ICYMI Multiple Sclerosis

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – About a third of patients with multiple sclerosis (MS) switch to a more potent disease-modifying therapy (DMT) within 1 year of disease activity being detected on MRI, according to a study of prescribing practices. The number of T2 lesions on MRI may be associated with the likelihood of switching DMTs, said Ryan Canissario, MD, a neurology resident at University of Rochester (New York) Medical Center, and colleagues.

The researchers had hypothesized that “the majority of patients would undergo a change in DMT in response to MRI activity,” they said. Delays in follow-up or therapy start times may partly explain the relatively low rates of switching during the first few months. “We speculate that other reasons ... include clinician or patient risk tolerance, patient age, prior longstanding stability on existing therapy, recent therapy change prior to MRI, or high baseline DMT potency,” the researchers said. Future studies will try to clarify the findings and assess outcomes related to prescribing practices.

Preventing new lesions on MRI is a primary treatment target in MS. “Following this principle, change in [DMT] should be considered in the setting of MRI evidence of disease activity,” but prescribing practices have not been well characterized, Dr. Canissario and colleagues said.

To identify and characterize patients who underwent a DMT change after the detection of brain MRI disease activity, Dr. Canissario and colleagues analyzed data from more than 1,300 patients in MS PATHS (MS Partners Advancing Technology and Health Solutions), a research network of 10 health care institutions. The investigators presented their results at ACTRIMS Forum 2020, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

By consensus, the investigators classified DMTs as low potency (for example, interferons, immunoglobulin G, glatiramer acetate, and teriflunomide), medium potency (azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, methotrexate, and mycophenolate mofetil), or high potency (alemtuzumab, cyclophosphamide, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and rituximab).

The researchers reviewed available imaging data from Apr. 2015 to Aug. 2019 to identify patients with new T2 or gadolinium-enhancing lesions. They determined whether these patients had an escalation in DMT potency or a lateral switch at 3, 6, 9, and 12 months after a radiologist reviewed the MRI.

The number of patients with MRI evidence of disease activity and complete DMT data ranged from 1,364 at 3 months to 952 at 12 months. The proportion of patients who had an escalation in therapy was 17.4% at 3 months, 25.5% at 6 months, 30.4% at 9 months, and 34.3% at 12 months. The proportion with a lateral change was 2% at 3 months, 3.4% at 6 months, 4.3% at 9 months, and 6% at 12 months.

The percentage of patients with DMT escalation or lateral change at 9 months increased with an increasing number of new T2 lesions. About 27% of patients with one new lesion switched therapy, compared with 43.5% of those with more than three new lesions.

Dr. Canissario had no disclosures. Coauthors disclosed research support from and consulting for pharmaceutical companies. MS PATHS is funded by Biogen.

[email protected]

SOURCE: Canissario R et al. ACTRIMS Forum 2020. Abstract P112.

WEST PALM BEACH, FLA. – About a third of patients with multiple sclerosis (MS) switch to a more potent disease-modifying therapy (DMT) within 1 year of disease activity being detected on MRI, according to a study of prescribing practices. The number of T2 lesions on MRI may be associated with the likelihood of switching DMTs, said Ryan Canissario, MD, a neurology resident at University of Rochester (New York) Medical Center, and colleagues.

The researchers had hypothesized that “the majority of patients would undergo a change in DMT in response to MRI activity,” they said. Delays in follow-up or therapy start times may partly explain the relatively low rates of switching during the first few months. “We speculate that other reasons ... include clinician or patient risk tolerance, patient age, prior longstanding stability on existing therapy, recent therapy change prior to MRI, or high baseline DMT potency,” the researchers said. Future studies will try to clarify the findings and assess outcomes related to prescribing practices.

Preventing new lesions on MRI is a primary treatment target in MS. “Following this principle, change in [DMT] should be considered in the setting of MRI evidence of disease activity,” but prescribing practices have not been well characterized, Dr. Canissario and colleagues said.

To identify and characterize patients who underwent a DMT change after the detection of brain MRI disease activity, Dr. Canissario and colleagues analyzed data from more than 1,300 patients in MS PATHS (MS Partners Advancing Technology and Health Solutions), a research network of 10 health care institutions. The investigators presented their results at ACTRIMS Forum 2020, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

By consensus, the investigators classified DMTs as low potency (for example, interferons, immunoglobulin G, glatiramer acetate, and teriflunomide), medium potency (azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, methotrexate, and mycophenolate mofetil), or high potency (alemtuzumab, cyclophosphamide, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and rituximab).

The researchers reviewed available imaging data from Apr. 2015 to Aug. 2019 to identify patients with new T2 or gadolinium-enhancing lesions. They determined whether these patients had an escalation in DMT potency or a lateral switch at 3, 6, 9, and 12 months after a radiologist reviewed the MRI.

The number of patients with MRI evidence of disease activity and complete DMT data ranged from 1,364 at 3 months to 952 at 12 months. The proportion of patients who had an escalation in therapy was 17.4% at 3 months, 25.5% at 6 months, 30.4% at 9 months, and 34.3% at 12 months. The proportion with a lateral change was 2% at 3 months, 3.4% at 6 months, 4.3% at 9 months, and 6% at 12 months.

The percentage of patients with DMT escalation or lateral change at 9 months increased with an increasing number of new T2 lesions. About 27% of patients with one new lesion switched therapy, compared with 43.5% of those with more than three new lesions.

Dr. Canissario had no disclosures. Coauthors disclosed research support from and consulting for pharmaceutical companies. MS PATHS is funded by Biogen.

[email protected]

SOURCE: Canissario R et al. ACTRIMS Forum 2020. Abstract P112.

WEST PALM BEACH, FLA. – About a third of patients with multiple sclerosis (MS) switch to a more potent disease-modifying therapy (DMT) within 1 year of disease activity being detected on MRI, according to a study of prescribing practices. The number of T2 lesions on MRI may be associated with the likelihood of switching DMTs, said Ryan Canissario, MD, a neurology resident at University of Rochester (New York) Medical Center, and colleagues.

The researchers had hypothesized that “the majority of patients would undergo a change in DMT in response to MRI activity,” they said. Delays in follow-up or therapy start times may partly explain the relatively low rates of switching during the first few months. “We speculate that other reasons ... include clinician or patient risk tolerance, patient age, prior longstanding stability on existing therapy, recent therapy change prior to MRI, or high baseline DMT potency,” the researchers said. Future studies will try to clarify the findings and assess outcomes related to prescribing practices.

Preventing new lesions on MRI is a primary treatment target in MS. “Following this principle, change in [DMT] should be considered in the setting of MRI evidence of disease activity,” but prescribing practices have not been well characterized, Dr. Canissario and colleagues said.

To identify and characterize patients who underwent a DMT change after the detection of brain MRI disease activity, Dr. Canissario and colleagues analyzed data from more than 1,300 patients in MS PATHS (MS Partners Advancing Technology and Health Solutions), a research network of 10 health care institutions. The investigators presented their results at ACTRIMS Forum 2020, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

By consensus, the investigators classified DMTs as low potency (for example, interferons, immunoglobulin G, glatiramer acetate, and teriflunomide), medium potency (azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, methotrexate, and mycophenolate mofetil), or high potency (alemtuzumab, cyclophosphamide, mitoxantrone, natalizumab, ocrelizumab, ofatumumab, and rituximab).

The researchers reviewed available imaging data from Apr. 2015 to Aug. 2019 to identify patients with new T2 or gadolinium-enhancing lesions. They determined whether these patients had an escalation in DMT potency or a lateral switch at 3, 6, 9, and 12 months after a radiologist reviewed the MRI.

The number of patients with MRI evidence of disease activity and complete DMT data ranged from 1,364 at 3 months to 952 at 12 months. The proportion of patients who had an escalation in therapy was 17.4% at 3 months, 25.5% at 6 months, 30.4% at 9 months, and 34.3% at 12 months. The proportion with a lateral change was 2% at 3 months, 3.4% at 6 months, 4.3% at 9 months, and 6% at 12 months.

The percentage of patients with DMT escalation or lateral change at 9 months increased with an increasing number of new T2 lesions. About 27% of patients with one new lesion switched therapy, compared with 43.5% of those with more than three new lesions.

Dr. Canissario had no disclosures. Coauthors disclosed research support from and consulting for pharmaceutical companies. MS PATHS is funded by Biogen.

[email protected]

SOURCE: Canissario R et al. ACTRIMS Forum 2020. Abstract P112.

WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.

Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.

The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.

A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.

Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.

The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.

The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.

The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).

“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).

The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.

[email protected]

SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.

WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.

Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.

The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.

A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.

Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.

The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.

The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.

The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).

“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).

The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.

[email protected]

SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.

WEST PALM BEACH, FLA. – The incidence rate of many cardiovascular events is more than doubled in patients with multiple sclerosis (MS), compared with matched controls without MS, according to a study presented at ACTRIMS Forum 2020. The risk of a major adverse cardiac event (MACE) – that is, a first myocardial infarction, stroke, or cardiac arrest – is approximately twofold higher. Venous thromboembolism and peripheral vascular disease also occur at notably increased rates, reported Rebecca Persson, MPH, and colleagues at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. Ms. Persson is an epidemiologist at the Boston Collaborative Drug Surveillance Program in Lexington, Mass.

