton N et al. ACTRIMS Forum 2019, Abstract 82.

DALLAS – Patients with multiple sclerosis (MS) have a nearly 100% higher incidence of new treated depression, compared with matched patients without MS, according to an analysis of data from patients in the United Kingdom.

After a diagnosis of MS, the incidence of new treated depression is 229 per 10,000 person-years. In comparison, the incidence of new treated depression among matched patients without MS is 121 per 10,000 person-years, Neil Minton, MD, drug safety head at Celgene, reported at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

MS causes changes in the CNS that are associated with depression, but “data on rates of incident depression after MS diagnosis ... are limited,” Dr. Minton and his research colleagues said. To examine rates of treated incident depression in patients with MS after an MS diagnosis, compared with rates in a matched population of patients without MS, the researchers analyzed data from the U.K. Clinical Practice Research Datalink.

Their analysis included patients with MS who received a diagnosis of MS between 2001 and 2016, had at least 1 year of history available before the MS diagnosis, and had no history of treated depression. The researchers matched these patients with as many as 10 patients without MS by age, sex, general practice, record history length, and no history of treated depression. Treated depression was defined as a diagnosis code for depression and a prescription for an antidepressant treatment within 90 days. They used Byar’s method to estimate incidence rates and incidence rate ratios, the Kaplan-Meier method to generate cumulative incidence curves, and a log-rank test to compare the curves.

In all, 5,456 patients with MS and 45,712 matched patients without MS were included in the study. Patients’ median age was 42 years; 65% were female. Compared with patients without MS, patients with MS were more likely to have a history of untreated depression (9.6% vs. 7.5%) and to have received an antidepressant treatment for any indication before cohort entry (28.0% vs. 15.5%). Diagnoses for other psychiatric conditions were similar between the groups.

Incidence rates of treated depression were higher among women with MS, compared with men with MS – 241 versus 202 per 10,000 person-years. Compared with patients without MS, however, men with MS had a higher relative risk of treated depression (2.40 vs. 1.73).

The incidence rate ratios were similar in sensitivity analyses that excluded patients with a history of any psychiatric disorder at cohort entry and that did not require treatment to confirm a depression diagnosis.

The study was funded by a grant from Celgene.

[email protected]

SOURCE: Minton N et al. ACTRIMS Forum 2019, Abstract 82.

DALLAS – Patients with relapsing emitting multiple sclerosis who discontinued treatment after a period of disease inactivity had a similar time to next event, compared with those who remained on treatment, results from a single-center study showed.

In addition, being over the age of 45 years was associated with a better disease course after treatment discontinuation.

“Being clinically and radiologically stable for more than 2 years can be a potential milestone to regard the discontinuation of DMT [disease-modifying therapy] as a reasonable option in a subset of patients, especially patients who are nondisabled,” lead study author Hajime Yano, MD, said in an interview at the Americas Committee for Treatment and Research in Multiple Sclerosis.

According to Dr. Yano, a research fellow at the Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center in Boston, relapsing remitting multiple sclerosis (RRMS) patients without relapse for long periods on treatment may consider discontinuing DMT, but there is limited information regarding the impact of discontinuation, especially in terms of MRI activity.

In an effort to investigate the impact of DMT discontinuation on clinical and radiologic outcomes in RRMS patients, he and his colleagues identified 70 patients from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB) study, which was initiated in 2000 and has enrolled more than 2,400 patients cared for at the Partners Multiple Sclerosis Center. Relapse date, symptoms, and Expanded Disability Status Scale (EDSS) were evaluated at 6-month intervals for each patient during the time of clinic visits by the treating neurologist. Additionally, brain MRIs were performed annually.

Next, the researchers matched the patients with 70 patients who remained on DMT identified by age, sex, treatment, treatment duration, disease duration, and EDSS. They used univariate and multivariable Cox proportional hazard models to test the differences between DMT discontinuation status with time to clinical relapse, MRI event, disability progression, and any inflammatory event (either clinical relapse or MRI event).

The mean age of patients was 45 years, 87% were female, their mean disease duration was about 13 years, and they had been receiving treatment for a mean of about 6 years. In adjusted analyses, the 70 pairs of patients who discontinued DMT and patients who continued DMT had similar outcomes in time to clinical relapse (hazard ratio, 0.93; P = .84), MRI event (HR, 1.01; P = .98), disability progression (HR, 1.33; P = .43), and any inflammatory event (HR, 0.93; P = .85). In a subgroup analysis, which compared the impact of DMT discontinuation between patients over the age of 45 years and those aged 45 years and younger, the researchers observed a statistically significant difference in effect of discontinuation on time to clinical relapse (P = .032), time to MRI event (P = .013), and time to any inflammatory event (P = .0005), all favoring patients over the age of 45 years.

