Multiple Sclerosis

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.

koakes@mdedge.com

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.

koakes@mdedge.com

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.

koakes@mdedge.com

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.

jremaly@mdedge.com

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.

jremaly@mdedge.com

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.

jremaly@mdedge.com

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.

dbrunk@mdedge.com

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.

dbrunk@mdedge.com

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.

dbrunk@mdedge.com

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.

jremaly@mdedge.com

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.

jremaly@mdedge.com

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.

jremaly@mdedge.com

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.

dbrunk@mdedge.com

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.

dbrunk@mdedge.com

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.

dbrunk@mdedge.com

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.

jremaly@mdedge.com

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.

jremaly@mdedge.com

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.

jremaly@mdedge.com

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

DALLAS – Patients with multiple sclerosis (MS) have elevated levels of specific clusters of cerebrospinal fluid (CSF) biomarkers related to astrocytes and microglia that correlated with disease severity in a blinded analysis of more than 1,000 proteins from the CSF of more than 400 patients with neuroimmunologic disease and healthy volunteers.

Jake Remaly/MDedge News

Previous studies have indicated that aberrant activation of astrocytes and microglia underlies disability progression in older patients with MS, but researchers have lacked biomarkers of these processes in living subjects. In a presentation at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Ruturaj R. Masvekar, PhD, described developing biomarkers of CNS cell–specific processes and examining how they relate to MS disability progression. Dr. Masvekar, a researcher at the National Institute of Allergy and Infectious Diseases, and his coinvestigators used a modified DNA aptamer assay to measure proteins in the CSF of 431 patients with neuroimmunologic diseases and healthy volunteers, followed by variable cluster analysis and in vitro modeling to define 64 clusters of CSF biomarkers that relate to CNS cell types.

The study included 42 healthy donors, 20 patients with clinically isolated syndrome, 57 patients with noninflammatory neurologic disorders, 127 patients with relapsing-remitting MS, 72 patients with secondary progressive MS, and 113 patients with primary progressive MS. In a training cohort of 217 participants, the researchers assessed how biomarkers differed between the diagnostic categories. The researchers then validated the results in an independent cohort of 214 participants.

One astrocyte-related cluster (MMP7, SERPINA3, GZMA, and CLIC1) and one microglia-related cluster (DSG2 and TNFRSF25) was significantly elevated in all MS subgroups, compared with healthy controls and patients with noninflammatory neurologic disorders.

In addition, these clusters “significantly correlated with clinical measures of disability, CNS tissue destruction, and MS severity,” Dr. Masvekar said.

The microglial cluster was significantly elevated in all MS subgroups, whereas neuronal endothelial, astrocytic, and oligodendroglial biomarker clusters were elevated only in patients with progressive MS.

“Microglial activation is present in all stages of MS, while toxic astrogliosis increases with MS duration, concomitantly with neuronal and oligodendroglial degeneration,” Dr. Masvekar said. “Microglial activation and toxic astrogliosis likely partake in CNS tissue destruction and enhance MS severity.”

This study, which was recently published in Multiple Sclerosis and Related Disorders (2019 Feb;28:34-43), was supported by the intramural research program at NIAID.

jremaly@mdedge.com

SOURCE: Masvekar RR et al. ACTRIMS Forum 2019, Abstract 281.

DALLAS – Patients with multiple sclerosis (MS) have elevated levels of specific clusters of cerebrospinal fluid (CSF) biomarkers related to astrocytes and microglia that correlated with disease severity in a blinded analysis of more than 1,000 proteins from the CSF of more than 400 patients with neuroimmunologic disease and healthy volunteers.

Jake Remaly/MDedge News

Previous studies have indicated that aberrant activation of astrocytes and microglia underlies disability progression in older patients with MS, but researchers have lacked biomarkers of these processes in living subjects. In a presentation at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Ruturaj R. Masvekar, PhD, described developing biomarkers of CNS cell–specific processes and examining how they relate to MS disability progression. Dr. Masvekar, a researcher at the National Institute of Allergy and Infectious Diseases, and his coinvestigators used a modified DNA aptamer assay to measure proteins in the CSF of 431 patients with neuroimmunologic diseases and healthy volunteers, followed by variable cluster analysis and in vitro modeling to define 64 clusters of CSF biomarkers that relate to CNS cell types.

