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What other drugs do patients take when they start MS therapy?
SEATTLE – , according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. The likelihood of particular comorbidities and concomitant medications varies by age and sex, researchers reported.
“This may have implications for MS treatment,” said study author Jacqueline Nicholas, MD, MPH, of Ohio Multiple Sclerosis Center in Columbus and her research colleagues. “A better understanding of the effects of comorbidities and concomitant medications on the effectiveness and safety of DMDs is needed to support clinical decision making.”
Researchers have examined comorbidities in patients with MS, but concomitant medication use among patients starting DMDs is poorly understood, the authors said.
To study this question, Dr. Nicholas and colleagues analyzed retrospective administrative claims data from IQVIA’s Real-World Data Adjudicated Claims–U.S. database from Jan. 1, 2010, to June 30, 2017. Their analysis included patients with two or more MS diagnosis claims and at least one DMD claim between Jan. 1, 2011, and June 30, 2015. Eligible patients were aged 18-63 years and had continuous eligibility with commercial insurance 1 year before and 2 years after DMD initiation. In addition, patients had no evidence of DMD use during the 1-year baseline period.
The investigators used International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes and claims to evaluate patients’ comorbidities and concomitant medications during the study period.
The researchers identified 8,251 eligible patients. Patients had a mean age of 43.2 years, and 75.5% were female. Average baseline Charlson comorbidity score was 0.41. In the 2 years after DMD initiation, common comorbid diagnoses were hyperlipidemia (30.0%), hypertension (28.2%), gastrointestinal disorders (26.2%), depression (25.5%), and anxiety (20.1%).
Common concomitant medications included antibiotics (70.6%); analgesics (57.0%); corticosteroids (52.0%); antidepressants (47.7%); anticonvulsants (46.7%); anxiolytics, sedatives, or hypnotics (43.2%); spasticity medications (36.2%); and muscle relaxants (35.4%).
Most comorbidities and many medications, including bladder and antifatigue medications, were more common among patients aged 55 years and older. Hyperlipidemia, hypertension, and diabetes were more likely in males than in females. Females were more likely to have gastrointestinal disease, depression, thyroid disease, anxiety, lung disease, and arthritis. In addition, females were more likely than males to use many of the concomitant medications.
Dr. Nicholas disclosed grant support from EMD Serono. A coauthor is an employee of Health Services Consulting Corporation and received funding from EMD Serono to conduct the study. Other coauthors are employees of EMD Serono.
SEATTLE – , according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. The likelihood of particular comorbidities and concomitant medications varies by age and sex, researchers reported.
“This may have implications for MS treatment,” said study author Jacqueline Nicholas, MD, MPH, of Ohio Multiple Sclerosis Center in Columbus and her research colleagues. “A better understanding of the effects of comorbidities and concomitant medications on the effectiveness and safety of DMDs is needed to support clinical decision making.”
Researchers have examined comorbidities in patients with MS, but concomitant medication use among patients starting DMDs is poorly understood, the authors said.
To study this question, Dr. Nicholas and colleagues analyzed retrospective administrative claims data from IQVIA’s Real-World Data Adjudicated Claims–U.S. database from Jan. 1, 2010, to June 30, 2017. Their analysis included patients with two or more MS diagnosis claims and at least one DMD claim between Jan. 1, 2011, and June 30, 2015. Eligible patients were aged 18-63 years and had continuous eligibility with commercial insurance 1 year before and 2 years after DMD initiation. In addition, patients had no evidence of DMD use during the 1-year baseline period.
The investigators used International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes and claims to evaluate patients’ comorbidities and concomitant medications during the study period.
The researchers identified 8,251 eligible patients. Patients had a mean age of 43.2 years, and 75.5% were female. Average baseline Charlson comorbidity score was 0.41. In the 2 years after DMD initiation, common comorbid diagnoses were hyperlipidemia (30.0%), hypertension (28.2%), gastrointestinal disorders (26.2%), depression (25.5%), and anxiety (20.1%).
Common concomitant medications included antibiotics (70.6%); analgesics (57.0%); corticosteroids (52.0%); antidepressants (47.7%); anticonvulsants (46.7%); anxiolytics, sedatives, or hypnotics (43.2%); spasticity medications (36.2%); and muscle relaxants (35.4%).
Most comorbidities and many medications, including bladder and antifatigue medications, were more common among patients aged 55 years and older. Hyperlipidemia, hypertension, and diabetes were more likely in males than in females. Females were more likely to have gastrointestinal disease, depression, thyroid disease, anxiety, lung disease, and arthritis. In addition, females were more likely than males to use many of the concomitant medications.
Dr. Nicholas disclosed grant support from EMD Serono. A coauthor is an employee of Health Services Consulting Corporation and received funding from EMD Serono to conduct the study. Other coauthors are employees of EMD Serono.
SEATTLE – , according to research presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. The likelihood of particular comorbidities and concomitant medications varies by age and sex, researchers reported.
“This may have implications for MS treatment,” said study author Jacqueline Nicholas, MD, MPH, of Ohio Multiple Sclerosis Center in Columbus and her research colleagues. “A better understanding of the effects of comorbidities and concomitant medications on the effectiveness and safety of DMDs is needed to support clinical decision making.”
Researchers have examined comorbidities in patients with MS, but concomitant medication use among patients starting DMDs is poorly understood, the authors said.
To study this question, Dr. Nicholas and colleagues analyzed retrospective administrative claims data from IQVIA’s Real-World Data Adjudicated Claims–U.S. database from Jan. 1, 2010, to June 30, 2017. Their analysis included patients with two or more MS diagnosis claims and at least one DMD claim between Jan. 1, 2011, and June 30, 2015. Eligible patients were aged 18-63 years and had continuous eligibility with commercial insurance 1 year before and 2 years after DMD initiation. In addition, patients had no evidence of DMD use during the 1-year baseline period.
The investigators used International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes and claims to evaluate patients’ comorbidities and concomitant medications during the study period.
The researchers identified 8,251 eligible patients. Patients had a mean age of 43.2 years, and 75.5% were female. Average baseline Charlson comorbidity score was 0.41. In the 2 years after DMD initiation, common comorbid diagnoses were hyperlipidemia (30.0%), hypertension (28.2%), gastrointestinal disorders (26.2%), depression (25.5%), and anxiety (20.1%).
Common concomitant medications included antibiotics (70.6%); analgesics (57.0%); corticosteroids (52.0%); antidepressants (47.7%); anticonvulsants (46.7%); anxiolytics, sedatives, or hypnotics (43.2%); spasticity medications (36.2%); and muscle relaxants (35.4%).
Most comorbidities and many medications, including bladder and antifatigue medications, were more common among patients aged 55 years and older. Hyperlipidemia, hypertension, and diabetes were more likely in males than in females. Females were more likely to have gastrointestinal disease, depression, thyroid disease, anxiety, lung disease, and arthritis. In addition, females were more likely than males to use many of the concomitant medications.
Dr. Nicholas disclosed grant support from EMD Serono. A coauthor is an employee of Health Services Consulting Corporation and received funding from EMD Serono to conduct the study. Other coauthors are employees of EMD Serono.
REPORTING FROM CMSC 2019
Key clinical point: The effect of comorbidities and concomitant medications on the effectiveness and safety of disease-modifying drugs for multiple sclerosis requires further study.
Major finding: In one analysis, common concomitant medications included antibiotics (70.6%), analgesics (57.0%), corticosteroids (52.0%), antidepressants (47.7%), and anticonvulsants (46.7%).
Study details: An analysis of retrospective administrative claims data from 8,251 patients with MS.
Disclosures: Dr. Nicholas disclosed grant support from EMD Serono. A coauthor is an employee of Health Services Consulting Corporation and received funding from EMD Serono to conduct the study. Other coauthors are employees of EMD Serono.
Anxiety and fatigue impair processing speed in MS
SEATTLE – (MS), according to data described at the annual meeting of the Consortium of Multiple Sclerosis Centers. Increased anxiety is associated with slower processing speed in the context of increasing cognitive fatigue. “This [finding] has implications on development of cognitive remediation strategies, which may aim to target patient fatigue or anxiety to improve processing speed,” said Caroline Altaras, a doctoral candidate at Yeshiva University in New York, and colleagues.
Approximately 90% of patients with MS have fatigue, which can be a highly debilitating symptom. Fatigue often is understood to include motor fatigue (difficulty maintaining physical stamina) and cognitive fatigue (difficulty maintaining mental stamina). MS-related fatigue decreases patients’ quality of life, including cognitive functioning.
Anxiety is a psychiatric comorbidity that is highly prevalent in MS and that has a bidirectional association with fatigue. Anxiety and fatigue independently impair cognitive function.