Vascular comorbidities are more prevalent in patients with MS than in the general population, but few studies have reported on the incidence of cardiovascular disease after MS diagnosis. To describe rates of incident cardiovascular disease after MS diagnosis and compare them with rates in a matched population without MS, the researchers analyzed data from a U.S. Department of Defense database.

The study included a cohort of 6,406 patients with MS diagnosed and treated during Jan. 2004–Aug. 2017 who had at least one prescription for an MS disease-modifying treatment.

A cohort of 66,281 patients without MS were matched to the patients with MS 10:1 based on age, sex, geographic region, and cohort entry date. The researchers excluded patients with a history of cardiovascular disease or select comorbidities such as dyslipidemia, atrial fibrillation, or a disorder related to peripheral vascular disease. They also excluded patients with a history of treated hypertension or treated type 2 diabetes, defined as diagnosis and treatment within 90 days of each other.

Researchers considered a patient to have a cardiovascular disease outcome – including MI, stroke, cardiac arrest, heart failure, angina or unspecified ischemic heart disease, transient ischemic attack or unspecified cerebrovascular disease, venous thromboembolism, peripheral vascular disease, pericardial disease, bradycardia or heart block, or arrhythmia other than atrial fibrillation or atrial flutter – if the disease was recorded five or more times.

The researchers followed patients from cohort entry until study outcome (separate for each outcome), loss of eligibility, death, or end of data collection. Ms. Persson and colleagues calculated incidence rates (IRs) using the Byar method and incidence rate ratios (IRRs) using Poisson regression for each outcome.

The median age at MS diagnosis or at the matched date was 38 years, and 71% were female. The median duration of record after patients entered the cohort was 7.2 years for patients with MS and 5.3 years for patients without MS.

The IRs of all cardiovascular disease types, with the exception of bradycardia or heart block, were higher for patients with MS, compared with non-MS patients, the researchers reported. Many cardiovascular disease outcomes had IRRs greater than 2. “The incidence of MI was higher among MS patients than among non-MS patients,” the researchers said (IR, 12.4 vs. 5.9 per 10,000 person-years; IRR, 2.11).

“Risk of MACE and risk of stroke were higher among MS patients than among non-MS patients,” the researchers said. Relative risks also were higher among women than among men (2.47 vs. 1.55 for MACE, and 2.19 vs. 1.71 for stroke). When the investigators performed a sensitivity analysis to address the possibility that physicians might misdiagnosis MS symptoms as stroke, the rate of stroke was attenuated among patients with MS, but remained elevated relative to the rate among patients without MS (IRR, 1.63).

The IR of venous thromboembolism was more than 2 times higher among patients with MS than among non-MS patients (38.4 vs. 15.1 per 10,000 person-years; IRR, 2.54), as was the risk of peripheral vascular disease (14.9 vs. 6.0 per 10,000 person-years; IRR, 2.49). The relative risk of peripheral vascular disease was higher in women than men, and the risk in patients with MS increased after age 40 years.

The study was funded by a grant from Celgene, a subsidiary of Bristol-Myers Squibb. Four of Ms. Persson’s coauthors are employees of BMS, and one works for a company that has a business relationship with Celgene.

[email protected]

SOURCE: Persson R et al. ACTRIMS Forum 2020. Abstract P082.

WEST PALM BEACH, FLA. – A machine learning model that combines data on the brain’s functional connectivity with clinical information such as age, sex and disease duration shows the potential to provide an accurate assessment of clinical impairment in patients with multiple sclerosis (MS).

“This is the first study to show that dynamic functional connectivity is useful to identify the impairment level in MS, and can be used for personalized treatment by clinicians,” first author Ceren Tozlu, PhD, of Weill Cornell Medicine, New York, said in an interview.

“We found out that structural connectivity is the most important feature that distinguishes MS patients from healthy controls, while dynamic functional connectivity was more discriminative compared to the static functional connectivity in MS patient classification regarding their impairment level.”

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Statistical assessment of the clinical impairment of MS using MRI is hindered by a relatively weak correlation between the impairment and disease burden, such as lesion load.

However, the brain’s functional connectivity network, which is indicative of the disruption of the transmission of signals of gray matter regions, could provide a deeper understanding of connectome-level mechanisms that underlie variability in MS-related impairments, Dr. Tozlu and colleagues say.

With no previous study pulling together multimodal imaging data including static and dynamic functional connectivity to classify MS patients with a clinically significant impairment versus non–clinically significant impairment, Dr. Tozlu and the team sought to build a machine-learning–based model to do so.

For the study, they enrolled 79 patients with MS, including 42 with Expanded Disability Status scores of 2 or higher, representing clinically significant impairment at baseline.

The patients, who had a mean age of 45 years, were 66% female and had a mean disease duration of 12.48 years. The ensemble model that was used incorporated functional connectivity and a clinical dataset of age, sex, and disease duration. Functional connectivity was measured by evaluating blood oxygen level dependent (BOLD) signal activity between 86 FreeSurfer-based gray matter regions.

“Functional connectivity is a statistical correlation (Pearson’s correlation coefficient) between two time series of BOLD signals measured on two distinct region of interest of the brain during MRI scan,” Dr. Tozlu explained. “In our study, BOLD time series were measured using resting-state functional MRI technique that last 7 minutes.”

The ensemble model was able to classify low-adapting MS patients with an area under ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659. The model performed well in accurately classifying the MS patients with clinically significant impairment with a sensitivity of 0.719.

“The models in which we applied functional and structural connectivity showed a high performance in classifying MS patients regarding their impairment level,” Dr. Tozlu said.

She noted that “these models may be extended to predict change in impairment level in a longitudinal study, for instance, identifying MS patients who may have a clinically significant impairment.”

In further evaluating which particular functional connections were most related to MS disease activity, Dr. Tozlu and colleagues found the most discriminative areas were between the right superior parietal and right inferior temporal, between right lateral occipital and left pericalcarine, and between right pericalcarine and right side of frontal pole.

If further validated, the approach could have important, broader clinical implications, Dr. Tozlu said.

“If the validation of these models on a larger dataset is successful, this model may be used to decide for personalized treatment,” Dr. Tozlu added. “The model could offer guidance in providing more powerful treatment for MS patients who may have a clinically significant impairment and less powerful treatment for MS patients who may not have a clinically significant impairment in order to avoid the side effects of treatments.

“Therefore, we believe that dynamics in functional connectivity should be taken into account in the next studies in MS.”

In commenting on the research, Eric Klawiter, MD, associate professor of neurology, Harvard Medical School and associate neurologist at Massachusetts General Hospital, both in Boston, said the findings offer valuable insights in the use of machine learning and MS imaging.

“This research shows very nicely the power of machine learning and connectivity techniques to differentiate MS phenotypes based on disability level,” he said in an interview.

“The future direction of this work is to develop predictive markers for disability progression and this would have significant impact in how we evaluate newly diagnosed patients and counsel their treatment decisions.”

Dr. Tozlu and Dr. Klawiter had no disclosures to report.

SOURCE: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.

WEST PALM BEACH, FLA. – A machine learning model that combines data on the brain’s functional connectivity with clinical information such as age, sex and disease duration shows the potential to provide an accurate assessment of clinical impairment in patients with multiple sclerosis (MS).

“This is the first study to show that dynamic functional connectivity is useful to identify the impairment level in MS, and can be used for personalized treatment by clinicians,” first author Ceren Tozlu, PhD, of Weill Cornell Medicine, New York, said in an interview.

“We found out that structural connectivity is the most important feature that distinguishes MS patients from healthy controls, while dynamic functional connectivity was more discriminative compared to the static functional connectivity in MS patient classification regarding their impairment level.”

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Statistical assessment of the clinical impairment of MS using MRI is hindered by a relatively weak correlation between the impairment and disease burden, such as lesion load.

However, the brain’s functional connectivity network, which is indicative of the disruption of the transmission of signals of gray matter regions, could provide a deeper understanding of connectome-level mechanisms that underlie variability in MS-related impairments, Dr. Tozlu and colleagues say.

With no previous study pulling together multimodal imaging data including static and dynamic functional connectivity to classify MS patients with a clinically significant impairment versus non–clinically significant impairment, Dr. Tozlu and the team sought to build a machine-learning–based model to do so.

For the study, they enrolled 79 patients with MS, including 42 with Expanded Disability Status scores of 2 or higher, representing clinically significant impairment at baseline.

The patients, who had a mean age of 45 years, were 66% female and had a mean disease duration of 12.48 years. The ensemble model that was used incorporated functional connectivity and a clinical dataset of age, sex, and disease duration. Functional connectivity was measured by evaluating blood oxygen level dependent (BOLD) signal activity between 86 FreeSurfer-based gray matter regions.

“Functional connectivity is a statistical correlation (Pearson’s correlation coefficient) between two time series of BOLD signals measured on two distinct region of interest of the brain during MRI scan,” Dr. Tozlu explained. “In our study, BOLD time series were measured using resting-state functional MRI technique that last 7 minutes.”