The study included 42 healthy donors, 20 patients with clinically isolated syndrome, 57 patients with noninflammatory neurologic disorders, 127 patients with relapsing-remitting MS, 72 patients with secondary progressive MS, and 113 patients with primary progressive MS. In a training cohort of 217 participants, the researchers assessed how biomarkers differed between the diagnostic categories. The researchers then validated the results in an independent cohort of 214 participants.

One astrocyte-related cluster (MMP7, SERPINA3, GZMA, and CLIC1) and one microglia-related cluster (DSG2 and TNFRSF25) was significantly elevated in all MS subgroups, compared with healthy controls and patients with noninflammatory neurologic disorders.

In addition, these clusters “significantly correlated with clinical measures of disability, CNS tissue destruction, and MS severity,” Dr. Masvekar said.

The microglial cluster was significantly elevated in all MS subgroups, whereas neuronal endothelial, astrocytic, and oligodendroglial biomarker clusters were elevated only in patients with progressive MS.

“Microglial activation is present in all stages of MS, while toxic astrogliosis increases with MS duration, concomitantly with neuronal and oligodendroglial degeneration,” Dr. Masvekar said. “Microglial activation and toxic astrogliosis likely partake in CNS tissue destruction and enhance MS severity.”

This study, which was recently published in Multiple Sclerosis and Related Disorders (2019 Feb;28:34-43), was supported by the intramural research program at NIAID.

jremaly@mdedge.com

SOURCE: Masvekar RR et al. ACTRIMS Forum 2019, Abstract 281.

DALLAS – Patients with multiple sclerosis (MS) have elevated levels of specific clusters of cerebrospinal fluid (CSF) biomarkers related to astrocytes and microglia that correlated with disease severity in a blinded analysis of more than 1,000 proteins from the CSF of more than 400 patients with neuroimmunologic disease and healthy volunteers.

Jake Remaly/MDedge News

Previous studies have indicated that aberrant activation of astrocytes and microglia underlies disability progression in older patients with MS, but researchers have lacked biomarkers of these processes in living subjects. In a presentation at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Ruturaj R. Masvekar, PhD, described developing biomarkers of CNS cell–specific processes and examining how they relate to MS disability progression. Dr. Masvekar, a researcher at the National Institute of Allergy and Infectious Diseases, and his coinvestigators used a modified DNA aptamer assay to measure proteins in the CSF of 431 patients with neuroimmunologic diseases and healthy volunteers, followed by variable cluster analysis and in vitro modeling to define 64 clusters of CSF biomarkers that relate to CNS cell types.

The study included 42 healthy donors, 20 patients with clinically isolated syndrome, 57 patients with noninflammatory neurologic disorders, 127 patients with relapsing-remitting MS, 72 patients with secondary progressive MS, and 113 patients with primary progressive MS. In a training cohort of 217 participants, the researchers assessed how biomarkers differed between the diagnostic categories. The researchers then validated the results in an independent cohort of 214 participants.

One astrocyte-related cluster (MMP7, SERPINA3, GZMA, and CLIC1) and one microglia-related cluster (DSG2 and TNFRSF25) was significantly elevated in all MS subgroups, compared with healthy controls and patients with noninflammatory neurologic disorders.

In addition, these clusters “significantly correlated with clinical measures of disability, CNS tissue destruction, and MS severity,” Dr. Masvekar said.

The microglial cluster was significantly elevated in all MS subgroups, whereas neuronal endothelial, astrocytic, and oligodendroglial biomarker clusters were elevated only in patients with progressive MS.

“Microglial activation is present in all stages of MS, while toxic astrogliosis increases with MS duration, concomitantly with neuronal and oligodendroglial degeneration,” Dr. Masvekar said. “Microglial activation and toxic astrogliosis likely partake in CNS tissue destruction and enhance MS severity.”