Impaired processing speed is the most common cognitive impairment among patients with MS. Ms. Altaras and colleagues conducted a study to analyze how anxiety and fatigue interact to affect processing speed in MS. They evaluated total fatigue, cognitive fatigue, and motor fatigue separately. The investigators collected data from 183 patients with MS who had been referred by physicians for neuropsychological testing at the MS Center at Holy Name Medical Center in Teaneck, New Jersey. Researchers measured patients’ anxiety and fatigue using the Hospital Anxiety and Depression Scale (HADS, a self-reported measure) and the Fatigue Scale for Motor and Cognitive Functions (FSMC), which measures cognitive fatigue and motor fatigue. Patients also took the Symbol Digit Modalities Test (SDMT), a neuropsychological measure of processing speed. Ms. Altaras and colleagues created three multivariate general linear models using SPSS 25.0 to test the hypothesized relationships, using fatigue types (cognitive, motor, and total) as separate outcomes. The investigators controlled their analyses for gender, age, and education.
The researchers found a significant interaction effect of cognitive fatigue and anxiety on SDMT score. Specifically, patients with MS and minimal anxiety and cognitive fatigue had similar SDMT performance; as anxiety increased, patients who had increased cognitive fatigue demonstrated worse performance on the SDMT. Ms. Altaras and colleagues observed that SDMT performance improved slightly with worsening anxiety when cognitive fatigue was minimal. Although total fatigue interacted significantly with anxiety to affect SDMT performance, motor fatigue did not, which suggests that the effects of total fatigue largely resulted from cognitive fatigue.
The study had no outside financial support, and the authors reported no disclosures.
SEATTLE – (MS), according to data described at the annual meeting of the Consortium of Multiple Sclerosis Centers. Increased anxiety is associated with slower processing speed in the context of increasing cognitive fatigue. “This [finding] has implications on development of cognitive remediation strategies, which may aim to target patient fatigue or anxiety to improve processing speed,” said Caroline Altaras, a doctoral candidate at Yeshiva University in New York, and colleagues.
Approximately 90% of patients with MS have fatigue, which can be a highly debilitating symptom. Fatigue often is understood to include motor fatigue (difficulty maintaining physical stamina) and cognitive fatigue (difficulty maintaining mental stamina). MS-related fatigue decreases patients’ quality of life, including cognitive functioning.
Anxiety is a psychiatric comorbidity that is highly prevalent in MS and that has a bidirectional association with fatigue. Anxiety and fatigue independently impair cognitive function.
Impaired processing speed is the most common cognitive impairment among patients with MS. Ms. Altaras and colleagues conducted a study to analyze how anxiety and fatigue interact to affect processing speed in MS. They evaluated total fatigue, cognitive fatigue, and motor fatigue separately. The investigators collected data from 183 patients with MS who had been referred by physicians for neuropsychological testing at the MS Center at Holy Name Medical Center in Teaneck, New Jersey. Researchers measured patients’ anxiety and fatigue using the Hospital Anxiety and Depression Scale (HADS, a self-reported measure) and the Fatigue Scale for Motor and Cognitive Functions (FSMC), which measures cognitive fatigue and motor fatigue. Patients also took the Symbol Digit Modalities Test (SDMT), a neuropsychological measure of processing speed. Ms. Altaras and colleagues created three multivariate general linear models using SPSS 25.0 to test the hypothesized relationships, using fatigue types (cognitive, motor, and total) as separate outcomes. The investigators controlled their analyses for gender, age, and education.
The researchers found a significant interaction effect of cognitive fatigue and anxiety on SDMT score. Specifically, patients with MS and minimal anxiety and cognitive fatigue had similar SDMT performance; as anxiety increased, patients who had increased cognitive fatigue demonstrated worse performance on the SDMT. Ms. Altaras and colleagues observed that SDMT performance improved slightly with worsening anxiety when cognitive fatigue was minimal. Although total fatigue interacted significantly with anxiety to affect SDMT performance, motor fatigue did not, which suggests that the effects of total fatigue largely resulted from cognitive fatigue.
The study had no outside financial support, and the authors reported no disclosures.
SEATTLE – (MS), according to data described at the annual meeting of the Consortium of Multiple Sclerosis Centers. Increased anxiety is associated with slower processing speed in the context of increasing cognitive fatigue. “This [finding] has implications on development of cognitive remediation strategies, which may aim to target patient fatigue or anxiety to improve processing speed,” said Caroline Altaras, a doctoral candidate at Yeshiva University in New York, and colleagues.
Approximately 90% of patients with MS have fatigue, which can be a highly debilitating symptom. Fatigue often is understood to include motor fatigue (difficulty maintaining physical stamina) and cognitive fatigue (difficulty maintaining mental stamina). MS-related fatigue decreases patients’ quality of life, including cognitive functioning.
Anxiety is a psychiatric comorbidity that is highly prevalent in MS and that has a bidirectional association with fatigue. Anxiety and fatigue independently impair cognitive function.
Impaired processing speed is the most common cognitive impairment among patients with MS. Ms. Altaras and colleagues conducted a study to analyze how anxiety and fatigue interact to affect processing speed in MS. They evaluated total fatigue, cognitive fatigue, and motor fatigue separately. The investigators collected data from 183 patients with MS who had been referred by physicians for neuropsychological testing at the MS Center at Holy Name Medical Center in Teaneck, New Jersey. Researchers measured patients’ anxiety and fatigue using the Hospital Anxiety and Depression Scale (HADS, a self-reported measure) and the Fatigue Scale for Motor and Cognitive Functions (FSMC), which measures cognitive fatigue and motor fatigue. Patients also took the Symbol Digit Modalities Test (SDMT), a neuropsychological measure of processing speed. Ms. Altaras and colleagues created three multivariate general linear models using SPSS 25.0 to test the hypothesized relationships, using fatigue types (cognitive, motor, and total) as separate outcomes. The investigators controlled their analyses for gender, age, and education.
The researchers found a significant interaction effect of cognitive fatigue and anxiety on SDMT score. Specifically, patients with MS and minimal anxiety and cognitive fatigue had similar SDMT performance; as anxiety increased, patients who had increased cognitive fatigue demonstrated worse performance on the SDMT. Ms. Altaras and colleagues observed that SDMT performance improved slightly with worsening anxiety when cognitive fatigue was minimal. Although total fatigue interacted significantly with anxiety to affect SDMT performance, motor fatigue did not, which suggests that the effects of total fatigue largely resulted from cognitive fatigue.
The study had no outside financial support, and the authors reported no disclosures.
REPORTING FROM CMSC 2019
Key clinical point: Anxiety and fatigue interact to affect processing speed in MS.
Major finding: Cognitive fatigue and anxiety interact to affect performance on the Symbol Digit Modalities Test.
Study details: A prospective study of 183 patients with MS referred for neuropsychological testing.
Disclosures: The study had no outside funding, and the investigators had no disclosures.
MS significantly affects employment and home activities
SEATTLE – according to data presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. The disease appears to prevent people from achieving their full potential at work and at home, largely because of its associated fatigue, said the researchers. “The economic impact of identifying an effective treatment for this symptom of MS cannot be overstated,” said Terrie Livingston, PharmD, head of patient outcomes and solutions at EMD Serono in Wayland, Massachusetts, and colleagues.
The research results from an initiative by the North American Registry for Care and Research in MS (NARCRMS). Since December 2016, NARCRMS has prospectively collected clinical and imaging data, information about patients’ health care economics, and data about the effects of MS on daily life. To examine the economic impact of MS and to help implement health economics outcomes research (HEOR) in decision-making processes, NARCRMS established the HEOR Advisory Group in 2017. The registry created a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire, both of which were incorporated into the existing case report forms. Patients complete these questionnaires at enrollment and at annual and exacerbation visits.
As of January 2, 2019, NARCRMS had enrolled 378 people with MS into the registry, and 368 had completed the HEOR case report forms. Among the respondents, 270 (73%) are employed either full or part time. During the week before reporting, 39 respondents (11%) reported that MS kept them from work, 93 (25%) reported that MS affected their work, 105 (29%) reported that MS stopped them from finishing household chores, and 140 (38%) reported that MS affected their household chores. Fatigue was the symptom most commonly reported to affect work and household chores. In the 3 months before reporting, 13 patients (4%) had inpatient hospital stays, 24 patients (7%) visited the ED, 71 patients (19%) visited a general practitioner, and 296 (80%) patients visited a neurologist.
The study had no sponsor. Several of the study authors reported receiving compensation from companies such as Biogen, Celgene, Genentech, Novartis, Sanofi Genzyme, and Teva.
SEATTLE – according to data presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. The disease appears to prevent people from achieving their full potential at work and at home, largely because of its associated fatigue, said the researchers. “The economic impact of identifying an effective treatment for this symptom of MS cannot be overstated,” said Terrie Livingston, PharmD, head of patient outcomes and solutions at EMD Serono in Wayland, Massachusetts, and colleagues.
The research results from an initiative by the North American Registry for Care and Research in MS (NARCRMS). Since December 2016, NARCRMS has prospectively collected clinical and imaging data, information about patients’ health care economics, and data about the effects of MS on daily life. To examine the economic impact of MS and to help implement health economics outcomes research (HEOR) in decision-making processes, NARCRMS established the HEOR Advisory Group in 2017. The registry created a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire, both of which were incorporated into the existing case report forms. Patients complete these questionnaires at enrollment and at annual and exacerbation visits.