The ensemble model was able to classify low-adapting MS patients with an area under ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659. The model performed well in accurately classifying the MS patients with clinically significant impairment with a sensitivity of 0.719.

“The models in which we applied functional and structural connectivity showed a high performance in classifying MS patients regarding their impairment level,” Dr. Tozlu said.

She noted that “these models may be extended to predict change in impairment level in a longitudinal study, for instance, identifying MS patients who may have a clinically significant impairment.”

In further evaluating which particular functional connections were most related to MS disease activity, Dr. Tozlu and colleagues found the most discriminative areas were between the right superior parietal and right inferior temporal, between right lateral occipital and left pericalcarine, and between right pericalcarine and right side of frontal pole.

If further validated, the approach could have important, broader clinical implications, Dr. Tozlu said.

“If the validation of these models on a larger dataset is successful, this model may be used to decide for personalized treatment,” Dr. Tozlu added. “The model could offer guidance in providing more powerful treatment for MS patients who may have a clinically significant impairment and less powerful treatment for MS patients who may not have a clinically significant impairment in order to avoid the side effects of treatments.

“Therefore, we believe that dynamics in functional connectivity should be taken into account in the next studies in MS.”

In commenting on the research, Eric Klawiter, MD, associate professor of neurology, Harvard Medical School and associate neurologist at Massachusetts General Hospital, both in Boston, said the findings offer valuable insights in the use of machine learning and MS imaging.

“This research shows very nicely the power of machine learning and connectivity techniques to differentiate MS phenotypes based on disability level,” he said in an interview.

“The future direction of this work is to develop predictive markers for disability progression and this would have significant impact in how we evaluate newly diagnosed patients and counsel their treatment decisions.”

Dr. Tozlu and Dr. Klawiter had no disclosures to report.

SOURCE: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.

WEST PALM BEACH, FLA. – A machine learning model that combines data on the brain’s functional connectivity with clinical information such as age, sex and disease duration shows the potential to provide an accurate assessment of clinical impairment in patients with multiple sclerosis (MS).

“This is the first study to show that dynamic functional connectivity is useful to identify the impairment level in MS, and can be used for personalized treatment by clinicians,” first author Ceren Tozlu, PhD, of Weill Cornell Medicine, New York, said in an interview.

“We found out that structural connectivity is the most important feature that distinguishes MS patients from healthy controls, while dynamic functional connectivity was more discriminative compared to the static functional connectivity in MS patient classification regarding their impairment level.”

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Statistical assessment of the clinical impairment of MS using MRI is hindered by a relatively weak correlation between the impairment and disease burden, such as lesion load.

However, the brain’s functional connectivity network, which is indicative of the disruption of the transmission of signals of gray matter regions, could provide a deeper understanding of connectome-level mechanisms that underlie variability in MS-related impairments, Dr. Tozlu and colleagues say.

With no previous study pulling together multimodal imaging data including static and dynamic functional connectivity to classify MS patients with a clinically significant impairment versus non–clinically significant impairment, Dr. Tozlu and the team sought to build a machine-learning–based model to do so.

For the study, they enrolled 79 patients with MS, including 42 with Expanded Disability Status scores of 2 or higher, representing clinically significant impairment at baseline.

The patients, who had a mean age of 45 years, were 66% female and had a mean disease duration of 12.48 years. The ensemble model that was used incorporated functional connectivity and a clinical dataset of age, sex, and disease duration. Functional connectivity was measured by evaluating blood oxygen level dependent (BOLD) signal activity between 86 FreeSurfer-based gray matter regions.

“Functional connectivity is a statistical correlation (Pearson’s correlation coefficient) between two time series of BOLD signals measured on two distinct region of interest of the brain during MRI scan,” Dr. Tozlu explained. “In our study, BOLD time series were measured using resting-state functional MRI technique that last 7 minutes.”

The ensemble model was able to classify low-adapting MS patients with an area under ROC curve (AUC) of 0.638 and a balanced accuracy of 0.659. The model performed well in accurately classifying the MS patients with clinically significant impairment with a sensitivity of 0.719.

“The models in which we applied functional and structural connectivity showed a high performance in classifying MS patients regarding their impairment level,” Dr. Tozlu said.

She noted that “these models may be extended to predict change in impairment level in a longitudinal study, for instance, identifying MS patients who may have a clinically significant impairment.”

In further evaluating which particular functional connections were most related to MS disease activity, Dr. Tozlu and colleagues found the most discriminative areas were between the right superior parietal and right inferior temporal, between right lateral occipital and left pericalcarine, and between right pericalcarine and right side of frontal pole.

If further validated, the approach could have important, broader clinical implications, Dr. Tozlu said.

“If the validation of these models on a larger dataset is successful, this model may be used to decide for personalized treatment,” Dr. Tozlu added. “The model could offer guidance in providing more powerful treatment for MS patients who may have a clinically significant impairment and less powerful treatment for MS patients who may not have a clinically significant impairment in order to avoid the side effects of treatments.

“Therefore, we believe that dynamics in functional connectivity should be taken into account in the next studies in MS.”

In commenting on the research, Eric Klawiter, MD, associate professor of neurology, Harvard Medical School and associate neurologist at Massachusetts General Hospital, both in Boston, said the findings offer valuable insights in the use of machine learning and MS imaging.

“This research shows very nicely the power of machine learning and connectivity techniques to differentiate MS phenotypes based on disability level,” he said in an interview.

“The future direction of this work is to develop predictive markers for disability progression and this would have significant impact in how we evaluate newly diagnosed patients and counsel their treatment decisions.”

Dr. Tozlu and Dr. Klawiter had no disclosures to report.

SOURCE: Tozlu C et al. ACTRIMS Forum 2020. Abstract P025.

WEST PALM BEACH, FLA. – Compared with placebo, inebilizumab reduces the risk of attacks, the risk of disability worsening, the number of hospitalizations, and the number of new MRI lesions in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The drug’s efficacy was sustained for one year in the study, and the treatment had an acceptable safety profile.

“Multiple lines of evidence suggest that NMO is predominantly a B-cell–mediated disorder,” said Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences. Inebilizumab depletes B cells and reduces inflammatory disease activity in NMO potentially by altering immune networks that are dependent on B cells for cytokine production or antigen presentation.” Inebilizumab is an anti-CD19 monoclonal antibody.

Dr. Cree and colleagues conducted a randomized, controlled trial called N-MOmentum to characterize the long-term efficacy and safety of inebilizumab in patients with NMOSD. The investigators randomized patients with NMOSD to inebilizumab or placebo monotherapy in a 3:1 ratio for 6.5 months. The study’s primary outcome was the time to the first adjudicated attack. Patients who had an adjudicated attack or completed the trial could receive inebilizumab in an ongoing open-label extension.

The study was conducted at 99 sites in 25 countries. In all, 230 patients were randomized and dosed (174 received inebilizumab, and 56 received placebo). About 91% of the population was aquaporin-4-IgG–positive (AQP4-IgG+), and 91% was female. The population’s mean age at baseline was 43 years. The population’s median baseline Expanded Disability Status Scale score was approximately 3.5, and the range was from 0 to 8.0. Approximately 50% of participants were white, 20% were Asian, and 9% were of African descent. “The demographic profile is similar to that of many published studies,” said Dr. Cree.

Because of clear evidence of efficacy, the independent data monitoring committee recommended that the study be stopped early. In the randomized, controlled trial, inebilizumab reduced the risk of attack by 77.3% among AQP4-IgG+ patients and by 72.8% in the total population. The number needed to treat for 6.5 months to prevent one attack was 3.2 for the AQP4-IgG+ group and 3.7 for the total population.

Furthermore, inebilizumab significantly reduced the risk of worsening disability, the number of new MRI lesions, and NMOSD-related hospitalizations. After 1 year on inebilizumab, 85% of patients were free of an NMOSD attack. In safety analyses that combined data from the randomized, controlled trial and interim data from the open-label extension, the mean duration of inebilizumab treatment was 1.5 years.

“The rapid effect of inebilizumab on attack prevention is not mediated by decreasing AQP4-IgG, although it is possible that long-term inebilizumab treatment might eventually reduce AQP4-IgG production,” said Dr. Cree.

The most common adverse events (AEs) were urinary tract infection (UTI, 19.6%), nasopharyngitis (12.9%), and infusion-related reactions (IRRs, 11.6%). IRRs were most common with the first infusion. The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal was 7.5% at 1 year and 13.4% at 2 years. Serious AEs occurred in 12% of patients, and UTI was the most common (2.2%). Two patients died in the open-label extension; one death resulted from NMOSD, and one from new presumed inflammatory brain lesions of undetermined etiology.

“The open-label results show a striking durability of treatment effect,” said Dr. Cree. “Most of the attacks that occurred during the open-label extension occurred early on, suggesting that the risk of attack decreases with duration of B-cell depletion. The open-label study also is important for assessing the longer-term AE profile of inebilizumab treatment. One potentially important observation from the open-label extension is that the extent of B-cell depletion correlates with reduced attack risk. Approximately 95% of participants with deep B-cell depletion were free of attacks. Participants who either incompletely depleted B cells or who began to reconstitute B cells more rapidly were at increased risk of attack. Therefore, by monitoring B-cell counts in inebilizumab-treated patients, it may be possible to further reduce the risk of attack in patients who partially deplete, or replete B cells early, with an extra inebilizumab treatment.”