This study, which was recently published in Multiple Sclerosis and Related Disorders (2019 Feb;28:34-43), was supported by the intramural research program at NIAID.

jremaly@mdedge.com

SOURCE: Masvekar RR et al. ACTRIMS Forum 2019, Abstract 281.

DALLAS – In 2 years of follow-up, about 43% of U.S. patients diagnosed with multiple sclerosis (MS) had not received disease-modifying drug (DMD) therapy, a rate that is consistent with other published studies.

The finding comes from a retrospective analysis of claims data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “This rate of DMD treatment merits further exploration given that evidence suggests the importance of early DMD treatment initiation in patients with a confirmed diagnosis of relapsing forms of MS to help optimize the benefits of treatment,” Amy L. Phillips, PharmD, a study author, said in an interview in advance of the meeting.

Little is known about current DMD treatment patterns in U.S. patients with multiple sclerosis following an increase in the number of available DMDs in recent years, according to Dr. Phillips of the department of health economics and outcomes research at EMD Serono.

“Most previous studies have focused on self-injectable DMDs or self-injectable and infusion DMDs,” she said. “Information about the treatment patterns including oral DMDs is scarce, particularly in large population samples. The objective of our study was to describe treatment patterns and sequences of therapy among U.S. patients with MS newly initiating DMD treatment between Jan. 1, 2011 and June 30, 2015.”

Dr. Phillips, lead study author Jacqueline A. Nicholas, MD, MPH, of the OhioHealth Multiple Sclerosis Center, and their colleagues used data from the IQVIA RWD Adjudicated Claims database to identify patients who had at least two medical claims with a MS diagnosis and at least one DMD claim during the study period. Other eligibility criteria included continuous eligibility with commercial insurance 1 year before (baseline period) and 2 years after (follow-up period) initiation of the DMD, no evidence of DMD use during the baseline period, and being aged between 18 and 63 years.

Of 63,946 diagnostically eligible patients, 36,175 (57%) had a claim for a DMD. The researchers reported findings from 8,251 patients who met all of the eligibility criteria. Their mean age was 43 years, 76% were female, and the mean number of DMDs over 2 years among newly treated patients was 1.27.

The most common first-line DMD therapy was glatiramer acetate (GA, 38%), followed by intramuscular interferon beta (IM IFNb-1a, 14%), subcutaneous interferon beta (SC IFNb-1a, 14%), dimethyl fumarate (DMF, 14%), and fingolimod (9%). DMF was the most common second-line therapy (36%), followed by fingolimod (17%), GA (17%), SC IFNb-1a (8%), and IM IFNb-1a (7%).

“Numerous DMD treatment patterns observed in this study highlight the diverse patient and treatment needs,” Dr. Phillips said. “DMD treatment patterns in MS vary due to the heterogeneity of the disease, physician preferences, and patient needs and treatment goals. Patient-centered care and shared decision making has been shown to improve patient satisfaction and to encourage treatment adherence in MS.”

She acknowledged certain limitations of the study, including the fact that the analysis presents only the most common DMD treatment sequences observed in this patient population.

“Future analyses might examine less common DMD treatment sequences,” she said. “Also, more research is needed to understand how DMD treatment patterns and sequences change over time, and the factors that may be associated with DMD switching and treatment discontinuation.”

She also noted that the administrative claims data studied represent mostly patients with commercial health insurance, limiting the generalizability of the findings. Further, ICD-9 and ICD-10 codes do not distinguish between MS types.

Funding for the study was provided by EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the United States and Canada. Dr. Phillips is an employee of the company.

dbrunk@mdedge.com

SOURCE: Phillips A et al. ACTRIMS FORUM 2019, Abstract 001.

DALLAS – In 2 years of follow-up, about 43% of U.S. patients diagnosed with multiple sclerosis (MS) had not received disease-modifying drug (DMD) therapy, a rate that is consistent with other published studies.