As of January 2, 2019, NARCRMS had enrolled 378 people with MS into the registry, and 368 had completed the HEOR case report forms. Among the respondents, 270 (73%) are employed either full or part time. During the week before reporting, 39 respondents (11%) reported that MS kept them from work, 93 (25%) reported that MS affected their work, 105 (29%) reported that MS stopped them from finishing household chores, and 140 (38%) reported that MS affected their household chores. Fatigue was the symptom most commonly reported to affect work and household chores. In the 3 months before reporting, 13 patients (4%) had inpatient hospital stays, 24 patients (7%) visited the ED, 71 patients (19%) visited a general practitioner, and 296 (80%) patients visited a neurologist.
The study had no sponsor. Several of the study authors reported receiving compensation from companies such as Biogen, Celgene, Genentech, Novartis, Sanofi Genzyme, and Teva.
SEATTLE – according to data presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. The disease appears to prevent people from achieving their full potential at work and at home, largely because of its associated fatigue, said the researchers. “The economic impact of identifying an effective treatment for this symptom of MS cannot be overstated,” said Terrie Livingston, PharmD, head of patient outcomes and solutions at EMD Serono in Wayland, Massachusetts, and colleagues.
The research results from an initiative by the North American Registry for Care and Research in MS (NARCRMS). Since December 2016, NARCRMS has prospectively collected clinical and imaging data, information about patients’ health care economics, and data about the effects of MS on daily life. To examine the economic impact of MS and to help implement health economics outcomes research (HEOR) in decision-making processes, NARCRMS established the HEOR Advisory Group in 2017. The registry created a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire, both of which were incorporated into the existing case report forms. Patients complete these questionnaires at enrollment and at annual and exacerbation visits.
As of January 2, 2019, NARCRMS had enrolled 378 people with MS into the registry, and 368 had completed the HEOR case report forms. Among the respondents, 270 (73%) are employed either full or part time. During the week before reporting, 39 respondents (11%) reported that MS kept them from work, 93 (25%) reported that MS affected their work, 105 (29%) reported that MS stopped them from finishing household chores, and 140 (38%) reported that MS affected their household chores. Fatigue was the symptom most commonly reported to affect work and household chores. In the 3 months before reporting, 13 patients (4%) had inpatient hospital stays, 24 patients (7%) visited the ED, 71 patients (19%) visited a general practitioner, and 296 (80%) patients visited a neurologist.
The study had no sponsor. Several of the study authors reported receiving compensation from companies such as Biogen, Celgene, Genentech, Novartis, Sanofi Genzyme, and Teva.
REPORTING FROM CMSC 2019
Key clinical point: Fatigue is the most common symptom preventing people with MS from completing work or chores.
Major finding: Approximately 28% of people with MS may be underemployed or unemployed.
Study details: An analysis of registry data, including questionnaires for 368 patients with MS.
Disclosures: The study had no sponsor. Dr. Livingston is an employee of EMD Serono.
Alemtuzumab increases the likelihood of disability improvement in MS
Seattle – , according to a pooled analysis presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Patients who achieved this outcome had improvement in several functional systems, regardless of their baseline EDSS scores. “These results suggest a broad and prolonged effect of alemtuzumab on disability improvement and a potential for changing the MS disease course,” said Samuel F. Hunter, MD, a neurologist and psychiatrist at the Advanced Neurosciences Institute in Franklin, Tenn., and colleagues.
The researchers’ findings come from their analysis of pooled data from the CARE-MS I and CARE-MS II trials. Those studies indicated that alemtuzumab improved clinical and MRI outcomes over 2 years in relapsing-remitting MS, compared with interferon beta-1a. In a 4-year extension, alemtuzumab’s efficacy was maintained, and 81% of participants continued in the study until year 6. In addition, 34% of alemtuzumab-treated patients in CARE-MS I and 43% of alemtuzumab-treated patients in CARE-MS II achieved 6-month confirmed disability improvement. The relationship between baseline disability levels and the achievement of disability improvement is not well understood, however.
Dr. Hunter and colleagues conducted a pooled analysis of CARE-MS I and CARE-MS II data to evaluate how baseline disability affects improvements in each functional system in patients treated with alemtuzumab over 6 years. In those studies, patients received two 12-mg/day courses of alemtuzumab: a 5-day course at baseline and a 3-day course 12 months later. Additional treatment with alemtuzumab or other disease-modifying therapies was provided as needed during the extension study.
The investigators defined confirmed disability improvement as a decrease of 1 or more points in EDSS score confirmed over 6 months among patients with a baseline EDSS score of 2 or higher. Improvement (i.e., a decrease of 1 or more points) or stability (i.e., no change) in each of the functional system scores was assessed in patients with confirmed disability improvement, stratified by baseline EDSS scores. Patients were grouped according to whether their baseline EDSS scores were 2.0-2.5, 3.0-3.5, 4.0-4.5, 5.0-5.5, or 6.0-6.5.
A total of 208 of 565 patients (37%) achieved 6-month confirmed disability improvement through year 6. This outcome was achieved by the highest percentages of patients with baseline EDSS scores of 4.0-4.5 (57%) and 3.0-3.5 (44%), followed by those with baseline EDSS scores of 5.0-5.5 (28%) and 2.0-2.5 (27%). No patients with baseline EDSS scores of 6.0-6.5 achieved confirmed disability improvement.
At 6 months after onset of confirmed disability improvement, patients within each baseline EDSS group showed stability or improvement in each individual functional system. The proportion of stable or improved patients was 94% or greater in the 2.0-2.5 group, 92% or greater in the 3.0-3.5 group, 88% or greater in the 4.0-4.5 group, and 75% or greater in the 5.0-5.5 group. Between 67% and 76% of patients achieved improvements in two or more functional systems. Improvements were most frequent in the pyramidal (13% to 50%), sensory (42% to 50%), and cerebellar (13% to 55%) functional systems.
Sanofi, Bayer HealthCare Pharmaceuticals supported the study. Dr. Hunter received grants and financial support from AbbVie, Actelion, Acorda, Adamas, Alkermes, Avanir, Bayer HealthCare, Biogen, Novartis, Osmotica, Questcor, Roche, Sanofi, Synthon, and Teva.
SOURCE: Hunter SF et al. CMSC 2019. Abstract DXT08.
Seattle – , according to a pooled analysis presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Patients who achieved this outcome had improvement in several functional systems, regardless of their baseline EDSS scores. “These results suggest a broad and prolonged effect of alemtuzumab on disability improvement and a potential for changing the MS disease course,” said Samuel F. Hunter, MD, a neurologist and psychiatrist at the Advanced Neurosciences Institute in Franklin, Tenn., and colleagues.
The researchers’ findings come from their analysis of pooled data from the CARE-MS I and CARE-MS II trials. Those studies indicated that alemtuzumab improved clinical and MRI outcomes over 2 years in relapsing-remitting MS, compared with interferon beta-1a. In a 4-year extension, alemtuzumab’s efficacy was maintained, and 81% of participants continued in the study until year 6. In addition, 34% of alemtuzumab-treated patients in CARE-MS I and 43% of alemtuzumab-treated patients in CARE-MS II achieved 6-month confirmed disability improvement. The relationship between baseline disability levels and the achievement of disability improvement is not well understood, however.
Dr. Hunter and colleagues conducted a pooled analysis of CARE-MS I and CARE-MS II data to evaluate how baseline disability affects improvements in each functional system in patients treated with alemtuzumab over 6 years. In those studies, patients received two 12-mg/day courses of alemtuzumab: a 5-day course at baseline and a 3-day course 12 months later. Additional treatment with alemtuzumab or other disease-modifying therapies was provided as needed during the extension study.
The investigators defined confirmed disability improvement as a decrease of 1 or more points in EDSS score confirmed over 6 months among patients with a baseline EDSS score of 2 or higher. Improvement (i.e., a decrease of 1 or more points) or stability (i.e., no change) in each of the functional system scores was assessed in patients with confirmed disability improvement, stratified by baseline EDSS scores. Patients were grouped according to whether their baseline EDSS scores were 2.0-2.5, 3.0-3.5, 4.0-4.5, 5.0-5.5, or 6.0-6.5.
A total of 208 of 565 patients (37%) achieved 6-month confirmed disability improvement through year 6. This outcome was achieved by the highest percentages of patients with baseline EDSS scores of 4.0-4.5 (57%) and 3.0-3.5 (44%), followed by those with baseline EDSS scores of 5.0-5.5 (28%) and 2.0-2.5 (27%). No patients with baseline EDSS scores of 6.0-6.5 achieved confirmed disability improvement.
At 6 months after onset of confirmed disability improvement, patients within each baseline EDSS group showed stability or improvement in each individual functional system. The proportion of stable or improved patients was 94% or greater in the 2.0-2.5 group, 92% or greater in the 3.0-3.5 group, 88% or greater in the 4.0-4.5 group, and 75% or greater in the 5.0-5.5 group. Between 67% and 76% of patients achieved improvements in two or more functional systems. Improvements were most frequent in the pyramidal (13% to 50%), sensory (42% to 50%), and cerebellar (13% to 55%) functional systems.
Sanofi, Bayer HealthCare Pharmaceuticals supported the study. Dr. Hunter received grants and financial support from AbbVie, Actelion, Acorda, Adamas, Alkermes, Avanir, Bayer HealthCare, Biogen, Novartis, Osmotica, Questcor, Roche, Sanofi, Synthon, and Teva.