Viela Bio, which is developing inebilizumab, and MedImmune sponsored the study. Dr. Cree has received compensation for consulting services that he provided to Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.

[email protected]

SOURCE: Cree BA et al. ACTRIMS 2020. Abstract P207.

WEST PALM BEACH, FLA. – Compared with placebo, inebilizumab reduces the risk of attacks, the risk of disability worsening, the number of hospitalizations, and the number of new MRI lesions in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The drug’s efficacy was sustained for one year in the study, and the treatment had an acceptable safety profile.

“Multiple lines of evidence suggest that NMO is predominantly a B-cell–mediated disorder,” said Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences. Inebilizumab depletes B cells and reduces inflammatory disease activity in NMO potentially by altering immune networks that are dependent on B cells for cytokine production or antigen presentation.” Inebilizumab is an anti-CD19 monoclonal antibody.

Dr. Cree and colleagues conducted a randomized, controlled trial called N-MOmentum to characterize the long-term efficacy and safety of inebilizumab in patients with NMOSD. The investigators randomized patients with NMOSD to inebilizumab or placebo monotherapy in a 3:1 ratio for 6.5 months. The study’s primary outcome was the time to the first adjudicated attack. Patients who had an adjudicated attack or completed the trial could receive inebilizumab in an ongoing open-label extension.

The study was conducted at 99 sites in 25 countries. In all, 230 patients were randomized and dosed (174 received inebilizumab, and 56 received placebo). About 91% of the population was aquaporin-4-IgG–positive (AQP4-IgG+), and 91% was female. The population’s mean age at baseline was 43 years. The population’s median baseline Expanded Disability Status Scale score was approximately 3.5, and the range was from 0 to 8.0. Approximately 50% of participants were white, 20% were Asian, and 9% were of African descent. “The demographic profile is similar to that of many published studies,” said Dr. Cree.

Because of clear evidence of efficacy, the independent data monitoring committee recommended that the study be stopped early. In the randomized, controlled trial, inebilizumab reduced the risk of attack by 77.3% among AQP4-IgG+ patients and by 72.8% in the total population. The number needed to treat for 6.5 months to prevent one attack was 3.2 for the AQP4-IgG+ group and 3.7 for the total population.

Furthermore, inebilizumab significantly reduced the risk of worsening disability, the number of new MRI lesions, and NMOSD-related hospitalizations. After 1 year on inebilizumab, 85% of patients were free of an NMOSD attack. In safety analyses that combined data from the randomized, controlled trial and interim data from the open-label extension, the mean duration of inebilizumab treatment was 1.5 years.

“The rapid effect of inebilizumab on attack prevention is not mediated by decreasing AQP4-IgG, although it is possible that long-term inebilizumab treatment might eventually reduce AQP4-IgG production,” said Dr. Cree.

The most common adverse events (AEs) were urinary tract infection (UTI, 19.6%), nasopharyngitis (12.9%), and infusion-related reactions (IRRs, 11.6%). IRRs were most common with the first infusion. The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal was 7.5% at 1 year and 13.4% at 2 years. Serious AEs occurred in 12% of patients, and UTI was the most common (2.2%). Two patients died in the open-label extension; one death resulted from NMOSD, and one from new presumed inflammatory brain lesions of undetermined etiology.

“The open-label results show a striking durability of treatment effect,” said Dr. Cree. “Most of the attacks that occurred during the open-label extension occurred early on, suggesting that the risk of attack decreases with duration of B-cell depletion. The open-label study also is important for assessing the longer-term AE profile of inebilizumab treatment. One potentially important observation from the open-label extension is that the extent of B-cell depletion correlates with reduced attack risk. Approximately 95% of participants with deep B-cell depletion were free of attacks. Participants who either incompletely depleted B cells or who began to reconstitute B cells more rapidly were at increased risk of attack. Therefore, by monitoring B-cell counts in inebilizumab-treated patients, it may be possible to further reduce the risk of attack in patients who partially deplete, or replete B cells early, with an extra inebilizumab treatment.”

Viela Bio, which is developing inebilizumab, and MedImmune sponsored the study. Dr. Cree has received compensation for consulting services that he provided to Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.

[email protected]

SOURCE: Cree BA et al. ACTRIMS 2020. Abstract P207.

WEST PALM BEACH, FLA. – Compared with placebo, inebilizumab reduces the risk of attacks, the risk of disability worsening, the number of hospitalizations, and the number of new MRI lesions in patients with neuromyelitis optica spectrum disorder (NMOSD), according to a study presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The drug’s efficacy was sustained for one year in the study, and the treatment had an acceptable safety profile.

“Multiple lines of evidence suggest that NMO is predominantly a B-cell–mediated disorder,” said Bruce Cree, MD, PhD, professor of neurology at the University of California, San Francisco, Weill Institute for Neurosciences. Inebilizumab depletes B cells and reduces inflammatory disease activity in NMO potentially by altering immune networks that are dependent on B cells for cytokine production or antigen presentation.” Inebilizumab is an anti-CD19 monoclonal antibody.

Dr. Cree and colleagues conducted a randomized, controlled trial called N-MOmentum to characterize the long-term efficacy and safety of inebilizumab in patients with NMOSD. The investigators randomized patients with NMOSD to inebilizumab or placebo monotherapy in a 3:1 ratio for 6.5 months. The study’s primary outcome was the time to the first adjudicated attack. Patients who had an adjudicated attack or completed the trial could receive inebilizumab in an ongoing open-label extension.

The study was conducted at 99 sites in 25 countries. In all, 230 patients were randomized and dosed (174 received inebilizumab, and 56 received placebo). About 91% of the population was aquaporin-4-IgG–positive (AQP4-IgG+), and 91% was female. The population’s mean age at baseline was 43 years. The population’s median baseline Expanded Disability Status Scale score was approximately 3.5, and the range was from 0 to 8.0. Approximately 50% of participants were white, 20% were Asian, and 9% were of African descent. “The demographic profile is similar to that of many published studies,” said Dr. Cree.

Because of clear evidence of efficacy, the independent data monitoring committee recommended that the study be stopped early. In the randomized, controlled trial, inebilizumab reduced the risk of attack by 77.3% among AQP4-IgG+ patients and by 72.8% in the total population. The number needed to treat for 6.5 months to prevent one attack was 3.2 for the AQP4-IgG+ group and 3.7 for the total population.

Furthermore, inebilizumab significantly reduced the risk of worsening disability, the number of new MRI lesions, and NMOSD-related hospitalizations. After 1 year on inebilizumab, 85% of patients were free of an NMOSD attack. In safety analyses that combined data from the randomized, controlled trial and interim data from the open-label extension, the mean duration of inebilizumab treatment was 1.5 years.

“The rapid effect of inebilizumab on attack prevention is not mediated by decreasing AQP4-IgG, although it is possible that long-term inebilizumab treatment might eventually reduce AQP4-IgG production,” said Dr. Cree.

The most common adverse events (AEs) were urinary tract infection (UTI, 19.6%), nasopharyngitis (12.9%), and infusion-related reactions (IRRs, 11.6%). IRRs were most common with the first infusion. The proportion of inebilizumab-treated patients with IgG levels below the lower limit of normal was 7.5% at 1 year and 13.4% at 2 years. Serious AEs occurred in 12% of patients, and UTI was the most common (2.2%). Two patients died in the open-label extension; one death resulted from NMOSD, and one from new presumed inflammatory brain lesions of undetermined etiology.

“The open-label results show a striking durability of treatment effect,” said Dr. Cree. “Most of the attacks that occurred during the open-label extension occurred early on, suggesting that the risk of attack decreases with duration of B-cell depletion. The open-label study also is important for assessing the longer-term AE profile of inebilizumab treatment. One potentially important observation from the open-label extension is that the extent of B-cell depletion correlates with reduced attack risk. Approximately 95% of participants with deep B-cell depletion were free of attacks. Participants who either incompletely depleted B cells or who began to reconstitute B cells more rapidly were at increased risk of attack. Therefore, by monitoring B-cell counts in inebilizumab-treated patients, it may be possible to further reduce the risk of attack in patients who partially deplete, or replete B cells early, with an extra inebilizumab treatment.”

Viela Bio, which is developing inebilizumab, and MedImmune sponsored the study. Dr. Cree has received compensation for consulting services that he provided to Alexion, Atara, Biogen, EMD Serono, Novartis, and TG Therapeutics.

[email protected]

SOURCE: Cree BA et al. ACTRIMS 2020. Abstract P207.

WEST PALM BEACH, FLA. – Compared with placebo, eculizumab reduces the number of relapse-related hospitalizations and their associated treatment rates in patients with aquaporin-4 immunoglobulin-G (AQP4-IgG)–positive neuromyelitis optica spectrum disorder (NMOSD), according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that eculizumab may have a favorable effect on health-resource utilization.