“This finding makes sense since age has been reported as one of the factors that negatively impacts on the inflammatory activity in patients with RRMS,” Dr. Yano said. “However, our study is the first study [to find] that the impact of discontinuing DMT on RRMS patient prognosis may differ based on the age at the discontinuation. In short, stopping DMT at a younger age has a statistically significant higher risk on inflammatory activities, compared to [stopping DMT at an] older age.”

He acknowledged certain limitations of the study, including its small sample size and single-center design. However, Dr. Yano said that a key strength of the analysis was the inclusion of MRI activity prior to DMT as the definition of stable state, “which is an integral piece of information when physicians and patients consider DMT discontinuation in a ‘real world’ clinical setting. We also used MRI activity as an outcome measure, which is lacking in prior discontinuation studies.”

Dr. Yano reported that he has received a research grant from Yoshida Scholarship Foundation in Japan. His coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Yano H et al. ACTRIMS Forum 2019, Poster 061.

DALLAS – Patients with relapsing emitting multiple sclerosis who discontinued treatment after a period of disease inactivity had a similar time to next event, compared with those who remained on treatment, results from a single-center study showed.

In addition, being over the age of 45 years was associated with a better disease course after treatment discontinuation.

“Being clinically and radiologically stable for more than 2 years can be a potential milestone to regard the discontinuation of DMT [disease-modifying therapy] as a reasonable option in a subset of patients, especially patients who are nondisabled,” lead study author Hajime Yano, MD, said in an interview at the Americas Committee for Treatment and Research in Multiple Sclerosis.

According to Dr. Yano, a research fellow at the Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center in Boston, relapsing remitting multiple sclerosis (RRMS) patients without relapse for long periods on treatment may consider discontinuing DMT, but there is limited information regarding the impact of discontinuation, especially in terms of MRI activity.

In an effort to investigate the impact of DMT discontinuation on clinical and radiologic outcomes in RRMS patients, he and his colleagues identified 70 patients from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB) study, which was initiated in 2000 and has enrolled more than 2,400 patients cared for at the Partners Multiple Sclerosis Center. Relapse date, symptoms, and Expanded Disability Status Scale (EDSS) were evaluated at 6-month intervals for each patient during the time of clinic visits by the treating neurologist. Additionally, brain MRIs were performed annually.

Next, the researchers matched the patients with 70 patients who remained on DMT identified by age, sex, treatment, treatment duration, disease duration, and EDSS. They used univariate and multivariable Cox proportional hazard models to test the differences between DMT discontinuation status with time to clinical relapse, MRI event, disability progression, and any inflammatory event (either clinical relapse or MRI event).

The mean age of patients was 45 years, 87% were female, their mean disease duration was about 13 years, and they had been receiving treatment for a mean of about 6 years. In adjusted analyses, the 70 pairs of patients who discontinued DMT and patients who continued DMT had similar outcomes in time to clinical relapse (hazard ratio, 0.93; P = .84), MRI event (HR, 1.01; P = .98), disability progression (HR, 1.33; P = .43), and any inflammatory event (HR, 0.93; P = .85). In a subgroup analysis, which compared the impact of DMT discontinuation between patients over the age of 45 years and those aged 45 years and younger, the researchers observed a statistically significant difference in effect of discontinuation on time to clinical relapse (P = .032), time to MRI event (P = .013), and time to any inflammatory event (P = .0005), all favoring patients over the age of 45 years.

“This finding makes sense since age has been reported as one of the factors that negatively impacts on the inflammatory activity in patients with RRMS,” Dr. Yano said. “However, our study is the first study [to find] that the impact of discontinuing DMT on RRMS patient prognosis may differ based on the age at the discontinuation. In short, stopping DMT at a younger age has a statistically significant higher risk on inflammatory activities, compared to [stopping DMT at an] older age.”

He acknowledged certain limitations of the study, including its small sample size and single-center design. However, Dr. Yano said that a key strength of the analysis was the inclusion of MRI activity prior to DMT as the definition of stable state, “which is an integral piece of information when physicians and patients consider DMT discontinuation in a ‘real world’ clinical setting. We also used MRI activity as an outcome measure, which is lacking in prior discontinuation studies.”