SOURCE: Hunter SF et al. CMSC 2019. Abstract DXT08.
Seattle – , according to a pooled analysis presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Patients who achieved this outcome had improvement in several functional systems, regardless of their baseline EDSS scores. “These results suggest a broad and prolonged effect of alemtuzumab on disability improvement and a potential for changing the MS disease course,” said Samuel F. Hunter, MD, a neurologist and psychiatrist at the Advanced Neurosciences Institute in Franklin, Tenn., and colleagues.
The researchers’ findings come from their analysis of pooled data from the CARE-MS I and CARE-MS II trials. Those studies indicated that alemtuzumab improved clinical and MRI outcomes over 2 years in relapsing-remitting MS, compared with interferon beta-1a. In a 4-year extension, alemtuzumab’s efficacy was maintained, and 81% of participants continued in the study until year 6. In addition, 34% of alemtuzumab-treated patients in CARE-MS I and 43% of alemtuzumab-treated patients in CARE-MS II achieved 6-month confirmed disability improvement. The relationship between baseline disability levels and the achievement of disability improvement is not well understood, however.
Dr. Hunter and colleagues conducted a pooled analysis of CARE-MS I and CARE-MS II data to evaluate how baseline disability affects improvements in each functional system in patients treated with alemtuzumab over 6 years. In those studies, patients received two 12-mg/day courses of alemtuzumab: a 5-day course at baseline and a 3-day course 12 months later. Additional treatment with alemtuzumab or other disease-modifying therapies was provided as needed during the extension study.
The investigators defined confirmed disability improvement as a decrease of 1 or more points in EDSS score confirmed over 6 months among patients with a baseline EDSS score of 2 or higher. Improvement (i.e., a decrease of 1 or more points) or stability (i.e., no change) in each of the functional system scores was assessed in patients with confirmed disability improvement, stratified by baseline EDSS scores. Patients were grouped according to whether their baseline EDSS scores were 2.0-2.5, 3.0-3.5, 4.0-4.5, 5.0-5.5, or 6.0-6.5.
A total of 208 of 565 patients (37%) achieved 6-month confirmed disability improvement through year 6. This outcome was achieved by the highest percentages of patients with baseline EDSS scores of 4.0-4.5 (57%) and 3.0-3.5 (44%), followed by those with baseline EDSS scores of 5.0-5.5 (28%) and 2.0-2.5 (27%). No patients with baseline EDSS scores of 6.0-6.5 achieved confirmed disability improvement.
At 6 months after onset of confirmed disability improvement, patients within each baseline EDSS group showed stability or improvement in each individual functional system. The proportion of stable or improved patients was 94% or greater in the 2.0-2.5 group, 92% or greater in the 3.0-3.5 group, 88% or greater in the 4.0-4.5 group, and 75% or greater in the 5.0-5.5 group. Between 67% and 76% of patients achieved improvements in two or more functional systems. Improvements were most frequent in the pyramidal (13% to 50%), sensory (42% to 50%), and cerebellar (13% to 55%) functional systems.
Sanofi, Bayer HealthCare Pharmaceuticals supported the study. Dr. Hunter received grants and financial support from AbbVie, Actelion, Acorda, Adamas, Alkermes, Avanir, Bayer HealthCare, Biogen, Novartis, Osmotica, Questcor, Roche, Sanofi, Synthon, and Teva.
SOURCE: Hunter SF et al. CMSC 2019. Abstract DXT08.
REPORTING FROM CMSC 2019
Evobrutinib demonstrates efficacy, safety in relapsing MS
PHILADELPHIA – Higher doses of evobrutinib significantly improved that study endpoint, and were associated with numerical decreases in the annualized relapse rate versus placebo, according to a report presented at the annual meeting of the American Academy of Neurology.
Some grade 3-4 transaminase elevations were associated with evobrutinib, though these were asymptomatic, reversible, and occurred within the first 24 weeks of the 48-week treatment period, said investigator Xavier Montalban, MD, PhD, chairman and director of the department of neurology-neuroimmunology at Vall d’Hebron University Hospital in Barcelona.
“Overall, we do believe the results of the phase 2 study support further clinical development in relapsing multiple sclerosis,” Dr. Montalban said.
This study builds on previous observations that BTK plays an important role in immune functions related to the pathogenesis of MS, Dr. Montalban said. Evobrutinib in particular impacts B cells and myeloid cells along with pathways involved in MS-related inflammation, he added.
In the current randomized, phase 2, placebo-controlled study, 267 patients with relapsing MS were randomized to one of five arms: placebo, evobrutinib 25-mg daily, 75-mg daily, or 75-mg twice daily, or an open-label reference arm of dimethyl fumarate 240 mg twice daily.
Dr. Montalban presented the results of a 24-week treatment period plus a 24-week blinded extension period, during which placebo-treated patients crossed over to evobrutinib 25 mg daily, for a total of 48 weeks of treatment.
The primary study endpoint was the cumulative number of MRI-assessed T1 Gd+ lesions at weeks 12, 16, 20, and 24. Dr. Montalban said that evobrutinib in the two 75-mg arms significantly reduced enhancing lesions versus placebo over weeks 12-24, with lesion rate ratios of 0.30 for the 75-mg daily arm, and 0.44 for the 75-mg twice-daily arm, with unadjusted P values of .002 and .031, respectively. By contrast, the evobrutinib 25-mg arm did not significantly reduce the cumulative number of enhancing lesions versus placebo over that time period.
There was a rapid reduction in the mean number of enhancing lesions from baseline to the week-12 visit for those 75-mg dosing arms, which was sustained through subsequent visits, Dr. Montalban said.
There were no significant differences between arms in the annualized relapse rate at week 24, a key secondary endpoint of the study, according to the investigators. The annualized relapse rate was 0.37 for placebo, 0.57 for evobrutinib 25 mg daily, 0.13 for the 75-mg daily dose, 0.08 for the 75-mg twice-daily dose, and 0.20 for dimethyl fumarate. The magnitude of reduction was maintained at the 48-week evaluation for evobrutinib 75 mg twice daily, with an annualized relapse rate of 0.11, Dr. Montalban reported.
Most treatment-emergent adverse events were mild or moderate, according to the investigators.
Reported ALT elevations in the evobrutinib arms were mainly grade 1. While some grade 3-4 elevations were seen in the first 24 weeks of the study, they were reversible and did not have clinical consequences, according to Dr. Montalban.
Results of the study were published concurrently in the New England Journal of Medicine.
Dr. Montalban provided disclosures related to Biogen, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche, Celgene, Actelion, National Multiple Sclerosis Society, and Multiple Sclerosis International Federation.
SOURCE: Montalban X et al. AAN 2019. Abstract S56.004.
PHILADELPHIA – Higher doses of evobrutinib significantly improved that study endpoint, and were associated with numerical decreases in the annualized relapse rate versus placebo, according to a report presented at the annual meeting of the American Academy of Neurology.
Some grade 3-4 transaminase elevations were associated with evobrutinib, though these were asymptomatic, reversible, and occurred within the first 24 weeks of the 48-week treatment period, said investigator Xavier Montalban, MD, PhD, chairman and director of the department of neurology-neuroimmunology at Vall d’Hebron University Hospital in Barcelona.
“Overall, we do believe the results of the phase 2 study support further clinical development in relapsing multiple sclerosis,” Dr. Montalban said.
This study builds on previous observations that BTK plays an important role in immune functions related to the pathogenesis of MS, Dr. Montalban said. Evobrutinib in particular impacts B cells and myeloid cells along with pathways involved in MS-related inflammation, he added.
In the current randomized, phase 2, placebo-controlled study, 267 patients with relapsing MS were randomized to one of five arms: placebo, evobrutinib 25-mg daily, 75-mg daily, or 75-mg twice daily, or an open-label reference arm of dimethyl fumarate 240 mg twice daily.
Dr. Montalban presented the results of a 24-week treatment period plus a 24-week blinded extension period, during which placebo-treated patients crossed over to evobrutinib 25 mg daily, for a total of 48 weeks of treatment.
The primary study endpoint was the cumulative number of MRI-assessed T1 Gd+ lesions at weeks 12, 16, 20, and 24. Dr. Montalban said that evobrutinib in the two 75-mg arms significantly reduced enhancing lesions versus placebo over weeks 12-24, with lesion rate ratios of 0.30 for the 75-mg daily arm, and 0.44 for the 75-mg twice-daily arm, with unadjusted P values of .002 and .031, respectively. By contrast, the evobrutinib 25-mg arm did not significantly reduce the cumulative number of enhancing lesions versus placebo over that time period.
There was a rapid reduction in the mean number of enhancing lesions from baseline to the week-12 visit for those 75-mg dosing arms, which was sustained through subsequent visits, Dr. Montalban said.
There were no significant differences between arms in the annualized relapse rate at week 24, a key secondary endpoint of the study, according to the investigators. The annualized relapse rate was 0.37 for placebo, 0.57 for evobrutinib 25 mg daily, 0.13 for the 75-mg daily dose, 0.08 for the 75-mg twice-daily dose, and 0.20 for dimethyl fumarate. The magnitude of reduction was maintained at the 48-week evaluation for evobrutinib 75 mg twice daily, with an annualized relapse rate of 0.11, Dr. Montalban reported.