Many patients with NMOSD, a rare autoimmune inflammatory disease, have relapses that result in hospitalization. Eculizumab (Soliris)is a humanized monoclonal antibody that inhibits the terminal complement protein C5. In the randomized, double-blind, placebo-controlled PREVENT study, Dean M. Wingerchuk, MD, chair of neurology at Mayo Clinic in Phoenix, , and colleagues found that eculizumab was associated with a 94% reduction in the risk of relapse, compared with placebo, in AQP4-IgG-positive patients with NMOSD.

In a new analysis of the PREVENT data, the investigators sought to evaluate rates of relapse-related hospitalization and associated treatment among study participants. The researchers chose time to first adjudicated relapse as their primary endpoint.

In the PREVENT study, Dr. Wingerchuk and colleagues randomized patients with AQP4-IgG-positive NMOSD to eculizumab (1,200 mg/2 weeks) or placebo. The annualized relapse-related hospitalization and treatment rates were calculated as the number of relapses requiring hospitalization or treatment divided by the total number of patient-years during the study.

Approximately 91% of participants were female. Mean age at initial clinical presentation was about 37 years. Participants’ median Expanded Disability Status Scale score at baseline was 4, and their mean annualized relapse rate in the 24 months before screening was 2. In all, 96 patients received eculizumab, and 47 received placebo. The median length of exposure to treatment was 89.4 weeks in the eculizumab group and 41.3 weeks among controls.

The rate of adverse events requiring hospitalization was 29% in the eculizumab group and 53% in the placebo group. The most common events requiring hospitalization were physician-determined relapses. Infections were the next most common events requiring hospitalization.

The overall annualized hospitalization rate was 0.26 in the eculizumab group and 0.78 in the placebo group. The difference between groups was statistically significant. In addition, the annualized relapse-related hospitalization rate was lower in the eculizumab group than in the placebo group (0.04 vs. 0.31, respectively).

The annualized relapse-related use of intravenous methylprednisolone for the eculizumab and placebo groups were 0.07 and 0.42, respectively; for use of plasma exchange, 0.02 and 0.19; and for use of high-dose oral corticosteroids, 0.04 and 0.11. The differences between groups in use of intravenous methylprednisolone and plasma exchange were statistically significant.

Alexion Pharmaceuticals, which markets eculizumab, sponsored the study. Dr. Wingerchuk received grants from Alexion during the study. He also received personal fees from Biogen, BrainStorm Therapeutics, Celgene, MedImmune, Novartis, and ONO Pharmaceutical.

[email protected]

SOURCE: Kim H et al. ACTRIMS 2020. Abstract P197.

WEST PALM BEACH, FLA. – Compared with placebo, eculizumab reduces the number of relapse-related hospitalizations and their associated treatment rates in patients with aquaporin-4 immunoglobulin-G (AQP4-IgG)–positive neuromyelitis optica spectrum disorder (NMOSD), according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that eculizumab may have a favorable effect on health-resource utilization.

Many patients with NMOSD, a rare autoimmune inflammatory disease, have relapses that result in hospitalization. Eculizumab (Soliris)is a humanized monoclonal antibody that inhibits the terminal complement protein C5. In the randomized, double-blind, placebo-controlled PREVENT study, Dean M. Wingerchuk, MD, chair of neurology at Mayo Clinic in Phoenix, , and colleagues found that eculizumab was associated with a 94% reduction in the risk of relapse, compared with placebo, in AQP4-IgG-positive patients with NMOSD.

In a new analysis of the PREVENT data, the investigators sought to evaluate rates of relapse-related hospitalization and associated treatment among study participants. The researchers chose time to first adjudicated relapse as their primary endpoint.

In the PREVENT study, Dr. Wingerchuk and colleagues randomized patients with AQP4-IgG-positive NMOSD to eculizumab (1,200 mg/2 weeks) or placebo. The annualized relapse-related hospitalization and treatment rates were calculated as the number of relapses requiring hospitalization or treatment divided by the total number of patient-years during the study.

Approximately 91% of participants were female. Mean age at initial clinical presentation was about 37 years. Participants’ median Expanded Disability Status Scale score at baseline was 4, and their mean annualized relapse rate in the 24 months before screening was 2. In all, 96 patients received eculizumab, and 47 received placebo. The median length of exposure to treatment was 89.4 weeks in the eculizumab group and 41.3 weeks among controls.

The rate of adverse events requiring hospitalization was 29% in the eculizumab group and 53% in the placebo group. The most common events requiring hospitalization were physician-determined relapses. Infections were the next most common events requiring hospitalization.

The overall annualized hospitalization rate was 0.26 in the eculizumab group and 0.78 in the placebo group. The difference between groups was statistically significant. In addition, the annualized relapse-related hospitalization rate was lower in the eculizumab group than in the placebo group (0.04 vs. 0.31, respectively).

The annualized relapse-related use of intravenous methylprednisolone for the eculizumab and placebo groups were 0.07 and 0.42, respectively; for use of plasma exchange, 0.02 and 0.19; and for use of high-dose oral corticosteroids, 0.04 and 0.11. The differences between groups in use of intravenous methylprednisolone and plasma exchange were statistically significant.

Alexion Pharmaceuticals, which markets eculizumab, sponsored the study. Dr. Wingerchuk received grants from Alexion during the study. He also received personal fees from Biogen, BrainStorm Therapeutics, Celgene, MedImmune, Novartis, and ONO Pharmaceutical.

[email protected]

SOURCE: Kim H et al. ACTRIMS 2020. Abstract P197.

WEST PALM BEACH, FLA. – Compared with placebo, eculizumab reduces the number of relapse-related hospitalizations and their associated treatment rates in patients with aquaporin-4 immunoglobulin-G (AQP4-IgG)–positive neuromyelitis optica spectrum disorder (NMOSD), according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. The results suggest that eculizumab may have a favorable effect on health-resource utilization.

Many patients with NMOSD, a rare autoimmune inflammatory disease, have relapses that result in hospitalization. Eculizumab (Soliris)is a humanized monoclonal antibody that inhibits the terminal complement protein C5. In the randomized, double-blind, placebo-controlled PREVENT study, Dean M. Wingerchuk, MD, chair of neurology at Mayo Clinic in Phoenix, , and colleagues found that eculizumab was associated with a 94% reduction in the risk of relapse, compared with placebo, in AQP4-IgG-positive patients with NMOSD.

In a new analysis of the PREVENT data, the investigators sought to evaluate rates of relapse-related hospitalization and associated treatment among study participants. The researchers chose time to first adjudicated relapse as their primary endpoint.

In the PREVENT study, Dr. Wingerchuk and colleagues randomized patients with AQP4-IgG-positive NMOSD to eculizumab (1,200 mg/2 weeks) or placebo. The annualized relapse-related hospitalization and treatment rates were calculated as the number of relapses requiring hospitalization or treatment divided by the total number of patient-years during the study.

Approximately 91% of participants were female. Mean age at initial clinical presentation was about 37 years. Participants’ median Expanded Disability Status Scale score at baseline was 4, and their mean annualized relapse rate in the 24 months before screening was 2. In all, 96 patients received eculizumab, and 47 received placebo. The median length of exposure to treatment was 89.4 weeks in the eculizumab group and 41.3 weeks among controls.

The rate of adverse events requiring hospitalization was 29% in the eculizumab group and 53% in the placebo group. The most common events requiring hospitalization were physician-determined relapses. Infections were the next most common events requiring hospitalization.

The overall annualized hospitalization rate was 0.26 in the eculizumab group and 0.78 in the placebo group. The difference between groups was statistically significant. In addition, the annualized relapse-related hospitalization rate was lower in the eculizumab group than in the placebo group (0.04 vs. 0.31, respectively).

The annualized relapse-related use of intravenous methylprednisolone for the eculizumab and placebo groups were 0.07 and 0.42, respectively; for use of plasma exchange, 0.02 and 0.19; and for use of high-dose oral corticosteroids, 0.04 and 0.11. The differences between groups in use of intravenous methylprednisolone and plasma exchange were statistically significant.

Alexion Pharmaceuticals, which markets eculizumab, sponsored the study. Dr. Wingerchuk received grants from Alexion during the study. He also received personal fees from Biogen, BrainStorm Therapeutics, Celgene, MedImmune, Novartis, and ONO Pharmaceutical.

[email protected]

SOURCE: Kim H et al. ACTRIMS 2020. Abstract P197.

WEST PALM BEACH, FLA. – Serum neurofilament light (NfL) levels measured during the first several years after the clinical onset of multiple sclerosis (MS) may predict deep gray matter volumes at 10 years, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Researchers have begun to study longitudinal changes in serum NfL levels as a way to monitor axonal damage in patients with MS and see how they relate to other measures of neuronal loss, such as brain atrophy, and clinical outcomes over the long-term. “Deep gray matter volumes have been shown to correlate with neurological outcomes in MS patients. In particular, thalamic volume has been shown to correlate with measures of cognitive processing speed, such as the Symbol Digit Modalities Test,” said senior author Tanuja Chitnis, MD, professor of neurology at Harvard Medical School in Boston.