Dr. Yano reported that he has received a research grant from Yoshida Scholarship Foundation in Japan. His coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Yano H et al. ACTRIMS Forum 2019, Poster 061.

DALLAS – Patients with relapsing emitting multiple sclerosis who discontinued treatment after a period of disease inactivity had a similar time to next event, compared with those who remained on treatment, results from a single-center study showed.

In addition, being over the age of 45 years was associated with a better disease course after treatment discontinuation.

“Being clinically and radiologically stable for more than 2 years can be a potential milestone to regard the discontinuation of DMT [disease-modifying therapy] as a reasonable option in a subset of patients, especially patients who are nondisabled,” lead study author Hajime Yano, MD, said in an interview at the Americas Committee for Treatment and Research in Multiple Sclerosis.

According to Dr. Yano, a research fellow at the Ann Romney Center for Neurologic Diseases and Partners Multiple Sclerosis Center in Boston, relapsing remitting multiple sclerosis (RRMS) patients without relapse for long periods on treatment may consider discontinuing DMT, but there is limited information regarding the impact of discontinuation, especially in terms of MRI activity.

In an effort to investigate the impact of DMT discontinuation on clinical and radiologic outcomes in RRMS patients, he and his colleagues identified 70 patients from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB) study, which was initiated in 2000 and has enrolled more than 2,400 patients cared for at the Partners Multiple Sclerosis Center. Relapse date, symptoms, and Expanded Disability Status Scale (EDSS) were evaluated at 6-month intervals for each patient during the time of clinic visits by the treating neurologist. Additionally, brain MRIs were performed annually.

Next, the researchers matched the patients with 70 patients who remained on DMT identified by age, sex, treatment, treatment duration, disease duration, and EDSS. They used univariate and multivariable Cox proportional hazard models to test the differences between DMT discontinuation status with time to clinical relapse, MRI event, disability progression, and any inflammatory event (either clinical relapse or MRI event).

The mean age of patients was 45 years, 87% were female, their mean disease duration was about 13 years, and they had been receiving treatment for a mean of about 6 years. In adjusted analyses, the 70 pairs of patients who discontinued DMT and patients who continued DMT had similar outcomes in time to clinical relapse (hazard ratio, 0.93; P = .84), MRI event (HR, 1.01; P = .98), disability progression (HR, 1.33; P = .43), and any inflammatory event (HR, 0.93; P = .85). In a subgroup analysis, which compared the impact of DMT discontinuation between patients over the age of 45 years and those aged 45 years and younger, the researchers observed a statistically significant difference in effect of discontinuation on time to clinical relapse (P = .032), time to MRI event (P = .013), and time to any inflammatory event (P = .0005), all favoring patients over the age of 45 years.

“This finding makes sense since age has been reported as one of the factors that negatively impacts on the inflammatory activity in patients with RRMS,” Dr. Yano said. “However, our study is the first study [to find] that the impact of discontinuing DMT on RRMS patient prognosis may differ based on the age at the discontinuation. In short, stopping DMT at a younger age has a statistically significant higher risk on inflammatory activities, compared to [stopping DMT at an] older age.”

He acknowledged certain limitations of the study, including its small sample size and single-center design. However, Dr. Yano said that a key strength of the analysis was the inclusion of MRI activity prior to DMT as the definition of stable state, “which is an integral piece of information when physicians and patients consider DMT discontinuation in a ‘real world’ clinical setting. We also used MRI activity as an outcome measure, which is lacking in prior discontinuation studies.”

Dr. Yano reported that he has received a research grant from Yoshida Scholarship Foundation in Japan. His coauthors reported having numerous financial ties to industry.

[email protected]

SOURCE: Yano H et al. ACTRIMS Forum 2019, Poster 061.

DALLAS – An iPad-based series of neuroperformance tests and patient-reported outcomes along with fully automated MRI analysis may facilitate the clinical evaluation of patients with multiple sclerosis, according to research described at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

An analysis of data collected using these methods found that patient-reported outcomes and MRI measures correlate with neuroperformance test results, said Laura Baldassari, MD, a clinical neuroimmunology fellow at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic. Such assessments “could potentially enable us to better tune in to disability worsening and treatment response in our patients.”