Most treatment-emergent adverse events were mild or moderate, according to the investigators.
Reported ALT elevations in the evobrutinib arms were mainly grade 1. While some grade 3-4 elevations were seen in the first 24 weeks of the study, they were reversible and did not have clinical consequences, according to Dr. Montalban.
Results of the study were published concurrently in the New England Journal of Medicine.
Dr. Montalban provided disclosures related to Biogen, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche, Celgene, Actelion, National Multiple Sclerosis Society, and Multiple Sclerosis International Federation.
SOURCE: Montalban X et al. AAN 2019. Abstract S56.004.
PHILADELPHIA – Higher doses of evobrutinib significantly improved that study endpoint, and were associated with numerical decreases in the annualized relapse rate versus placebo, according to a report presented at the annual meeting of the American Academy of Neurology.
Some grade 3-4 transaminase elevations were associated with evobrutinib, though these were asymptomatic, reversible, and occurred within the first 24 weeks of the 48-week treatment period, said investigator Xavier Montalban, MD, PhD, chairman and director of the department of neurology-neuroimmunology at Vall d’Hebron University Hospital in Barcelona.
“Overall, we do believe the results of the phase 2 study support further clinical development in relapsing multiple sclerosis,” Dr. Montalban said.
This study builds on previous observations that BTK plays an important role in immune functions related to the pathogenesis of MS, Dr. Montalban said. Evobrutinib in particular impacts B cells and myeloid cells along with pathways involved in MS-related inflammation, he added.
In the current randomized, phase 2, placebo-controlled study, 267 patients with relapsing MS were randomized to one of five arms: placebo, evobrutinib 25-mg daily, 75-mg daily, or 75-mg twice daily, or an open-label reference arm of dimethyl fumarate 240 mg twice daily.
Dr. Montalban presented the results of a 24-week treatment period plus a 24-week blinded extension period, during which placebo-treated patients crossed over to evobrutinib 25 mg daily, for a total of 48 weeks of treatment.
The primary study endpoint was the cumulative number of MRI-assessed T1 Gd+ lesions at weeks 12, 16, 20, and 24. Dr. Montalban said that evobrutinib in the two 75-mg arms significantly reduced enhancing lesions versus placebo over weeks 12-24, with lesion rate ratios of 0.30 for the 75-mg daily arm, and 0.44 for the 75-mg twice-daily arm, with unadjusted P values of .002 and .031, respectively. By contrast, the evobrutinib 25-mg arm did not significantly reduce the cumulative number of enhancing lesions versus placebo over that time period.
There was a rapid reduction in the mean number of enhancing lesions from baseline to the week-12 visit for those 75-mg dosing arms, which was sustained through subsequent visits, Dr. Montalban said.
There were no significant differences between arms in the annualized relapse rate at week 24, a key secondary endpoint of the study, according to the investigators. The annualized relapse rate was 0.37 for placebo, 0.57 for evobrutinib 25 mg daily, 0.13 for the 75-mg daily dose, 0.08 for the 75-mg twice-daily dose, and 0.20 for dimethyl fumarate. The magnitude of reduction was maintained at the 48-week evaluation for evobrutinib 75 mg twice daily, with an annualized relapse rate of 0.11, Dr. Montalban reported.
Most treatment-emergent adverse events were mild or moderate, according to the investigators.
Reported ALT elevations in the evobrutinib arms were mainly grade 1. While some grade 3-4 elevations were seen in the first 24 weeks of the study, they were reversible and did not have clinical consequences, according to Dr. Montalban.
Results of the study were published concurrently in the New England Journal of Medicine.
Dr. Montalban provided disclosures related to Biogen, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, Roche, Celgene, Actelion, National Multiple Sclerosis Society, and Multiple Sclerosis International Federation.
SOURCE: Montalban X et al. AAN 2019. Abstract S56.004.
FROM AAN 2019
Fingolimod reduced disease activity more than glatiramer acetate in RRMS: ASSESS study results
PHILADELPHIA – reported at the annual meeting of the American Academy of Neurology. The optimal efficacious dose of fingolimod was 0.5 mg once daily, according to the results of the ASSESS study, which also evaluated a 0.25-mg daily dose of fingolimod versus a 20-mg daily dose of glatiramer acetate.
Adverse events seen with fingolimod were consistent with the established safety profile of the immunomodulatory drug, according to investigator Bruce Cree, MD, PhD, of the UCSF Weill Institute for Neurosciences, department of neurology, University of California, San Francisco.
“I believe this is the first study to go head to head versus glatiramer acetate to show superiority,” Dr. Cree said in a podium presentation of the results.
While fingolimod 0.5 mg has shown superior efficacy over placebo and interferon beta-1a in previous phase 3 trials, head-to-head comparisons versus disease-modifying therapies can help inform treatment decisions in clinical practice, Dr. Cree and coinvestigators noted in the abstract that describes their results.
The randomized, three-armed, phase 3b ASSESS study included 12 months of dose-blinded treatment and 3 months of follow-up. Investigators enrolled 1,054 patients with relapsing-remitting MS, of whom about 74% were women and the average age was 40 years, Dr. Cree said in his presentation.
Annualized relapse rate, the primary endpoint of the study, was 0.153 for the fingolimod 0.5-mg arm, versus 0.258 for the glatiramer acetate 20-mg arm, for a 40.7% relative reduction (P = .013), Dr. Cree reported. By contrast, he said, the annualized relapse rate within the fingolimod 0.25-mg arm was 0.221, which was not statistically different versus glatiramer acetate.
The fingolimod 0.5-mg arm was also superior to glatiramer acetate on a number of radiographic endpoints at month 12, including new or newly enlarged T2 lesion count, change in T2 lesion volume, gadolinium-positive T1 lesion count, and gadolinium-positive T1 lesion volume, Dr. Cree said.
Adverse events and serious adverse events were “much as expected” in all three study groups, Dr. Cree said.
The observed safety with fingolimod was consistent with previously available data on fingolimod 0.5 mg, and the safety profile of the lower 0.25-mg dose seemed to be comparable with the 0.5-mg dose, according to his presentation.
Adverse events with fingolimod were “largely laboratory abnormalities,” that occurred more frequently in the fingolimod arms, he said. Although there was an apparent dose-dependent effect between the 0.25-mg and 0.5-mg doses, the overall proportion of patients experiencing low white blood cell counts or elevations in liver enzymes was low, he added.
Bradycardia was “infrequent” in both fingolimod groups in first-dose observations, though it did again occur with a dose-dependent effect, Dr. Cree said.
He reported bradycardia in two patients (0.5%) in the fingolimod 0.25-mg group and four (1.2%) in the fingolimod 0.5-mg group, while the number of patients requiring overnight hospitalizations was one (0.3%) and five (1.5%) in the 0.25- and 0.5-mg groups, respectively.
Hepatic enzyme abnormalities were the leading reason for discontinuation of fingolimod, while in contrast, drug hypersensitivity and injection site reactions led to discontinuations in the glatiramer acetate arm, he added.
Novartis sponsored the study. Dr. Cree provided disclosures related to Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.
SOURCE: Cree B et al. AAN 2019, Abstract 56.009.
PHILADELPHIA – reported at the annual meeting of the American Academy of Neurology. The optimal efficacious dose of fingolimod was 0.5 mg once daily, according to the results of the ASSESS study, which also evaluated a 0.25-mg daily dose of fingolimod versus a 20-mg daily dose of glatiramer acetate.
Adverse events seen with fingolimod were consistent with the established safety profile of the immunomodulatory drug, according to investigator Bruce Cree, MD, PhD, of the UCSF Weill Institute for Neurosciences, department of neurology, University of California, San Francisco.
“I believe this is the first study to go head to head versus glatiramer acetate to show superiority,” Dr. Cree said in a podium presentation of the results.
While fingolimod 0.5 mg has shown superior efficacy over placebo and interferon beta-1a in previous phase 3 trials, head-to-head comparisons versus disease-modifying therapies can help inform treatment decisions in clinical practice, Dr. Cree and coinvestigators noted in the abstract that describes their results.
The randomized, three-armed, phase 3b ASSESS study included 12 months of dose-blinded treatment and 3 months of follow-up. Investigators enrolled 1,054 patients with relapsing-remitting MS, of whom about 74% were women and the average age was 40 years, Dr. Cree said in his presentation.
Annualized relapse rate, the primary endpoint of the study, was 0.153 for the fingolimod 0.5-mg arm, versus 0.258 for the glatiramer acetate 20-mg arm, for a 40.7% relative reduction (P = .013), Dr. Cree reported. By contrast, he said, the annualized relapse rate within the fingolimod 0.25-mg arm was 0.221, which was not statistically different versus glatiramer acetate.
The fingolimod 0.5-mg arm was also superior to glatiramer acetate on a number of radiographic endpoints at month 12, including new or newly enlarged T2 lesion count, change in T2 lesion volume, gadolinium-positive T1 lesion count, and gadolinium-positive T1 lesion volume, Dr. Cree said.