She and her colleagues sought to determine whether annual serum NfL measures could predict 10-year deep gray matter atrophy measured by volumetric MRI in patients with MS. They examined patients who were enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Eligible participants were enrolled within 5 years of disease onset and had had annual blood samples drawn for as long as 10 years. In all, 122 patients met these criteria. The investigators measured serum NfL and compared it against deep gray matter volume in the thalamus, caudate, putamen, and globus pallidus from high-resolution 3-T MRI scans taken at year 10. Dr. Chitnis and colleagues assessed correlations between averaged annual NfL and 10-year MRI outcomes using univariate and multivariate linear regression models.

About 96% of participants were white, and about 2% were black. Approximately 73% of participants were female. Average age at the first symptom was 36 years, and average age at the first sample collection was 38 years.

The investigators found several negative associations between averaged NfL values and various MRI volumetric outcomes. Averaged annual serum NfL levels for the first 5 years were significantly and negatively associated with 10-year thalamic volumes in the unadjusted analysis. A 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000272 cm³ in thalamic volume. The association remained significant in an analysis adjusted for age, sex, and disease duration. In this analysis, a 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000259 cm³ in thalamic volume. Analyzing serum NfL levels beyond year 5 did not reveal a stronger association. Serum NfL levels during the first 5 years accounted for about 24% of the variance in 10-year thalamic volumes. Dr. Chitnis and colleagues found similar statistically significant associations between serum NfL levels and caudate, putamen, and globus pallidus volumes. “Therefore, early serum NfL levels contribute to the identification of patients who may require highly effective therapies,” she said.

“We will continue to validate these results. As well, we are exploring other early biomarkers that increase predictive power of long-term outcomes in MS, with the goal of identifying patients most appropriate for high-efficacy treatments.”

The study was supported by funds from the U.S. Department of Defense, Novartis, and the Swiss National Research Foundation. Dr. Chitnis has received personal compensation for consulting and advisory board membership from Biogen, Merck Serono, Novartis, and Sanofi.

[email protected]

SOURCE: Lokhande H et al. ACTRIMS Forum 2020, Abstract P018.

WEST PALM BEACH, FLA. – Serum neurofilament light (NfL) levels measured during the first several years after the clinical onset of multiple sclerosis (MS) may predict deep gray matter volumes at 10 years, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Researchers have begun to study longitudinal changes in serum NfL levels as a way to monitor axonal damage in patients with MS and see how they relate to other measures of neuronal loss, such as brain atrophy, and clinical outcomes over the long-term. “Deep gray matter volumes have been shown to correlate with neurological outcomes in MS patients. In particular, thalamic volume has been shown to correlate with measures of cognitive processing speed, such as the Symbol Digit Modalities Test,” said senior author Tanuja Chitnis, MD, professor of neurology at Harvard Medical School in Boston.

She and her colleagues sought to determine whether annual serum NfL measures could predict 10-year deep gray matter atrophy measured by volumetric MRI in patients with MS. They examined patients who were enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Eligible participants were enrolled within 5 years of disease onset and had had annual blood samples drawn for as long as 10 years. In all, 122 patients met these criteria. The investigators measured serum NfL and compared it against deep gray matter volume in the thalamus, caudate, putamen, and globus pallidus from high-resolution 3-T MRI scans taken at year 10. Dr. Chitnis and colleagues assessed correlations between averaged annual NfL and 10-year MRI outcomes using univariate and multivariate linear regression models.

About 96% of participants were white, and about 2% were black. Approximately 73% of participants were female. Average age at the first symptom was 36 years, and average age at the first sample collection was 38 years.

The investigators found several negative associations between averaged NfL values and various MRI volumetric outcomes. Averaged annual serum NfL levels for the first 5 years were significantly and negatively associated with 10-year thalamic volumes in the unadjusted analysis. A 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000272 cm³ in thalamic volume. The association remained significant in an analysis adjusted for age, sex, and disease duration. In this analysis, a 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000259 cm³ in thalamic volume. Analyzing serum NfL levels beyond year 5 did not reveal a stronger association. Serum NfL levels during the first 5 years accounted for about 24% of the variance in 10-year thalamic volumes. Dr. Chitnis and colleagues found similar statistically significant associations between serum NfL levels and caudate, putamen, and globus pallidus volumes. “Therefore, early serum NfL levels contribute to the identification of patients who may require highly effective therapies,” she said.

“We will continue to validate these results. As well, we are exploring other early biomarkers that increase predictive power of long-term outcomes in MS, with the goal of identifying patients most appropriate for high-efficacy treatments.”

The study was supported by funds from the U.S. Department of Defense, Novartis, and the Swiss National Research Foundation. Dr. Chitnis has received personal compensation for consulting and advisory board membership from Biogen, Merck Serono, Novartis, and Sanofi.

[email protected]

SOURCE: Lokhande H et al. ACTRIMS Forum 2020, Abstract P018.

WEST PALM BEACH, FLA. – Serum neurofilament light (NfL) levels measured during the first several years after the clinical onset of multiple sclerosis (MS) may predict deep gray matter volumes at 10 years, according to research presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Researchers have begun to study longitudinal changes in serum NfL levels as a way to monitor axonal damage in patients with MS and see how they relate to other measures of neuronal loss, such as brain atrophy, and clinical outcomes over the long-term. “Deep gray matter volumes have been shown to correlate with neurological outcomes in MS patients. In particular, thalamic volume has been shown to correlate with measures of cognitive processing speed, such as the Symbol Digit Modalities Test,” said senior author Tanuja Chitnis, MD, professor of neurology at Harvard Medical School in Boston.

She and her colleagues sought to determine whether annual serum NfL measures could predict 10-year deep gray matter atrophy measured by volumetric MRI in patients with MS. They examined patients who were enrolled in the Comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study. Eligible participants were enrolled within 5 years of disease onset and had had annual blood samples drawn for as long as 10 years. In all, 122 patients met these criteria. The investigators measured serum NfL and compared it against deep gray matter volume in the thalamus, caudate, putamen, and globus pallidus from high-resolution 3-T MRI scans taken at year 10. Dr. Chitnis and colleagues assessed correlations between averaged annual NfL and 10-year MRI outcomes using univariate and multivariate linear regression models.

About 96% of participants were white, and about 2% were black. Approximately 73% of participants were female. Average age at the first symptom was 36 years, and average age at the first sample collection was 38 years.

The investigators found several negative associations between averaged NfL values and various MRI volumetric outcomes. Averaged annual serum NfL levels for the first 5 years were significantly and negatively associated with 10-year thalamic volumes in the unadjusted analysis. A 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000272 cm³ in thalamic volume. The association remained significant in an analysis adjusted for age, sex, and disease duration. In this analysis, a 1-pg/mL increase in the average sNfL value was associated with a decrease of 0.0000259 cm³ in thalamic volume. Analyzing serum NfL levels beyond year 5 did not reveal a stronger association. Serum NfL levels during the first 5 years accounted for about 24% of the variance in 10-year thalamic volumes. Dr. Chitnis and colleagues found similar statistically significant associations between serum NfL levels and caudate, putamen, and globus pallidus volumes. “Therefore, early serum NfL levels contribute to the identification of patients who may require highly effective therapies,” she said.

“We will continue to validate these results. As well, we are exploring other early biomarkers that increase predictive power of long-term outcomes in MS, with the goal of identifying patients most appropriate for high-efficacy treatments.”

The study was supported by funds from the U.S. Department of Defense, Novartis, and the Swiss National Research Foundation. Dr. Chitnis has received personal compensation for consulting and advisory board membership from Biogen, Merck Serono, Novartis, and Sanofi.

[email protected]

SOURCE: Lokhande H et al. ACTRIMS Forum 2020, Abstract P018.

WEST PALM BEACH, FLA. – Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis. Exploratory outcome measures of cognition, gait, and upper extremity function also improved.

Jake Remaly/MDedge News

The results do not mean that the treatment works. “We know that placebo works. I’m not here to tell you that the drug works. I’m just here to tell you that we have intriguing data,” said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.

The patients in the interim analysis represent about 25% of the target study population of 150 patients, Dr. Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.

Neuroprotective or remyelinating agents are an unmet need in MS, Dr. Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. Dr. Glanzman presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.

The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.

Among the first 34 enrolled participants, median LCLA improved by about five letters, Dr. Glanzman said. Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk). CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.

About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Dr. Glanzman said.

“These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection,” Dr. Glanzman said in a news release. “The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting.”

At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies – “Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis” – was published recently in Scientific Reports (2020 Feb 11;10[1]:1936). Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Dr. Glanzman said.

“We are studying the visual system in order to interrogate the nervous system as a whole,” he said. “The visual system is by far the most sensitive to change.” The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Dr. Glanzman added.

Dr. Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.

[email protected]

SOURCE: Glanzman R. ACTRIMS Forum 2020, Abstract.

WEST PALM BEACH, FLA. – Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis. Exploratory outcome measures of cognition, gait, and upper extremity function also improved.

Jake Remaly/MDedge News

The results do not mean that the treatment works. “We know that placebo works. I’m not here to tell you that the drug works. I’m just here to tell you that we have intriguing data,” said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.

The patients in the interim analysis represent about 25% of the target study population of 150 patients, Dr. Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.

Neuroprotective or remyelinating agents are an unmet need in MS, Dr. Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. Dr. Glanzman presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.

The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.