The Multiple Sclerosis Performance Test (MSPT) collects patient-reported outcomes and tests patients’ processing speed, contrast sensitivity, manual dexterity, and walking speed. The MSPT is designed for supervised or independent administration with an assistant and has been “incorporated into routine clinical care at the Mellen Center,” Dr. Baldassari said. Before seeing their provider, patients complete the MSPT with a biomedical assistant, which usually takes 30-40 minutes. The data are scored instantly and “integrated into the electronic medical record for use during the clinical encounter.”

Dr. Baldassari and her research colleagues analyzed associations between the neuroperformance metrics, patient-reported outcome measures, and quantitative MRI metrics. The analysis included 976 patients who completed the MSPT between December 2015 and December 2017 and had an MRI within 3 months of a clinical encounter. T2 lesion volume, normalized whole brain volume or whole brain fraction, thalamic volume, and cross-sectional upper cervical spinal cord area at the level of C2 on MRI were calculated using a fully automated method.

Patient-reported outcomes included Quality of Life in Neurological Disorders (Neuro-QoL) upper and lower extremity function, Patient-Reported Outcomes Measurement Information System (PROMIS) physical, and Patient Determined Disease Steps (PDDS).

The researchers used Spearman correlation coefficients to examine the relationships between each neuroperformance test, patient-reported outcome, and MRI measure. Linear regression models determined which clinical demographic, patient-reported outcome, or MRI characteristic predicted neuroperformance test results.

Patients had a mean age of about 48 years, and the population was predominantly female and white with relapsing remitting MS.

“There were significant correlations between all neuroperformance tests and all patient-reported outcomes except for the contrast sensitivity test and PROMIS physical,” Dr. Baldassari said. “The processing speed test was most strongly correlated with the PDDS as well as the Neuro-QoL lower extremity. The contrast sensitivity test was correlated with Neuro-QoL lower extremity as well.” The manual dexterity test correlated with PDDS and Neuro-QoL upper and lower extremity and the walking speed test correlated with PDDS and Neuro-QoL lower extremity.

“With worsening self-reported functions, these neuroperformance test results demonstrated impairment as well,” she said.

The neuroperformance tests and all MRI metrics had significant, moderate correlations. “The strongest correlations here are between the processing speed test and whole brain fraction and T2 lesion volume; contrast sensitivity and T2 lesion volume, whole brain fraction, and thalamic volume; manual dexterity test and T2 lesion volume and whole brain fraction; and walking speed test and whole brain fraction and cord area,” she said.

“The strongest predictors of each neuroperformance test varied, which highlights the unique complementary contribution of each patient-reported outcome measure and MRI metric to the complex domains of disability in MS,” Dr. Baldassari said.

Comprehensive, quantitative MS assessments may lead to detailed patient profiles, which could support more precise clinical care and observational studies. In future studies, the researchers plan to examine how these measures relate over time.

The MSPT was developed by the Cleveland Clinic in partnership with Biogen. Dr. Baldassari reported receiving funding through the National Multiple Sclerosis Society and personal fees for serving on a scientific advisory board for Teva. His coauthors’ disclosures included the contribution of intellectual property to the MSPT, for which they could receive royalties.

[email protected]

SOURCE: Baldassari L et al. ACTRIMS Forum 2019, Abstract 32.

DALLAS – An iPad-based series of neuroperformance tests and patient-reported outcomes along with fully automated MRI analysis may facilitate the clinical evaluation of patients with multiple sclerosis, according to research described at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

An analysis of data collected using these methods found that patient-reported outcomes and MRI measures correlate with neuroperformance test results, said Laura Baldassari, MD, a clinical neuroimmunology fellow at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic. Such assessments “could potentially enable us to better tune in to disability worsening and treatment response in our patients.”

The Multiple Sclerosis Performance Test (MSPT) collects patient-reported outcomes and tests patients’ processing speed, contrast sensitivity, manual dexterity, and walking speed. The MSPT is designed for supervised or independent administration with an assistant and has been “incorporated into routine clinical care at the Mellen Center,” Dr. Baldassari said. Before seeing their provider, patients complete the MSPT with a biomedical assistant, which usually takes 30-40 minutes. The data are scored instantly and “integrated into the electronic medical record for use during the clinical encounter.”

Dr. Baldassari and her research colleagues analyzed associations between the neuroperformance metrics, patient-reported outcome measures, and quantitative MRI metrics. The analysis included 976 patients who completed the MSPT between December 2015 and December 2017 and had an MRI within 3 months of a clinical encounter. T2 lesion volume, normalized whole brain volume or whole brain fraction, thalamic volume, and cross-sectional upper cervical spinal cord area at the level of C2 on MRI were calculated using a fully automated method.