Adverse events and serious adverse events were “much as expected” in all three study groups, Dr. Cree said.
The observed safety with fingolimod was consistent with previously available data on fingolimod 0.5 mg, and the safety profile of the lower 0.25-mg dose seemed to be comparable with the 0.5-mg dose, according to his presentation.
Adverse events with fingolimod were “largely laboratory abnormalities,” that occurred more frequently in the fingolimod arms, he said. Although there was an apparent dose-dependent effect between the 0.25-mg and 0.5-mg doses, the overall proportion of patients experiencing low white blood cell counts or elevations in liver enzymes was low, he added.
Bradycardia was “infrequent” in both fingolimod groups in first-dose observations, though it did again occur with a dose-dependent effect, Dr. Cree said.
He reported bradycardia in two patients (0.5%) in the fingolimod 0.25-mg group and four (1.2%) in the fingolimod 0.5-mg group, while the number of patients requiring overnight hospitalizations was one (0.3%) and five (1.5%) in the 0.25- and 0.5-mg groups, respectively.
Hepatic enzyme abnormalities were the leading reason for discontinuation of fingolimod, while in contrast, drug hypersensitivity and injection site reactions led to discontinuations in the glatiramer acetate arm, he added.
Novartis sponsored the study. Dr. Cree provided disclosures related to Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.
SOURCE: Cree B et al. AAN 2019, Abstract 56.009.
PHILADELPHIA – reported at the annual meeting of the American Academy of Neurology. The optimal efficacious dose of fingolimod was 0.5 mg once daily, according to the results of the ASSESS study, which also evaluated a 0.25-mg daily dose of fingolimod versus a 20-mg daily dose of glatiramer acetate.
Adverse events seen with fingolimod were consistent with the established safety profile of the immunomodulatory drug, according to investigator Bruce Cree, MD, PhD, of the UCSF Weill Institute for Neurosciences, department of neurology, University of California, San Francisco.
“I believe this is the first study to go head to head versus glatiramer acetate to show superiority,” Dr. Cree said in a podium presentation of the results.
While fingolimod 0.5 mg has shown superior efficacy over placebo and interferon beta-1a in previous phase 3 trials, head-to-head comparisons versus disease-modifying therapies can help inform treatment decisions in clinical practice, Dr. Cree and coinvestigators noted in the abstract that describes their results.
The randomized, three-armed, phase 3b ASSESS study included 12 months of dose-blinded treatment and 3 months of follow-up. Investigators enrolled 1,054 patients with relapsing-remitting MS, of whom about 74% were women and the average age was 40 years, Dr. Cree said in his presentation.
Annualized relapse rate, the primary endpoint of the study, was 0.153 for the fingolimod 0.5-mg arm, versus 0.258 for the glatiramer acetate 20-mg arm, for a 40.7% relative reduction (P = .013), Dr. Cree reported. By contrast, he said, the annualized relapse rate within the fingolimod 0.25-mg arm was 0.221, which was not statistically different versus glatiramer acetate.
The fingolimod 0.5-mg arm was also superior to glatiramer acetate on a number of radiographic endpoints at month 12, including new or newly enlarged T2 lesion count, change in T2 lesion volume, gadolinium-positive T1 lesion count, and gadolinium-positive T1 lesion volume, Dr. Cree said.
Adverse events and serious adverse events were “much as expected” in all three study groups, Dr. Cree said.
The observed safety with fingolimod was consistent with previously available data on fingolimod 0.5 mg, and the safety profile of the lower 0.25-mg dose seemed to be comparable with the 0.5-mg dose, according to his presentation.
Adverse events with fingolimod were “largely laboratory abnormalities,” that occurred more frequently in the fingolimod arms, he said. Although there was an apparent dose-dependent effect between the 0.25-mg and 0.5-mg doses, the overall proportion of patients experiencing low white blood cell counts or elevations in liver enzymes was low, he added.
Bradycardia was “infrequent” in both fingolimod groups in first-dose observations, though it did again occur with a dose-dependent effect, Dr. Cree said.
He reported bradycardia in two patients (0.5%) in the fingolimod 0.25-mg group and four (1.2%) in the fingolimod 0.5-mg group, while the number of patients requiring overnight hospitalizations was one (0.3%) and five (1.5%) in the 0.25- and 0.5-mg groups, respectively.
Hepatic enzyme abnormalities were the leading reason for discontinuation of fingolimod, while in contrast, drug hypersensitivity and injection site reactions led to discontinuations in the glatiramer acetate arm, he added.
Novartis sponsored the study. Dr. Cree provided disclosures related to Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.
SOURCE: Cree B et al. AAN 2019, Abstract 56.009.
REPORTING FROM AAN 2019
Sugary drink intake may be associated with MS severity
PHILADELPHIA – presented at the annual meeting of the American Academy of Neurology. Overall diet quality, however, is not associated with disability, the study showed.
The results do not establish that sugary drinks cause disability, and the potential association needs to be confirmed in larger, longitudinal studies, the researchers said. Nevertheless, “we do know that sodas have no nutritional value, and people with MS may want to consider reducing or eliminating them from their diet,” study lead author Elisa Meier-Gerdingh, MD, of St. Josef Hospital in Bochum, Germany, said in a written statement.
Diet may influence metabolic comorbidities, immune function, oxidative stress, and gut microbiota in patients with MS, but data about diet’s effects on MS progression are limited, the researchers said.
To examine dietary intake and disability in patients with MS, Dr. Meier-Gerdingh and her colleagues conducted a cross-sectional study of 135 participants with MS who were treated at a large referral center in Germany. Participants had a mean age of 44.6 years and mean body mass index of 24.5. Mean disease duration was 13.8 years, and 73% were women. Participants completed a 102-item food frequency questionnaire, which the investigators used to calculate each participant’s Dietary Approaches to Stop Hypertension (DASH) score. The score is a composite measure of dietary quality that favorably scores intake of fruits, vegetables, nuts and legumes, whole grains, and dairy and unfavorably scores intake of sodium, sugar-sweetened beverages, and red and processed meats.
“We chose to study the DASH diet because adherence to the DASH diet is associated with lower risk of other chronic diseases like high blood pressure, diabetes, and cardiovascular diseases,” Dr. Meier-Gerdingh said.
The researchers considered severe disability to be an Expanded Disability Status Scale (EDSS) score of 6 or greater. They assessed the association between overall DASH scores and disability status using logistic regression models that adjusted for age, sex, body mass index, smoking, and symptom duration. They also assessed the association between disability and each nutritional component of the DASH score.
In all, 30 participants had severe disability. “Overall DASH scores were not associated with disability status,” Dr. Meier-Gerdingh and her colleagues said. When they looked at individual DASH score components, patients with higher intakes of sugar-sweetened beverages had a higher risk of severe disability (P for trend = .01). Participants in the highest quartile consumed about 290 calories of sugar-sweetened beverages per day on average, compared with 7 calories per day for patients in the lowest quartile. The top quartile had an average EDSS of 4.1, and the bottom quartile had an average EDSS of 3.4. Other DASH score components were not associated with disability status.
Dr. Meier-Gerdingh had no disclosures. Her coauthors reported research support and personal compensation from pharmaceutical companies.
SOURCE: Meier-Gerdingh E et al. AAN 2019, Abstract P4.2-063.
PHILADELPHIA – presented at the annual meeting of the American Academy of Neurology. Overall diet quality, however, is not associated with disability, the study showed.
The results do not establish that sugary drinks cause disability, and the potential association needs to be confirmed in larger, longitudinal studies, the researchers said. Nevertheless, “we do know that sodas have no nutritional value, and people with MS may want to consider reducing or eliminating them from their diet,” study lead author Elisa Meier-Gerdingh, MD, of St. Josef Hospital in Bochum, Germany, said in a written statement.
Diet may influence metabolic comorbidities, immune function, oxidative stress, and gut microbiota in patients with MS, but data about diet’s effects on MS progression are limited, the researchers said.
To examine dietary intake and disability in patients with MS, Dr. Meier-Gerdingh and her colleagues conducted a cross-sectional study of 135 participants with MS who were treated at a large referral center in Germany. Participants had a mean age of 44.6 years and mean body mass index of 24.5. Mean disease duration was 13.8 years, and 73% were women. Participants completed a 102-item food frequency questionnaire, which the investigators used to calculate each participant’s Dietary Approaches to Stop Hypertension (DASH) score. The score is a composite measure of dietary quality that favorably scores intake of fruits, vegetables, nuts and legumes, whole grains, and dairy and unfavorably scores intake of sodium, sugar-sweetened beverages, and red and processed meats.
“We chose to study the DASH diet because adherence to the DASH diet is associated with lower risk of other chronic diseases like high blood pressure, diabetes, and cardiovascular diseases,” Dr. Meier-Gerdingh said.
The researchers considered severe disability to be an Expanded Disability Status Scale (EDSS) score of 6 or greater. They assessed the association between overall DASH scores and disability status using logistic regression models that adjusted for age, sex, body mass index, smoking, and symptom duration. They also assessed the association between disability and each nutritional component of the DASH score.