Among the first 34 enrolled participants, median LCLA improved by about five letters, Dr. Glanzman said. Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk). CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.

About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Dr. Glanzman said.

“These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection,” Dr. Glanzman said in a news release. “The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting.”

At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies – “Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis” – was published recently in Scientific Reports (2020 Feb 11;10[1]:1936). Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Dr. Glanzman said.

“We are studying the visual system in order to interrogate the nervous system as a whole,” he said. “The visual system is by far the most sensitive to change.” The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Dr. Glanzman added.

Dr. Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.

[email protected]

SOURCE: Glanzman R. ACTRIMS Forum 2020, Abstract.

WEST PALM BEACH, FLA. – Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis. Exploratory outcome measures of cognition, gait, and upper extremity function also improved.

Jake Remaly/MDedge News

The results do not mean that the treatment works. “We know that placebo works. I’m not here to tell you that the drug works. I’m just here to tell you that we have intriguing data,” said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.

The patients in the interim analysis represent about 25% of the target study population of 150 patients, Dr. Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.

Neuroprotective or remyelinating agents are an unmet need in MS, Dr. Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. Dr. Glanzman presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.

The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.

Among the first 34 enrolled participants, median LCLA improved by about five letters, Dr. Glanzman said. Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk). CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.

About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Dr. Glanzman said.

“These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection,” Dr. Glanzman said in a news release. “The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting.”

At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies – “Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis” – was published recently in Scientific Reports (2020 Feb 11;10[1]:1936). Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Dr. Glanzman said.

“We are studying the visual system in order to interrogate the nervous system as a whole,” he said. “The visual system is by far the most sensitive to change.” The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Dr. Glanzman added.

Dr. Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.

[email protected]

SOURCE: Glanzman R. ACTRIMS Forum 2020, Abstract.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

WEST PALM BEACH, FLA. – Cancer incidence among patients with multiple sclerosis (MS) treated after the advent of immune therapies showed an increase, compared with prior generations, according to a large study of Norwegian MS patients.

“We detected a similar cancer risk among MS patients, compared to the general Norwegian population before 1996, [however] MS patients had increased risk of cancer compared to the general population after 1996,” first author Nina Grytten, PhD, of the department of neurology at the Norwegian Multiple Sclerosis Centre, Bergen, Norway, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

“This finding suggests that clinicians should be aware of this increased risk of cancer when caring for MS patients.”

With the widespread use of disease-modifying therapies (DMTs) in patients with MS, such findings are always of interest to clinicians and patients alike, commented ACTRIMS president, Jeffrey A. Cohen, MD.

“Something that’s already on the mind of most people with MS is what are the long-term safety characteristics of these medicines because we’re talking about a life-long therapy for most people,” Dr. Cohen, who is the director of Experimental Therapeutics at the Mellen Center for MS Treatment and Research at the Cleveland Clinic, said in an interview.

“With such a large sample size and such a long study, this is on one hand reassuring and tells us the cancer risk is likely low, but it also suggests that it’s something we should pay attention to,” he said.

In previous research, Dr. Grytten and her team identified an increased risk of cancer among patients with MS in Norway, but conflicting results have been reported in other studies looking at cancer risk and MS.

The authors therefore sought to dig deeper into the risk in the Norwegian population, looking into the specifics of cancer incidence according to sex and the period of diagnosis.

For the study, they identified a total of 6,638 patients with MS from previous prevalence studies in Norway, as well as in the Norwegian MS Registry and Biobank.

The data from the cohort was matched with 36,957 Norwegian citizens without MS in a 5:1 ratio, with the participants matched according to age, gender, and county. The cohort was further linked to data from the Norwegian Cancer Registry for additional information on the year and type of cancer diagnosis, as well as cause and year of death data. The participants were born between 1930 and 1979.

Over the course of the full 65-year observation period, the cancer diagnosis rates were similar between participants with MS (774; 11.2%) and those without MS (4,017; 10.6%).

And in looking at cancer incidence rate ratios of those with MS, compared with controls between the years 1953 and 1995, the rate was similar (IRR, 1.05; 95% confidence interval, 0.97-1.14). However, after 1995, the rate increased, with a higher cancer incidence among MS patients, compared with those without MS (IRR, 1.40; 95% CI, 1.30-1.51).

Cancer rates were additionally higher among those with MS in cancers of various organs, including the brain (IRR, 1.75; 95% CI, 1.28-2.40), meninges (IRR, 2.28; 95% CI, 1.47-3.53), urinary organs (IRR, 2.06; 95% CI, 1.52-2.79), digestive system (IRR, 1.47; 95% CI, 1.20-1.80), endocrine glands (IRR, 1.64; 95% CI, 1.06-2.54), and respiratory organs (IRR, 2.05; 95% CI, 1.55-2.07).

Dr. Grytten noted, however, that the study cannot rule out various other possible causes for the differences. For instance, “cancer in urinary system and respiratory organs showed increased risk in MS both before and after introduction of disease-modifying therapies,” she noted. “Those are possibly caused by smoking, which is a habit more common among MS patients in Norway.”

Furthermore, “increased cancer in the central nervous system in MS could possibly be explained by frequent use of magnetic resonance imaging and the ability to detect CNS cancer at early stages.”

“There is increasing evidence that patients with MS are also more susceptible to other diseases, and increased cancer risk seems to be one of these comorbidities.”

However, the finding that increased cancers were observed after 1996 in other organs in MS patients as well does raise the issue of a possible role of DMTs.

Of note, mitoxantrone has been associated with an increased risk of leukemia and colorectal cancer.

And “other immunosuppressant drugs, including the MS drug fingolimod, are believed to possibly be linked to an increased cancer risk, although evidence has not yet been established,” Dr. Grytten said.

“The increased risk of cancer associated with MS was detected in the era of disease-modifying treatment of MS, and this association suggests that DMTs might possibly increase cancer risk.”

In general, “clinicians should be aware of comorbidity in MS,” Dr. Grytten said. “More data is needed on the long-time effects of immunomodulatory treatment.”

Dr. Cohen added that, in addition to mitoxantrone, azathioprine and cyclophosphamide have shown risk, but “clinical trials and follow-up studies of individual MS DMTs have not shown clear cut increased risk of cancer, which is reassuring.”

“Nevertheless, this study suggests that, in aggregate, there may be a mild increased risk. There are many other potential explanations, so the research needs to be followed up,” he said.

Dr. Cohen reported receiving personal compensation for consulting for Adamas, Convelo, MedDay, Mylan, and Population Council; and serving as an Editor of Multiple Sclerosis Journal.

SOURCE: Torkildsen NG et al. ACTRIMS Forum 2020, Abstract P126.

WEST PALM BEACH, FLA. – Patients with pediatric-onset multiple sclerosis (POMS) have less higher education and greater use of high-efficacy disease-modifying therapy (DMT), compared with patients with adult-onset MS (AOMS), according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Among patients with POMS, researchers also have observed an association between fatigue and mood disorders on one hand and DMT choice on the other hand. “These findings confirm the unique features of POMS and suggest that DMT choice in POMS and AOMS may influence the frequency of fatigue and mood disorders,” said Mary Rensel, MD, staff neurologist in neuroimmunology at Cleveland Clinic’s Mellen Center for MS Treatment and Research, and colleagues.

POMS is defined as MS onset before age 18, and the disease characteristics of POMS and AOMS are distinct. The former diagnosis is rare, which has limited the amount of data collected on POMS to date.

MS Partners Advancing Technology and Health Solutions (MS-PATHS), sponsored by Biogen, is a multicenter initiative in which researchers collect MS performance measures longitudinally at each patient visit. MS-PATHS data include sociodemographic information, patient-reported outcomes (PROs), functional outcomes (FOs), MS phenotype, and DMT. Using MS-PATHS data, Dr. Rensel and colleagues sought to determine differences in sociodemographics, MS phenotype, PRO, FO, and DMT among patients with POMS and between patients with POMS and those with AOMS.

The investigators analyzed data cut 9 of the MS-PATHS database for their study. They included 637 participants with POMS and matched them with patients with AOMS, based on disease duration, in a 1:5 ratio. Dr. Rensel and colleagues categorized DMTs as high, mid, or low efficacy. They calculated descriptive statistics to characterize the study population. In addition, they compared MS FOs and PROs in the matched cohort using the Wilcoxon rank-sum test. Finally, linear regression analysis allowed the investigators to identify differences in the data set, while adjusting for important covariates.

The matched cohort included 5,857 patients with AOMS and 600 patients with POMS. The patients with AOMS had an average age of 49.8 years. About 87.5% of these patients were white, and 73.5% were female. The POMS patients had an average age of 31.49 years. Overall, 76.7% of these patients were white, and 73.2% were female. Dr. Rensel and colleagues found significant differences between the two groups in age at encounter, disease duration, race, insurance, Patient Determined Disease Steps (PDDS), education, employment, FOs, PROs, and DMT.

Patients with POMS used high-efficacy DMT more frequently than those with AOMS. The rate of depression was similar between patients with AOMS and those with POMS. Depression, anxiety, and fatigue were associated with DMT potency in AOMS, and anxiety and fatigue were associated with DMT groups in POMS.