The finding comes from a retrospective analysis of claims data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “This rate of DMD treatment merits further exploration given that evidence suggests the importance of early DMD treatment initiation in patients with a confirmed diagnosis of relapsing forms of MS to help optimize the benefits of treatment,” Amy L. Phillips, PharmD, a study author, said in an interview in advance of the meeting.

Little is known about current DMD treatment patterns in U.S. patients with multiple sclerosis following an increase in the number of available DMDs in recent years, according to Dr. Phillips of the department of health economics and outcomes research at EMD Serono.

“Most previous studies have focused on self-injectable DMDs or self-injectable and infusion DMDs,” she said. “Information about the treatment patterns including oral DMDs is scarce, particularly in large population samples. The objective of our study was to describe treatment patterns and sequences of therapy among U.S. patients with MS newly initiating DMD treatment between Jan. 1, 2011 and June 30, 2015.”

Dr. Phillips, lead study author Jacqueline A. Nicholas, MD, MPH, of the OhioHealth Multiple Sclerosis Center, and their colleagues used data from the IQVIA RWD Adjudicated Claims database to identify patients who had at least two medical claims with a MS diagnosis and at least one DMD claim during the study period. Other eligibility criteria included continuous eligibility with commercial insurance 1 year before (baseline period) and 2 years after (follow-up period) initiation of the DMD, no evidence of DMD use during the baseline period, and being aged between 18 and 63 years.

Of 63,946 diagnostically eligible patients, 36,175 (57%) had a claim for a DMD. The researchers reported findings from 8,251 patients who met all of the eligibility criteria. Their mean age was 43 years, 76% were female, and the mean number of DMDs over 2 years among newly treated patients was 1.27.

The most common first-line DMD therapy was glatiramer acetate (GA, 38%), followed by intramuscular interferon beta (IM IFNb-1a, 14%), subcutaneous interferon beta (SC IFNb-1a, 14%), dimethyl fumarate (DMF, 14%), and fingolimod (9%). DMF was the most common second-line therapy (36%), followed by fingolimod (17%), GA (17%), SC IFNb-1a (8%), and IM IFNb-1a (7%).

“Numerous DMD treatment patterns observed in this study highlight the diverse patient and treatment needs,” Dr. Phillips said. “DMD treatment patterns in MS vary due to the heterogeneity of the disease, physician preferences, and patient needs and treatment goals. Patient-centered care and shared decision making has been shown to improve patient satisfaction and to encourage treatment adherence in MS.”

She acknowledged certain limitations of the study, including the fact that the analysis presents only the most common DMD treatment sequences observed in this patient population.

“Future analyses might examine less common DMD treatment sequences,” she said. “Also, more research is needed to understand how DMD treatment patterns and sequences change over time, and the factors that may be associated with DMD switching and treatment discontinuation.”

She also noted that the administrative claims data studied represent mostly patients with commercial health insurance, limiting the generalizability of the findings. Further, ICD-9 and ICD-10 codes do not distinguish between MS types.

Funding for the study was provided by EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the United States and Canada. Dr. Phillips is an employee of the company.

dbrunk@mdedge.com

SOURCE: Phillips A et al. ACTRIMS FORUM 2019, Abstract 001.

DALLAS – In 2 years of follow-up, about 43% of U.S. patients diagnosed with multiple sclerosis (MS) had not received disease-modifying drug (DMD) therapy, a rate that is consistent with other published studies.

The finding comes from a retrospective analysis of claims data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “This rate of DMD treatment merits further exploration given that evidence suggests the importance of early DMD treatment initiation in patients with a confirmed diagnosis of relapsing forms of MS to help optimize the benefits of treatment,” Amy L. Phillips, PharmD, a study author, said in an interview in advance of the meeting.

Little is known about current DMD treatment patterns in U.S. patients with multiple sclerosis following an increase in the number of available DMDs in recent years, according to Dr. Phillips of the department of health economics and outcomes research at EMD Serono.