In all, 30 participants had severe disability. “Overall DASH scores were not associated with disability status,” Dr. Meier-Gerdingh and her colleagues said. When they looked at individual DASH score components, patients with higher intakes of sugar-sweetened beverages had a higher risk of severe disability (P for trend = .01). Participants in the highest quartile consumed about 290 calories of sugar-sweetened beverages per day on average, compared with 7 calories per day for patients in the lowest quartile. The top quartile had an average EDSS of 4.1, and the bottom quartile had an average EDSS of 3.4. Other DASH score components were not associated with disability status.
Dr. Meier-Gerdingh had no disclosures. Her coauthors reported research support and personal compensation from pharmaceutical companies.
SOURCE: Meier-Gerdingh E et al. AAN 2019, Abstract P4.2-063.
PHILADELPHIA – presented at the annual meeting of the American Academy of Neurology. Overall diet quality, however, is not associated with disability, the study showed.
The results do not establish that sugary drinks cause disability, and the potential association needs to be confirmed in larger, longitudinal studies, the researchers said. Nevertheless, “we do know that sodas have no nutritional value, and people with MS may want to consider reducing or eliminating them from their diet,” study lead author Elisa Meier-Gerdingh, MD, of St. Josef Hospital in Bochum, Germany, said in a written statement.
Diet may influence metabolic comorbidities, immune function, oxidative stress, and gut microbiota in patients with MS, but data about diet’s effects on MS progression are limited, the researchers said.
To examine dietary intake and disability in patients with MS, Dr. Meier-Gerdingh and her colleagues conducted a cross-sectional study of 135 participants with MS who were treated at a large referral center in Germany. Participants had a mean age of 44.6 years and mean body mass index of 24.5. Mean disease duration was 13.8 years, and 73% were women. Participants completed a 102-item food frequency questionnaire, which the investigators used to calculate each participant’s Dietary Approaches to Stop Hypertension (DASH) score. The score is a composite measure of dietary quality that favorably scores intake of fruits, vegetables, nuts and legumes, whole grains, and dairy and unfavorably scores intake of sodium, sugar-sweetened beverages, and red and processed meats.
“We chose to study the DASH diet because adherence to the DASH diet is associated with lower risk of other chronic diseases like high blood pressure, diabetes, and cardiovascular diseases,” Dr. Meier-Gerdingh said.
The researchers considered severe disability to be an Expanded Disability Status Scale (EDSS) score of 6 or greater. They assessed the association between overall DASH scores and disability status using logistic regression models that adjusted for age, sex, body mass index, smoking, and symptom duration. They also assessed the association between disability and each nutritional component of the DASH score.
In all, 30 participants had severe disability. “Overall DASH scores were not associated with disability status,” Dr. Meier-Gerdingh and her colleagues said. When they looked at individual DASH score components, patients with higher intakes of sugar-sweetened beverages had a higher risk of severe disability (P for trend = .01). Participants in the highest quartile consumed about 290 calories of sugar-sweetened beverages per day on average, compared with 7 calories per day for patients in the lowest quartile. The top quartile had an average EDSS of 4.1, and the bottom quartile had an average EDSS of 3.4. Other DASH score components were not associated with disability status.
Dr. Meier-Gerdingh had no disclosures. Her coauthors reported research support and personal compensation from pharmaceutical companies.
SOURCE: Meier-Gerdingh E et al. AAN 2019, Abstract P4.2-063.
REPORTING FROM AAN 2019
BTK inhibitor reduces MS enhancing lesions
. However, there was no difference between the 25-mg once daily, 75-mg once daily, 75-mg twice daily, and placebo-treated groups in Expanded Disability Status Scale scores, according to a double-blind, randomized, phase 2 trial published in the New England Journal of Medicine (2019 May 10. doi: 10.1056/NEJMoa1901981).
We first reported on the results of this trial when they were presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Find our coverage at the link below.
. However, there was no difference between the 25-mg once daily, 75-mg once daily, 75-mg twice daily, and placebo-treated groups in Expanded Disability Status Scale scores, according to a double-blind, randomized, phase 2 trial published in the New England Journal of Medicine (2019 May 10. doi: 10.1056/NEJMoa1901981).
We first reported on the results of this trial when they were presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Find our coverage at the link below.
. However, there was no difference between the 25-mg once daily, 75-mg once daily, 75-mg twice daily, and placebo-treated groups in Expanded Disability Status Scale scores, according to a double-blind, randomized, phase 2 trial published in the New England Journal of Medicine (2019 May 10. doi: 10.1056/NEJMoa1901981).
We first reported on the results of this trial when they were presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. Find our coverage at the link below.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Changes in brain networks may predict MS worsening
PHILADELPHIA – (MS), according to a study described at the annual meeting of the American Academy of Neurology.
Neurologists do not have reliable biomarkers to predict disease evolution in the medium or long term for patients with MS. The ability to predict disease evolution accurately could aid in the choice of treatment.
Maria Assunta Rocca, MD, head of the Neuroimaging of CNS White Matter Unit, Department of Neurology, Institute of Experimental Neurology, Scientific Institute Ospedale, San Raffaele, Milan, Italy, and colleagues sought to evaluate structural and functional network MRI measures as predictors of clinical deterioration over 6.5 years. They obtained conventional, 3D, T1-weighted, diffusion-weighted MRI, and resting-state functional MRI images at baseline from 233 patients with MS and 77 healthy controls. Patients underwent a neurologic examination at baseline and after a median follow-up period of 6.5 years. At follow-up, the researchers classified patients as clinically stable or worsened, according to their change in Expanded Disability Status Scale (EDSS) score. They also evaluated conversion to secondary progressive MS among patients with relapsing remitting MS at baseline.
To identify the main large-scale resting state functional connectivity networks, Dr. Rocca and colleagues applied spatial independent component analysis to resting state functional MRI data. They applied the same technique to gray matter probability maps and fractional anisotropy maps to identify the corresponding structural gray matter and white matter networks.
At follow-up, 105 patients with MS (45%) had significant EDSS worsening. Of 157 patients with relapsing remitting MS, 26 (16%) converted to secondary progressive MS. The multivariable model, after adjustment for follow-up duration, identified baseline EDSS score (odds ratio, 1.59), normalized gray matter volume (OR, 0.99), and abnormally high baseline resting state functional connectivity of the left precentral gyrus in the sensorimotor network (OR, 1.67) as predictors of EDSS worsening. These variables remained significant after the researchers adjusted for treatment effect. Independent variables associated with conversion to secondary progressive MS included baseline EDSS score (OR, 2.8) and atrophy of gray matter networks associated with sensory (OR, 0.5) and motor (OR, 0.4) functions.
Dr. Rocca received personal compensation from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche. Coauthors reported research support from Biogen, Merck Serono, Novartis, Teva, and Roche..
SOURCE: Filippi M et al. AAN 2019, Abstract S49.004.
PHILADELPHIA – (MS), according to a study described at the annual meeting of the American Academy of Neurology.
Neurologists do not have reliable biomarkers to predict disease evolution in the medium or long term for patients with MS. The ability to predict disease evolution accurately could aid in the choice of treatment.
Maria Assunta Rocca, MD, head of the Neuroimaging of CNS White Matter Unit, Department of Neurology, Institute of Experimental Neurology, Scientific Institute Ospedale, San Raffaele, Milan, Italy, and colleagues sought to evaluate structural and functional network MRI measures as predictors of clinical deterioration over 6.5 years. They obtained conventional, 3D, T1-weighted, diffusion-weighted MRI, and resting-state functional MRI images at baseline from 233 patients with MS and 77 healthy controls. Patients underwent a neurologic examination at baseline and after a median follow-up period of 6.5 years. At follow-up, the researchers classified patients as clinically stable or worsened, according to their change in Expanded Disability Status Scale (EDSS) score. They also evaluated conversion to secondary progressive MS among patients with relapsing remitting MS at baseline.
To identify the main large-scale resting state functional connectivity networks, Dr. Rocca and colleagues applied spatial independent component analysis to resting state functional MRI data. They applied the same technique to gray matter probability maps and fractional anisotropy maps to identify the corresponding structural gray matter and white matter networks.
At follow-up, 105 patients with MS (45%) had significant EDSS worsening. Of 157 patients with relapsing remitting MS, 26 (16%) converted to secondary progressive MS. The multivariable model, after adjustment for follow-up duration, identified baseline EDSS score (odds ratio, 1.59), normalized gray matter volume (OR, 0.99), and abnormally high baseline resting state functional connectivity of the left precentral gyrus in the sensorimotor network (OR, 1.67) as predictors of EDSS worsening. These variables remained significant after the researchers adjusted for treatment effect. Independent variables associated with conversion to secondary progressive MS included baseline EDSS score (OR, 2.8) and atrophy of gray matter networks associated with sensory (OR, 0.5) and motor (OR, 0.4) functions.
Dr. Rocca received personal compensation from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche. Coauthors reported research support from Biogen, Merck Serono, Novartis, Teva, and Roche..
SOURCE: Filippi M et al. AAN 2019, Abstract S49.004.
PHILADELPHIA – (MS), according to a study described at the annual meeting of the American Academy of Neurology.