Patient-reported outcomes included Quality of Life in Neurological Disorders (Neuro-QoL) upper and lower extremity function, Patient-Reported Outcomes Measurement Information System (PROMIS) physical, and Patient Determined Disease Steps (PDDS).

The researchers used Spearman correlation coefficients to examine the relationships between each neuroperformance test, patient-reported outcome, and MRI measure. Linear regression models determined which clinical demographic, patient-reported outcome, or MRI characteristic predicted neuroperformance test results.

Patients had a mean age of about 48 years, and the population was predominantly female and white with relapsing remitting MS.

“There were significant correlations between all neuroperformance tests and all patient-reported outcomes except for the contrast sensitivity test and PROMIS physical,” Dr. Baldassari said. “The processing speed test was most strongly correlated with the PDDS as well as the Neuro-QoL lower extremity. The contrast sensitivity test was correlated with Neuro-QoL lower extremity as well.” The manual dexterity test correlated with PDDS and Neuro-QoL upper and lower extremity and the walking speed test correlated with PDDS and Neuro-QoL lower extremity.

“With worsening self-reported functions, these neuroperformance test results demonstrated impairment as well,” she said.

The neuroperformance tests and all MRI metrics had significant, moderate correlations. “The strongest correlations here are between the processing speed test and whole brain fraction and T2 lesion volume; contrast sensitivity and T2 lesion volume, whole brain fraction, and thalamic volume; manual dexterity test and T2 lesion volume and whole brain fraction; and walking speed test and whole brain fraction and cord area,” she said.

“The strongest predictors of each neuroperformance test varied, which highlights the unique complementary contribution of each patient-reported outcome measure and MRI metric to the complex domains of disability in MS,” Dr. Baldassari said.

Comprehensive, quantitative MS assessments may lead to detailed patient profiles, which could support more precise clinical care and observational studies. In future studies, the researchers plan to examine how these measures relate over time.

The MSPT was developed by the Cleveland Clinic in partnership with Biogen. Dr. Baldassari reported receiving funding through the National Multiple Sclerosis Society and personal fees for serving on a scientific advisory board for Teva. His coauthors’ disclosures included the contribution of intellectual property to the MSPT, for which they could receive royalties.

[email protected]

SOURCE: Baldassari L et al. ACTRIMS Forum 2019, Abstract 32.

DALLAS – An iPad-based series of neuroperformance tests and patient-reported outcomes along with fully automated MRI analysis may facilitate the clinical evaluation of patients with multiple sclerosis, according to research described at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

An analysis of data collected using these methods found that patient-reported outcomes and MRI measures correlate with neuroperformance test results, said Laura Baldassari, MD, a clinical neuroimmunology fellow at the Mellen Center for Multiple Sclerosis at the Cleveland Clinic. Such assessments “could potentially enable us to better tune in to disability worsening and treatment response in our patients.”

The Multiple Sclerosis Performance Test (MSPT) collects patient-reported outcomes and tests patients’ processing speed, contrast sensitivity, manual dexterity, and walking speed. The MSPT is designed for supervised or independent administration with an assistant and has been “incorporated into routine clinical care at the Mellen Center,” Dr. Baldassari said. Before seeing their provider, patients complete the MSPT with a biomedical assistant, which usually takes 30-40 minutes. The data are scored instantly and “integrated into the electronic medical record for use during the clinical encounter.”

Dr. Baldassari and her research colleagues analyzed associations between the neuroperformance metrics, patient-reported outcome measures, and quantitative MRI metrics. The analysis included 976 patients who completed the MSPT between December 2015 and December 2017 and had an MRI within 3 months of a clinical encounter. T2 lesion volume, normalized whole brain volume or whole brain fraction, thalamic volume, and cross-sectional upper cervical spinal cord area at the level of C2 on MRI were calculated using a fully automated method.

Patient-reported outcomes included Quality of Life in Neurological Disorders (Neuro-QoL) upper and lower extremity function, Patient-Reported Outcomes Measurement Information System (PROMIS) physical, and Patient Determined Disease Steps (PDDS).

The researchers used Spearman correlation coefficients to examine the relationships between each neuroperformance test, patient-reported outcome, and MRI measure. Linear regression models determined which clinical demographic, patient-reported outcome, or MRI characteristic predicted neuroperformance test results.

Patients had a mean age of about 48 years, and the population was predominantly female and white with relapsing remitting MS.