“Most previous studies have focused on self-injectable DMDs or self-injectable and infusion DMDs,” she said. “Information about the treatment patterns including oral DMDs is scarce, particularly in large population samples. The objective of our study was to describe treatment patterns and sequences of therapy among U.S. patients with MS newly initiating DMD treatment between Jan. 1, 2011 and June 30, 2015.”

Dr. Phillips, lead study author Jacqueline A. Nicholas, MD, MPH, of the OhioHealth Multiple Sclerosis Center, and their colleagues used data from the IQVIA RWD Adjudicated Claims database to identify patients who had at least two medical claims with a MS diagnosis and at least one DMD claim during the study period. Other eligibility criteria included continuous eligibility with commercial insurance 1 year before (baseline period) and 2 years after (follow-up period) initiation of the DMD, no evidence of DMD use during the baseline period, and being aged between 18 and 63 years.

Of 63,946 diagnostically eligible patients, 36,175 (57%) had a claim for a DMD. The researchers reported findings from 8,251 patients who met all of the eligibility criteria. Their mean age was 43 years, 76% were female, and the mean number of DMDs over 2 years among newly treated patients was 1.27.

The most common first-line DMD therapy was glatiramer acetate (GA, 38%), followed by intramuscular interferon beta (IM IFNb-1a, 14%), subcutaneous interferon beta (SC IFNb-1a, 14%), dimethyl fumarate (DMF, 14%), and fingolimod (9%). DMF was the most common second-line therapy (36%), followed by fingolimod (17%), GA (17%), SC IFNb-1a (8%), and IM IFNb-1a (7%).

“Numerous DMD treatment patterns observed in this study highlight the diverse patient and treatment needs,” Dr. Phillips said. “DMD treatment patterns in MS vary due to the heterogeneity of the disease, physician preferences, and patient needs and treatment goals. Patient-centered care and shared decision making has been shown to improve patient satisfaction and to encourage treatment adherence in MS.”

She acknowledged certain limitations of the study, including the fact that the analysis presents only the most common DMD treatment sequences observed in this patient population.

“Future analyses might examine less common DMD treatment sequences,” she said. “Also, more research is needed to understand how DMD treatment patterns and sequences change over time, and the factors that may be associated with DMD switching and treatment discontinuation.”

She also noted that the administrative claims data studied represent mostly patients with commercial health insurance, limiting the generalizability of the findings. Further, ICD-9 and ICD-10 codes do not distinguish between MS types.

Funding for the study was provided by EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the United States and Canada. Dr. Phillips is an employee of the company.

dbrunk@mdedge.com

SOURCE: Phillips A et al. ACTRIMS FORUM 2019, Abstract 001.

DALLAS – Biologic aging as measured by leukocyte telomere length (LTL) is associated with multiple sclerosis (MS) disability progression independent of chronological age, according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Shorter telomere length is associated with increased MS disability in cross-sectional and longitudinal analyses, said Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco. The results suggest that biologic aging may contribute to neurologic injury in MS and that “targeting aging-related mechanisms may be a potential therapeutic strategy,” said Dr. Krysko.

If validated, telomere length may be a biomarker that neurologists could use to guide decisions about MS treatment, said principal investigator Jennifer Graves, MD, PhD, also of UCSF.

“Factors leading to MS progression are not fully understood,” Dr. Krysko said. “But consistently, older chronological age has been associated with a faster time to disability milestones.” Aging may reduce remyelination capacity and alter immunologic responses. Telomere shortening, a marker of cellular aging, is “the ultimate biological clock.” It has been associated with cardiovascular disease, dementia, and autoimmune diseases, and one study found that patients with primary progressive MS have shorter telomere length, compared with controls.

To assess whether LTL is associated with clinical disability and brain volume in patients with MS, the researchers analyzed data from 516 adults with MS or clinically isolated syndrome in the EPIC cohort study at UCSF. Telomere length was measured on stored baseline DNA samples and expressed as the ratio of telomere to a single-copy gene.