Racial differences between POMS and AOMS have been reported previously, said Dr. Rensel. First-generation immigrant children have an increased risk of POMS, compared with other children. “In our data set, we had more Asians, more blacks, and fewer Caucasians in the POMS group,” said Dr. Rensel. People from a socioeconomically challenged environment have an increased risk of POMS, and this observation may explain the difference in insurance coverage between the POMS and AOMS groups, she added. Socioeconomic challenges also may explain the difference in the rate of higher education between the two groups.

“Why were the POMS cases associated with higher-efficacy DMT when only one oral MS DMT is [Food and Drug Administration]-approved for POMS?” Dr. Rensel asked. “This is likely due to the fact that POMS cases tend to have higher disease activity with more relapses and more brain lesions, leading to the choice of higher efficacy DMTs that are currently not FDA-approved for POMS.”

These data “may help [clinicians] caring for kids and teens, especially non-Caucasian [patients], to consider MS on the differential diagnosis,” Dr. Rensel added. “Mood disorders in POMS were as common as mood disorders in AOMS, so these should be screened for in this POMS population.”

Dr. Rensel has received funding for consulting, research, or patient education from Biogen, Genentech, Genzyme, Medimmune, MSAA, NMSS, Novartis, TSerono, and Teva.

[email protected]

SOURCE: Rensel M et al. ACTRIMS Forum 2020, Abstract P042.

WEST PALM BEACH, FLA. – Patients with pediatric-onset multiple sclerosis (POMS) have less higher education and greater use of high-efficacy disease-modifying therapy (DMT), compared with patients with adult-onset MS (AOMS), according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Among patients with POMS, researchers also have observed an association between fatigue and mood disorders on one hand and DMT choice on the other hand. “These findings confirm the unique features of POMS and suggest that DMT choice in POMS and AOMS may influence the frequency of fatigue and mood disorders,” said Mary Rensel, MD, staff neurologist in neuroimmunology at Cleveland Clinic’s Mellen Center for MS Treatment and Research, and colleagues.

POMS is defined as MS onset before age 18, and the disease characteristics of POMS and AOMS are distinct. The former diagnosis is rare, which has limited the amount of data collected on POMS to date.

MS Partners Advancing Technology and Health Solutions (MS-PATHS), sponsored by Biogen, is a multicenter initiative in which researchers collect MS performance measures longitudinally at each patient visit. MS-PATHS data include sociodemographic information, patient-reported outcomes (PROs), functional outcomes (FOs), MS phenotype, and DMT. Using MS-PATHS data, Dr. Rensel and colleagues sought to determine differences in sociodemographics, MS phenotype, PRO, FO, and DMT among patients with POMS and between patients with POMS and those with AOMS.

The investigators analyzed data cut 9 of the MS-PATHS database for their study. They included 637 participants with POMS and matched them with patients with AOMS, based on disease duration, in a 1:5 ratio. Dr. Rensel and colleagues categorized DMTs as high, mid, or low efficacy. They calculated descriptive statistics to characterize the study population. In addition, they compared MS FOs and PROs in the matched cohort using the Wilcoxon rank-sum test. Finally, linear regression analysis allowed the investigators to identify differences in the data set, while adjusting for important covariates.

The matched cohort included 5,857 patients with AOMS and 600 patients with POMS. The patients with AOMS had an average age of 49.8 years. About 87.5% of these patients were white, and 73.5% were female. The POMS patients had an average age of 31.49 years. Overall, 76.7% of these patients were white, and 73.2% were female. Dr. Rensel and colleagues found significant differences between the two groups in age at encounter, disease duration, race, insurance, Patient Determined Disease Steps (PDDS), education, employment, FOs, PROs, and DMT.

Patients with POMS used high-efficacy DMT more frequently than those with AOMS. The rate of depression was similar between patients with AOMS and those with POMS. Depression, anxiety, and fatigue were associated with DMT potency in AOMS, and anxiety and fatigue were associated with DMT groups in POMS.

Racial differences between POMS and AOMS have been reported previously, said Dr. Rensel. First-generation immigrant children have an increased risk of POMS, compared with other children. “In our data set, we had more Asians, more blacks, and fewer Caucasians in the POMS group,” said Dr. Rensel. People from a socioeconomically challenged environment have an increased risk of POMS, and this observation may explain the difference in insurance coverage between the POMS and AOMS groups, she added. Socioeconomic challenges also may explain the difference in the rate of higher education between the two groups.

“Why were the POMS cases associated with higher-efficacy DMT when only one oral MS DMT is [Food and Drug Administration]-approved for POMS?” Dr. Rensel asked. “This is likely due to the fact that POMS cases tend to have higher disease activity with more relapses and more brain lesions, leading to the choice of higher efficacy DMTs that are currently not FDA-approved for POMS.”

These data “may help [clinicians] caring for kids and teens, especially non-Caucasian [patients], to consider MS on the differential diagnosis,” Dr. Rensel added. “Mood disorders in POMS were as common as mood disorders in AOMS, so these should be screened for in this POMS population.”

Dr. Rensel has received funding for consulting, research, or patient education from Biogen, Genentech, Genzyme, Medimmune, MSAA, NMSS, Novartis, TSerono, and Teva.

[email protected]

SOURCE: Rensel M et al. ACTRIMS Forum 2020, Abstract P042.

WEST PALM BEACH, FLA. – Patients with pediatric-onset multiple sclerosis (POMS) have less higher education and greater use of high-efficacy disease-modifying therapy (DMT), compared with patients with adult-onset MS (AOMS), according to data presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Among patients with POMS, researchers also have observed an association between fatigue and mood disorders on one hand and DMT choice on the other hand. “These findings confirm the unique features of POMS and suggest that DMT choice in POMS and AOMS may influence the frequency of fatigue and mood disorders,” said Mary Rensel, MD, staff neurologist in neuroimmunology at Cleveland Clinic’s Mellen Center for MS Treatment and Research, and colleagues.

POMS is defined as MS onset before age 18, and the disease characteristics of POMS and AOMS are distinct. The former diagnosis is rare, which has limited the amount of data collected on POMS to date.

MS Partners Advancing Technology and Health Solutions (MS-PATHS), sponsored by Biogen, is a multicenter initiative in which researchers collect MS performance measures longitudinally at each patient visit. MS-PATHS data include sociodemographic information, patient-reported outcomes (PROs), functional outcomes (FOs), MS phenotype, and DMT. Using MS-PATHS data, Dr. Rensel and colleagues sought to determine differences in sociodemographics, MS phenotype, PRO, FO, and DMT among patients with POMS and between patients with POMS and those with AOMS.

The investigators analyzed data cut 9 of the MS-PATHS database for their study. They included 637 participants with POMS and matched them with patients with AOMS, based on disease duration, in a 1:5 ratio. Dr. Rensel and colleagues categorized DMTs as high, mid, or low efficacy. They calculated descriptive statistics to characterize the study population. In addition, they compared MS FOs and PROs in the matched cohort using the Wilcoxon rank-sum test. Finally, linear regression analysis allowed the investigators to identify differences in the data set, while adjusting for important covariates.

The matched cohort included 5,857 patients with AOMS and 600 patients with POMS. The patients with AOMS had an average age of 49.8 years. About 87.5% of these patients were white, and 73.5% were female. The POMS patients had an average age of 31.49 years. Overall, 76.7% of these patients were white, and 73.2% were female. Dr. Rensel and colleagues found significant differences between the two groups in age at encounter, disease duration, race, insurance, Patient Determined Disease Steps (PDDS), education, employment, FOs, PROs, and DMT.

Patients with POMS used high-efficacy DMT more frequently than those with AOMS. The rate of depression was similar between patients with AOMS and those with POMS. Depression, anxiety, and fatigue were associated with DMT potency in AOMS, and anxiety and fatigue were associated with DMT groups in POMS.

Racial differences between POMS and AOMS have been reported previously, said Dr. Rensel. First-generation immigrant children have an increased risk of POMS, compared with other children. “In our data set, we had more Asians, more blacks, and fewer Caucasians in the POMS group,” said Dr. Rensel. People from a socioeconomically challenged environment have an increased risk of POMS, and this observation may explain the difference in insurance coverage between the POMS and AOMS groups, she added. Socioeconomic challenges also may explain the difference in the rate of higher education between the two groups.

“Why were the POMS cases associated with higher-efficacy DMT when only one oral MS DMT is [Food and Drug Administration]-approved for POMS?” Dr. Rensel asked. “This is likely due to the fact that POMS cases tend to have higher disease activity with more relapses and more brain lesions, leading to the choice of higher efficacy DMTs that are currently not FDA-approved for POMS.”

These data “may help [clinicians] caring for kids and teens, especially non-Caucasian [patients], to consider MS on the differential diagnosis,” Dr. Rensel added. “Mood disorders in POMS were as common as mood disorders in AOMS, so these should be screened for in this POMS population.”

Dr. Rensel has received funding for consulting, research, or patient education from Biogen, Genentech, Genzyme, Medimmune, MSAA, NMSS, Novartis, TSerono, and Teva.

[email protected]

SOURCE: Rensel M et al. ACTRIMS Forum 2020, Abstract P042.