“There were significant correlations between all neuroperformance tests and all patient-reported outcomes except for the contrast sensitivity test and PROMIS physical,” Dr. Baldassari said. “The processing speed test was most strongly correlated with the PDDS as well as the Neuro-QoL lower extremity. The contrast sensitivity test was correlated with Neuro-QoL lower extremity as well.” The manual dexterity test correlated with PDDS and Neuro-QoL upper and lower extremity and the walking speed test correlated with PDDS and Neuro-QoL lower extremity.

“With worsening self-reported functions, these neuroperformance test results demonstrated impairment as well,” she said.

The neuroperformance tests and all MRI metrics had significant, moderate correlations. “The strongest correlations here are between the processing speed test and whole brain fraction and T2 lesion volume; contrast sensitivity and T2 lesion volume, whole brain fraction, and thalamic volume; manual dexterity test and T2 lesion volume and whole brain fraction; and walking speed test and whole brain fraction and cord area,” she said.

“The strongest predictors of each neuroperformance test varied, which highlights the unique complementary contribution of each patient-reported outcome measure and MRI metric to the complex domains of disability in MS,” Dr. Baldassari said.

Comprehensive, quantitative MS assessments may lead to detailed patient profiles, which could support more precise clinical care and observational studies. In future studies, the researchers plan to examine how these measures relate over time.

The MSPT was developed by the Cleveland Clinic in partnership with Biogen. Dr. Baldassari reported receiving funding through the National Multiple Sclerosis Society and personal fees for serving on a scientific advisory board for Teva. His coauthors’ disclosures included the contribution of intellectual property to the MSPT, for which they could receive royalties.

[email protected]

SOURCE: Baldassari L et al. ACTRIMS Forum 2019, Abstract 32.

DALLAS – The way Lilyana Amezcua, MD, sees it, clinicians should view race and ethnicity as health disparities when assessing individuals with multiple sclerosis.

Whites are predominately affected with MS, “but we have seen changing demographics,” said Dr. Amezcua, of the University of Southern California MS Comprehensive Care and Research Group. “Why are African Americans now at higher risk ... and why do African Americans appear to have more severe disease? Is it a biological difference ... or is it because of poor access” to health care?

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Amezcua delivered a presentation entitled “Effect of Race and Ethnicity on MS Presentation and Disease Course.” She called on researchers in the field “to not just take race and ethnicity as any small variable. We need to be cognizant and use the correct methodology, depending on what [question] we want to answer. We need to better define how we ascertain race, how we ascertain ethnicity.”

Dr. Amezcua, who is also the MS fellowship program director at the Keck School of Medicine, disclosed that she receives funding from the National MS Society, the National Institutes of Health, the California Community Foundation, and Biogen.

[email protected]

DALLAS – The way Lilyana Amezcua, MD, sees it, clinicians should view race and ethnicity as health disparities when assessing individuals with multiple sclerosis.

Whites are predominately affected with MS, “but we have seen changing demographics,” said Dr. Amezcua, of the University of Southern California MS Comprehensive Care and Research Group. “Why are African Americans now at higher risk ... and why do African Americans appear to have more severe disease? Is it a biological difference ... or is it because of poor access” to health care?

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Amezcua delivered a presentation entitled “Effect of Race and Ethnicity on MS Presentation and Disease Course.” She called on researchers in the field “to not just take race and ethnicity as any small variable. We need to be cognizant and use the correct methodology, depending on what [question] we want to answer. We need to better define how we ascertain race, how we ascertain ethnicity.”

Dr. Amezcua, who is also the MS fellowship program director at the Keck School of Medicine, disclosed that she receives funding from the National MS Society, the National Institutes of Health, the California Community Foundation, and Biogen.

[email protected]

DALLAS – The way Lilyana Amezcua, MD, sees it, clinicians should view race and ethnicity as health disparities when assessing individuals with multiple sclerosis.

Whites are predominately affected with MS, “but we have seen changing demographics,” said Dr. Amezcua, of the University of Southern California MS Comprehensive Care and Research Group. “Why are African Americans now at higher risk ... and why do African Americans appear to have more severe disease? Is it a biological difference ... or is it because of poor access” to health care?

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Amezcua delivered a presentation entitled “Effect of Race and Ethnicity on MS Presentation and Disease Course.” She called on researchers in the field “to not just take race and ethnicity as any small variable. We need to be cognizant and use the correct methodology, depending on what [question] we want to answer. We need to better define how we ascertain race, how we ascertain ethnicity.”