The patients had an average age of 43 years, median disease duration of 6 years, and median Expanded Disability Status Scale (EDSS) score of 1.5; about 70% were women. The average telomere length was 0.97.

jremaly@mdedge.com

SOURCE: Krysko KM et al. ACTRIMS Forum 2019, Abstract 289.

DALLAS – Biologic aging as measured by leukocyte telomere length (LTL) is associated with multiple sclerosis (MS) disability progression independent of chronological age, according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Shorter telomere length is associated with increased MS disability in cross-sectional and longitudinal analyses, said Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco. The results suggest that biologic aging may contribute to neurologic injury in MS and that “targeting aging-related mechanisms may be a potential therapeutic strategy,” said Dr. Krysko.

If validated, telomere length may be a biomarker that neurologists could use to guide decisions about MS treatment, said principal investigator Jennifer Graves, MD, PhD, also of UCSF.

“Factors leading to MS progression are not fully understood,” Dr. Krysko said. “But consistently, older chronological age has been associated with a faster time to disability milestones.” Aging may reduce remyelination capacity and alter immunologic responses. Telomere shortening, a marker of cellular aging, is “the ultimate biological clock.” It has been associated with cardiovascular disease, dementia, and autoimmune diseases, and one study found that patients with primary progressive MS have shorter telomere length, compared with controls.

To assess whether LTL is associated with clinical disability and brain volume in patients with MS, the researchers analyzed data from 516 adults with MS or clinically isolated syndrome in the EPIC cohort study at UCSF. Telomere length was measured on stored baseline DNA samples and expressed as the ratio of telomere to a single-copy gene.

The patients had an average age of 43 years, median disease duration of 6 years, and median Expanded Disability Status Scale (EDSS) score of 1.5; about 70% were women. The average telomere length was 0.97.

jremaly@mdedge.com

SOURCE: Krysko KM et al. ACTRIMS Forum 2019, Abstract 289.

DALLAS – Biologic aging as measured by leukocyte telomere length (LTL) is associated with multiple sclerosis (MS) disability progression independent of chronological age, according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Shorter telomere length is associated with increased MS disability in cross-sectional and longitudinal analyses, said Kristen M. Krysko, MD, clinical fellow in neurology at University of California, San Francisco. The results suggest that biologic aging may contribute to neurologic injury in MS and that “targeting aging-related mechanisms may be a potential therapeutic strategy,” said Dr. Krysko.

If validated, telomere length may be a biomarker that neurologists could use to guide decisions about MS treatment, said principal investigator Jennifer Graves, MD, PhD, also of UCSF.

“Factors leading to MS progression are not fully understood,” Dr. Krysko said. “But consistently, older chronological age has been associated with a faster time to disability milestones.” Aging may reduce remyelination capacity and alter immunologic responses. Telomere shortening, a marker of cellular aging, is “the ultimate biological clock.” It has been associated with cardiovascular disease, dementia, and autoimmune diseases, and one study found that patients with primary progressive MS have shorter telomere length, compared with controls.

To assess whether LTL is associated with clinical disability and brain volume in patients with MS, the researchers analyzed data from 516 adults with MS or clinically isolated syndrome in the EPIC cohort study at UCSF. Telomere length was measured on stored baseline DNA samples and expressed as the ratio of telomere to a single-copy gene.

The patients had an average age of 43 years, median disease duration of 6 years, and median Expanded Disability Status Scale (EDSS) score of 1.5; about 70% were women. The average telomere length was 0.97.

jremaly@mdedge.com

SOURCE: Krysko KM et al. ACTRIMS Forum 2019, Abstract 289.

DALLAS – The theme for ACTRIMS Forum 2019 revolves around precision medicine for patients with multiple sclerosis. In an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, the conference’s cochair, Tanuja Chitnis, MD, explained why this is the right time to take a deep dive into what precision medicine means in MS, for patients and physicians alike.

“We chose the topic of precision medicine for this forum because it’s a really timely issue,” said Dr. Chitnis, noting that there are now over 16 approved treatments for MS, and an increasing recognition that “not every patient has the same disease course.”