Neurologists do not have reliable biomarkers to predict disease evolution in the medium or long term for patients with MS. The ability to predict disease evolution accurately could aid in the choice of treatment.
Maria Assunta Rocca, MD, head of the Neuroimaging of CNS White Matter Unit, Department of Neurology, Institute of Experimental Neurology, Scientific Institute Ospedale, San Raffaele, Milan, Italy, and colleagues sought to evaluate structural and functional network MRI measures as predictors of clinical deterioration over 6.5 years. They obtained conventional, 3D, T1-weighted, diffusion-weighted MRI, and resting-state functional MRI images at baseline from 233 patients with MS and 77 healthy controls. Patients underwent a neurologic examination at baseline and after a median follow-up period of 6.5 years. At follow-up, the researchers classified patients as clinically stable or worsened, according to their change in Expanded Disability Status Scale (EDSS) score. They also evaluated conversion to secondary progressive MS among patients with relapsing remitting MS at baseline.
To identify the main large-scale resting state functional connectivity networks, Dr. Rocca and colleagues applied spatial independent component analysis to resting state functional MRI data. They applied the same technique to gray matter probability maps and fractional anisotropy maps to identify the corresponding structural gray matter and white matter networks.
At follow-up, 105 patients with MS (45%) had significant EDSS worsening. Of 157 patients with relapsing remitting MS, 26 (16%) converted to secondary progressive MS. The multivariable model, after adjustment for follow-up duration, identified baseline EDSS score (odds ratio, 1.59), normalized gray matter volume (OR, 0.99), and abnormally high baseline resting state functional connectivity of the left precentral gyrus in the sensorimotor network (OR, 1.67) as predictors of EDSS worsening. These variables remained significant after the researchers adjusted for treatment effect. Independent variables associated with conversion to secondary progressive MS included baseline EDSS score (OR, 2.8) and atrophy of gray matter networks associated with sensory (OR, 0.5) and motor (OR, 0.4) functions.
Dr. Rocca received personal compensation from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche. Coauthors reported research support from Biogen, Merck Serono, Novartis, Teva, and Roche..
SOURCE: Filippi M et al. AAN 2019, Abstract S49.004.
REPORTING FROM AAN 2019
Key clinical point: Structural and functional network MRI measures predict long-term worsening in multiple sclerosis.
Major finding: The odds ratio of worsening for patients with abnormally high baseline resting state functional connectivity is 1.67.
Study details: A prospective imaging study of 233 patients with multiple sclerosis and 77 healthy controls.
Disclosures: Dr. Rocca received personal compensation from Biogen Idec, Novartis, Genzyme, Sanofi-Aventis, Teva, Merck Serono, and Roche. Coauthors reported research support from Biogen, Merck Serono, Novartis, Teva, and Roche.
Source: Filippi M et al. AAN 2019, Abstract S49.004.
Ibudilast’s efficacy differs in primary and secondary progressive MS
PHILADELPHIA – researchers reported at the annual meeting of the American Academy of Neurology.
The difference may be related to faster atrophy rates among patients with primary progressive MS who received placebo, compared with those with secondary progressive MS who received placebo.
The finding was surprising, said Andrew Goodman, MD, professor of neurology, chief of the neuroimmunology unit, and director of the multiple sclerosis center at the University of Rochester (N.Y.). “Going into the trial, it was my bias and expectation that both primary and secondary progressive MS would behave more similarly than different.”
The trial, SPRINT-MS, included more than 250 patients with progressive MS at 28 sites. Patients were aged 18-65 years and were followed for 96 weeks. Patients had primary progressive MS (n = 134) or secondary progressive MS (n = 121) and were randomized 1:1 to ibudilast or placebo.
Ibudilast is an orally administered small molecule that has been used in Japan for approximately 30 years for asthma and other indications, Dr. Goodman said. Preclinical models suggested that the drug may have neuroprotective effects.
The trial’s primary result – a 48% slowing in the rate of whole brain atrophy as measured by brain parenchymal fraction with ibudilast – was reported last year (N Engl J Med. 2018 Aug 30;379[9]:846-55).
The present study examined whether the treatment effect of ibudilast was similar by progressive disease type using a linear mixed model analytic approach.
The group with primary progressive MS included a smaller percentage of women. Patients with secondary progressive MS had longer disease duration and more brain atrophy at baseline.
“The overall benefit which we previously reported appears to be driven by subjects with primary progressive rather than secondary progressive MS,” Dr. Goodman said. Accounting for baseline covariates did not affect this result.
Among patients who received placebo, brain atrophy in those with secondary progressive MS was 57% slower than in those with primary progressive MS. The rate of atrophy for untreated patients with primary progressive MS “was roughly twice as fast as that in the secondary progressive MS group, which we think may explain in part the differential in efficacy,” Dr. Goodman said. “These findings may impact future trial design for progressive MS.”
The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.
SOURCE: Goodman A et al. AAN 2019, Abstract S12.007.
PHILADELPHIA – researchers reported at the annual meeting of the American Academy of Neurology.
The difference may be related to faster atrophy rates among patients with primary progressive MS who received placebo, compared with those with secondary progressive MS who received placebo.
The finding was surprising, said Andrew Goodman, MD, professor of neurology, chief of the neuroimmunology unit, and director of the multiple sclerosis center at the University of Rochester (N.Y.). “Going into the trial, it was my bias and expectation that both primary and secondary progressive MS would behave more similarly than different.”
The trial, SPRINT-MS, included more than 250 patients with progressive MS at 28 sites. Patients were aged 18-65 years and were followed for 96 weeks. Patients had primary progressive MS (n = 134) or secondary progressive MS (n = 121) and were randomized 1:1 to ibudilast or placebo.
Ibudilast is an orally administered small molecule that has been used in Japan for approximately 30 years for asthma and other indications, Dr. Goodman said. Preclinical models suggested that the drug may have neuroprotective effects.
The trial’s primary result – a 48% slowing in the rate of whole brain atrophy as measured by brain parenchymal fraction with ibudilast – was reported last year (N Engl J Med. 2018 Aug 30;379[9]:846-55).
The present study examined whether the treatment effect of ibudilast was similar by progressive disease type using a linear mixed model analytic approach.
The group with primary progressive MS included a smaller percentage of women. Patients with secondary progressive MS had longer disease duration and more brain atrophy at baseline.
“The overall benefit which we previously reported appears to be driven by subjects with primary progressive rather than secondary progressive MS,” Dr. Goodman said. Accounting for baseline covariates did not affect this result.
Among patients who received placebo, brain atrophy in those with secondary progressive MS was 57% slower than in those with primary progressive MS. The rate of atrophy for untreated patients with primary progressive MS “was roughly twice as fast as that in the secondary progressive MS group, which we think may explain in part the differential in efficacy,” Dr. Goodman said. “These findings may impact future trial design for progressive MS.”
The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.
SOURCE: Goodman A et al. AAN 2019, Abstract S12.007.
PHILADELPHIA – researchers reported at the annual meeting of the American Academy of Neurology.
The difference may be related to faster atrophy rates among patients with primary progressive MS who received placebo, compared with those with secondary progressive MS who received placebo.
The finding was surprising, said Andrew Goodman, MD, professor of neurology, chief of the neuroimmunology unit, and director of the multiple sclerosis center at the University of Rochester (N.Y.). “Going into the trial, it was my bias and expectation that both primary and secondary progressive MS would behave more similarly than different.”
The trial, SPRINT-MS, included more than 250 patients with progressive MS at 28 sites. Patients were aged 18-65 years and were followed for 96 weeks. Patients had primary progressive MS (n = 134) or secondary progressive MS (n = 121) and were randomized 1:1 to ibudilast or placebo.
Ibudilast is an orally administered small molecule that has been used in Japan for approximately 30 years for asthma and other indications, Dr. Goodman said. Preclinical models suggested that the drug may have neuroprotective effects.
The trial’s primary result – a 48% slowing in the rate of whole brain atrophy as measured by brain parenchymal fraction with ibudilast – was reported last year (N Engl J Med. 2018 Aug 30;379[9]:846-55).
The present study examined whether the treatment effect of ibudilast was similar by progressive disease type using a linear mixed model analytic approach.
The group with primary progressive MS included a smaller percentage of women. Patients with secondary progressive MS had longer disease duration and more brain atrophy at baseline.
“The overall benefit which we previously reported appears to be driven by subjects with primary progressive rather than secondary progressive MS,” Dr. Goodman said. Accounting for baseline covariates did not affect this result.
Among patients who received placebo, brain atrophy in those with secondary progressive MS was 57% slower than in those with primary progressive MS. The rate of atrophy for untreated patients with primary progressive MS “was roughly twice as fast as that in the secondary progressive MS group, which we think may explain in part the differential in efficacy,” Dr. Goodman said. “These findings may impact future trial design for progressive MS.”
The SPRINT-MS trial was funded by the National Institute of Neurological Disorders and Stroke. The National Multiple Sclerosis Society and MediciNova also supported the study. Dr. Goodman reported receiving research support from pharmaceutical companies, as well as personal compensation from companies for consulting, serving on a scientific advisory board, and speaking.
SOURCE: Goodman A et al. AAN 2019, Abstract S12.007.
REPORTING FROM AAN 2019