Dr. Amezcua, who is also the MS fellowship program director at the Keck School of Medicine, disclosed that she receives funding from the National MS Society, the National Institutes of Health, the California Community Foundation, and Biogen.

[email protected]

DALLAS – Ublituximab, a novel anti-CD20 antibody, rapidly and robustly depletes B cells in patients with relapsing forms of multiple sclerosis (MS), according to phase 2 trial results presented at ACTRIMS Forum 2019. Patients treated with the investigational therapy had reduced MRI activity and relapse rates during the 48-week trial, and the treatment was well tolerated, researchers said.

The monoclonal antibody targets a unique epitope on the CD20 antigen and is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity, said presenting author Edward Fox, MD, PhD, director of the MS Clinic of Central Texas, Round Rock. Ublituximab’s potency “may offer a benefit over currently available anti-CD20s in terms of lower doses and shorter infusion times,” Dr. Fox and his research colleagues said.

To assess the optimal dose, infusion time, safety, and tolerability of ublituximab in relapsing MS, investigators conducted a phase 2, multicenter study. The trial included 48 patients with relapsing MS; 65% were female. Patients’ average age was 40 years and average disease duration was 7.7 years. The researchers included patients with one or more confirmed relapse in the past year, two relapses in the past 2 years, or at least one active gadolinium-enhancing T1 lesion. The primary endpoint was the percentage of patients with at least a 95% reduction in peripheral CD19+ B cells within 2 weeks after the second infusion on day 15.

For their first infusions, patients received 150 mg of ublituximab over an infusion time of 1, 2, 3, or 4 hours. On day 15, patients received 450 mg or 600 mg of ublituximab over an infusion time of 1, 1.5, or 3 hours. At week 24, patients received 450 mg or 650 mg of ublituximab infused over 1 hour or 1.5 hours.

All patients met the primary endpoint of greater than 95% B-cell depletion between baseline and week 4. Median B-cell depletion was 99% at week 4, and this effect was maintained at weeks 24 and 48.

The researchers detected no T1 gadolinium-enhancing lesions at week 24 or week 48, and total T2 lesion volume decreased by 10.6% between baseline and week 48.

The most frequent adverse events were infusion-related reactions, which occurred in 48% of patients and were more common with the first infusion, particularly when the infusion time was less than 4 hours. All of the infusion-related reactions were grade 1 or 2. One grade 3 serious adverse event of fatigue was considered possibly related to ublituximab. No patients withdrew from the study because of drug-related adverse events. At week 48, 93% of the patients were relapse free, 7% had 24-week confirmed disability progression, and 17% had confirmed disability improvement.

TG Therapeutics, the company developing ublituximab, is evaluating the therapy in phase 3 trials known as ULTIMATE I and 2. The phase 3 trials are using the 450-mg dose with a first dose of 150 mg delivered over 4 hours.

Dr. Fox has disclosed research support from TG Therapeutics and other pharmaceutical companies and working as a consultant and speaker for TG Therapeutics and other companies.

[email protected]

SOURCE: Fox E et al. ACTRIMS Forum 2019, Abstract 66.

DALLAS – Ublituximab, a novel anti-CD20 antibody, rapidly and robustly depletes B cells in patients with relapsing forms of multiple sclerosis (MS), according to phase 2 trial results presented at ACTRIMS Forum 2019. Patients treated with the investigational therapy had reduced MRI activity and relapse rates during the 48-week trial, and the treatment was well tolerated, researchers said.

The monoclonal antibody targets a unique epitope on the CD20 antigen and is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity, said presenting author Edward Fox, MD, PhD, director of the MS Clinic of Central Texas, Round Rock. Ublituximab’s potency “may offer a benefit over currently available anti-CD20s in terms of lower doses and shorter infusion times,” Dr. Fox and his research colleagues said.

To assess the optimal dose, infusion time, safety, and tolerability of ublituximab in relapsing MS, investigators conducted a phase 2, multicenter study. The trial included 48 patients with relapsing MS; 65% were female. Patients’ average age was 40 years and average disease duration was 7.7 years. The researchers included patients with one or more confirmed relapse in the past year, two relapses in the past 2 years, or at least one active gadolinium-enhancing T1 lesion. The primary endpoint was the percentage of patients with at least a 95% reduction in peripheral CD19+ B cells within 2 weeks after the second infusion on day 15.