“It’s the right time to think about individualized treatment, and not a one-size-fits-all approach,” she said, noting that clinicians and patients stand to benefit from guidance about treatment choices.

“In addition, we are aided by the number of biomarkers that are becoming available,” including quantitative MRI and serum biomarkers. “I think we – as a field – need to understand how to use these in clinical settings in order to guide treatment decisions,” said Dr. Chitnis, professor of neurology at Harvard Medical School, Boston.

Advances in data science are allowing the connection of disparate kinds of data for discovery and hypothesis testing and validation, said Dr. Chitnis, who serves as medical director for the large longitudinal CLIMB study. The study follows about 2,000 patients who have yearly neurologic examinations and brain MRI; serum biomarkers and self-report data are also acquired annually.

“Network science can help in the precision medicine approach to multiple sclerosis, because we have a very clear understanding that MS is a complex disease. It is not one gene; it is not one modality,” she said.

Dr. Chitnis reported that she has received research funding from multiple pharmaceutical companies.
 

koakes@mdedge.com

DALLAS – The theme for ACTRIMS Forum 2019 revolves around precision medicine for patients with multiple sclerosis. In an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, the conference’s cochair, Tanuja Chitnis, MD, explained why this is the right time to take a deep dive into what precision medicine means in MS, for patients and physicians alike.

“We chose the topic of precision medicine for this forum because it’s a really timely issue,” said Dr. Chitnis, noting that there are now over 16 approved treatments for MS, and an increasing recognition that “not every patient has the same disease course.”

“It’s the right time to think about individualized treatment, and not a one-size-fits-all approach,” she said, noting that clinicians and patients stand to benefit from guidance about treatment choices.

“In addition, we are aided by the number of biomarkers that are becoming available,” including quantitative MRI and serum biomarkers. “I think we – as a field – need to understand how to use these in clinical settings in order to guide treatment decisions,” said Dr. Chitnis, professor of neurology at Harvard Medical School, Boston.

Advances in data science are allowing the connection of disparate kinds of data for discovery and hypothesis testing and validation, said Dr. Chitnis, who serves as medical director for the large longitudinal CLIMB study. The study follows about 2,000 patients who have yearly neurologic examinations and brain MRI; serum biomarkers and self-report data are also acquired annually.

“Network science can help in the precision medicine approach to multiple sclerosis, because we have a very clear understanding that MS is a complex disease. It is not one gene; it is not one modality,” she said.

Dr. Chitnis reported that she has received research funding from multiple pharmaceutical companies.
 

koakes@mdedge.com

DALLAS – The theme for ACTRIMS Forum 2019 revolves around precision medicine for patients with multiple sclerosis. In an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, the conference’s cochair, Tanuja Chitnis, MD, explained why this is the right time to take a deep dive into what precision medicine means in MS, for patients and physicians alike.

“We chose the topic of precision medicine for this forum because it’s a really timely issue,” said Dr. Chitnis, noting that there are now over 16 approved treatments for MS, and an increasing recognition that “not every patient has the same disease course.”

“It’s the right time to think about individualized treatment, and not a one-size-fits-all approach,” she said, noting that clinicians and patients stand to benefit from guidance about treatment choices.

“In addition, we are aided by the number of biomarkers that are becoming available,” including quantitative MRI and serum biomarkers. “I think we – as a field – need to understand how to use these in clinical settings in order to guide treatment decisions,” said Dr. Chitnis, professor of neurology at Harvard Medical School, Boston.

Advances in data science are allowing the connection of disparate kinds of data for discovery and hypothesis testing and validation, said Dr. Chitnis, who serves as medical director for the large longitudinal CLIMB study. The study follows about 2,000 patients who have yearly neurologic examinations and brain MRI; serum biomarkers and self-report data are also acquired annually.

“Network science can help in the precision medicine approach to multiple sclerosis, because we have a very clear understanding that MS is a complex disease. It is not one gene; it is not one modality,” she said.

Dr. Chitnis reported that she has received research funding from multiple pharmaceutical companies.
 

koakes@mdedge.com