For their first infusions, patients received 150 mg of ublituximab over an infusion time of 1, 2, 3, or 4 hours. On day 15, patients received 450 mg or 600 mg of ublituximab over an infusion time of 1, 1.5, or 3 hours. At week 24, patients received 450 mg or 650 mg of ublituximab infused over 1 hour or 1.5 hours.

All patients met the primary endpoint of greater than 95% B-cell depletion between baseline and week 4. Median B-cell depletion was 99% at week 4, and this effect was maintained at weeks 24 and 48.

The researchers detected no T1 gadolinium-enhancing lesions at week 24 or week 48, and total T2 lesion volume decreased by 10.6% between baseline and week 48.

The most frequent adverse events were infusion-related reactions, which occurred in 48% of patients and were more common with the first infusion, particularly when the infusion time was less than 4 hours. All of the infusion-related reactions were grade 1 or 2. One grade 3 serious adverse event of fatigue was considered possibly related to ublituximab. No patients withdrew from the study because of drug-related adverse events. At week 48, 93% of the patients were relapse free, 7% had 24-week confirmed disability progression, and 17% had confirmed disability improvement.

TG Therapeutics, the company developing ublituximab, is evaluating the therapy in phase 3 trials known as ULTIMATE I and 2. The phase 3 trials are using the 450-mg dose with a first dose of 150 mg delivered over 4 hours.

Dr. Fox has disclosed research support from TG Therapeutics and other pharmaceutical companies and working as a consultant and speaker for TG Therapeutics and other companies.

[email protected]

SOURCE: Fox E et al. ACTRIMS Forum 2019, Abstract 66.

DALLAS – Ublituximab, a novel anti-CD20 antibody, rapidly and robustly depletes B cells in patients with relapsing forms of multiple sclerosis (MS), according to phase 2 trial results presented at ACTRIMS Forum 2019. Patients treated with the investigational therapy had reduced MRI activity and relapse rates during the 48-week trial, and the treatment was well tolerated, researchers said.

The monoclonal antibody targets a unique epitope on the CD20 antigen and is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity, said presenting author Edward Fox, MD, PhD, director of the MS Clinic of Central Texas, Round Rock. Ublituximab’s potency “may offer a benefit over currently available anti-CD20s in terms of lower doses and shorter infusion times,” Dr. Fox and his research colleagues said.

To assess the optimal dose, infusion time, safety, and tolerability of ublituximab in relapsing MS, investigators conducted a phase 2, multicenter study. The trial included 48 patients with relapsing MS; 65% were female. Patients’ average age was 40 years and average disease duration was 7.7 years. The researchers included patients with one or more confirmed relapse in the past year, two relapses in the past 2 years, or at least one active gadolinium-enhancing T1 lesion. The primary endpoint was the percentage of patients with at least a 95% reduction in peripheral CD19+ B cells within 2 weeks after the second infusion on day 15.

For their first infusions, patients received 150 mg of ublituximab over an infusion time of 1, 2, 3, or 4 hours. On day 15, patients received 450 mg or 600 mg of ublituximab over an infusion time of 1, 1.5, or 3 hours. At week 24, patients received 450 mg or 650 mg of ublituximab infused over 1 hour or 1.5 hours.

All patients met the primary endpoint of greater than 95% B-cell depletion between baseline and week 4. Median B-cell depletion was 99% at week 4, and this effect was maintained at weeks 24 and 48.

The researchers detected no T1 gadolinium-enhancing lesions at week 24 or week 48, and total T2 lesion volume decreased by 10.6% between baseline and week 48.

The most frequent adverse events were infusion-related reactions, which occurred in 48% of patients and were more common with the first infusion, particularly when the infusion time was less than 4 hours. All of the infusion-related reactions were grade 1 or 2. One grade 3 serious adverse event of fatigue was considered possibly related to ublituximab. No patients withdrew from the study because of drug-related adverse events. At week 48, 93% of the patients were relapse free, 7% had 24-week confirmed disability progression, and 17% had confirmed disability improvement.

TG Therapeutics, the company developing ublituximab, is evaluating the therapy in phase 3 trials known as ULTIMATE I and 2. The phase 3 trials are using the 450-mg dose with a first dose of 150 mg delivered over 4 hours.

Dr. Fox has disclosed research support from TG Therapeutics and other pharmaceutical companies and working as a consultant and speaker for TG Therapeutics and other companies.

[email protected]

SOURCE: Fox E et al. ACTRIMS Forum 2019, Abstract 66.