Erik Greb

Seattle – Periodic limb movements during sleep (PLMS) are common in patients with multiple sclerosis (MS) who report fatigue, according to a retrospective analysis described at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“PLMS may contribute to daytime sleepiness and should be recognized and potentially treated. The etiology of fatigue related to sleep problems in people with MS is multifactorial and not just due to obstructive sleep apnea,” said lead author Jared Srinivasan, clinical research coordinator at South Shore Neurologic Associates in East Northport, New York, and colleagues.

Fatigue is common in patients with MS and can be disabling. For many patients with MS, sleep apnea is the underlying cause of fatigue. PLMS – leg movements that usually occur at 20- to 40-second intervals during sleep – are not commonly reported in MS. These movements cause sleep fragmentation, increase the energy cost of sleep, and contribute to daytime somnolence. Patients with PLMS often are unaware that they have them and do not report related symptoms unless they are specifically questioned about them. Polysomnography (PSG) is an effective, objective method of evaluating a patient for PLMS, but previous studies of PLMS in patients with MS have been small.

Mr. Srinivasan and colleagues performed a retrospective analysis to investigate the incidence and degree of PLMS in people with MS who had reported fatigue, had not previously been diagnosed as having sleep apnea or PLMS, and agreed to undergo overnight PSG.

The investigators included 292 participants in their study. The population’s average age was 47.3 years. Approximately 81% of patients were female. About 41% of the population had a PLMS index (PLMS per hour) greater than 0. Of participants with PSG-identified PLMS, 10% had a PLMS index of 5-10, 5% had a PLMS index of 11-21, and 12% had a PLMS index greater than 21. About 38% of the population experienced arousal because of PLMS. Of patients with arousal, 34% had a PLMS arousal index (number of arousals per hour) between 0 and 5, 31% had PLMS arousal index of 5-20, 14% had a PLMS arousal index of 20-50, and 21% had a PLMS arousal index greater than 50.

The investigators did not receive financial support for this study and did not report disclosures.
 

[email protected]

SOURCE: Srinivasan J et al. CMSC 2019. Abstract QOL29.

Seattle – Periodic limb movements during sleep (PLMS) are common in patients with multiple sclerosis (MS) who report fatigue, according to a retrospective analysis described at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“PLMS may contribute to daytime sleepiness and should be recognized and potentially treated. The etiology of fatigue related to sleep problems in people with MS is multifactorial and not just due to obstructive sleep apnea,” said lead author Jared Srinivasan, clinical research coordinator at South Shore Neurologic Associates in East Northport, New York, and colleagues.

Fatigue is common in patients with MS and can be disabling. For many patients with MS, sleep apnea is the underlying cause of fatigue. PLMS – leg movements that usually occur at 20- to 40-second intervals during sleep – are not commonly reported in MS. These movements cause sleep fragmentation, increase the energy cost of sleep, and contribute to daytime somnolence. Patients with PLMS often are unaware that they have them and do not report related symptoms unless they are specifically questioned about them. Polysomnography (PSG) is an effective, objective method of evaluating a patient for PLMS, but previous studies of PLMS in patients with MS have been small.

Mr. Srinivasan and colleagues performed a retrospective analysis to investigate the incidence and degree of PLMS in people with MS who had reported fatigue, had not previously been diagnosed as having sleep apnea or PLMS, and agreed to undergo overnight PSG.

The investigators included 292 participants in their study. The population’s average age was 47.3 years. Approximately 81% of patients were female. About 41% of the population had a PLMS index (PLMS per hour) greater than 0. Of participants with PSG-identified PLMS, 10% had a PLMS index of 5-10, 5% had a PLMS index of 11-21, and 12% had a PLMS index greater than 21. About 38% of the population experienced arousal because of PLMS. Of patients with arousal, 34% had a PLMS arousal index (number of arousals per hour) between 0 and 5, 31% had PLMS arousal index of 5-20, 14% had a PLMS arousal index of 20-50, and 21% had a PLMS arousal index greater than 50.

The investigators did not receive financial support for this study and did not report disclosures.
 

[email protected]

SOURCE: Srinivasan J et al. CMSC 2019. Abstract QOL29.

Seattle – Periodic limb movements during sleep (PLMS) are common in patients with multiple sclerosis (MS) who report fatigue, according to a retrospective analysis described at the annual meeting of the Consortium of Multiple Sclerosis Centers.

“PLMS may contribute to daytime sleepiness and should be recognized and potentially treated. The etiology of fatigue related to sleep problems in people with MS is multifactorial and not just due to obstructive sleep apnea,” said lead author Jared Srinivasan, clinical research coordinator at South Shore Neurologic Associates in East Northport, New York, and colleagues.

Fatigue is common in patients with MS and can be disabling. For many patients with MS, sleep apnea is the underlying cause of fatigue. PLMS – leg movements that usually occur at 20- to 40-second intervals during sleep – are not commonly reported in MS. These movements cause sleep fragmentation, increase the energy cost of sleep, and contribute to daytime somnolence. Patients with PLMS often are unaware that they have them and do not report related symptoms unless they are specifically questioned about them. Polysomnography (PSG) is an effective, objective method of evaluating a patient for PLMS, but previous studies of PLMS in patients with MS have been small.

Mr. Srinivasan and colleagues performed a retrospective analysis to investigate the incidence and degree of PLMS in people with MS who had reported fatigue, had not previously been diagnosed as having sleep apnea or PLMS, and agreed to undergo overnight PSG.

The investigators included 292 participants in their study. The population’s average age was 47.3 years. Approximately 81% of patients were female. About 41% of the population had a PLMS index (PLMS per hour) greater than 0. Of participants with PSG-identified PLMS, 10% had a PLMS index of 5-10, 5% had a PLMS index of 11-21, and 12% had a PLMS index greater than 21. About 38% of the population experienced arousal because of PLMS. Of patients with arousal, 34% had a PLMS arousal index (number of arousals per hour) between 0 and 5, 31% had PLMS arousal index of 5-20, 14% had a PLMS arousal index of 20-50, and 21% had a PLMS arousal index greater than 50.

The investigators did not receive financial support for this study and did not report disclosures.
 

[email protected]

SOURCE: Srinivasan J et al. CMSC 2019. Abstract QOL29.

SEATTLE – Future behavioral interventions for improving sleep in patients with multiple sclerosis (MS) should focus on sedentary behavior and light physical activity, according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Reducing sedentary behavior among young adults with MS could improve sleep efficiency, and increasing the time spent in light physical activity could improve sleep latency for older adults with MS, said the researchers.

Sleep quality generally decreases with age. Among patients with MS, the prevalence of sleep problems increases threefold with age. Although data indicate that physical activity has many benefits for patients with MS, little research has examined the relationships between physical activity, sedentary behavior, and sleep quality across the lifespan in this population.

Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham, and colleagues recruited 127 adults with MS representing three age groups into a study. In all, 42 participants were younger (aged 20-39 years), 44 were middle-aged (40-59 years), and 41 were older (60-79 years). Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Patient-Determined Disease Steps (PDDS) scale. Each participant also wore an accelerometer for 7 days. Ms. Cederberg and colleagues analyzed the accelerometer data to determine the time per day that participants spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior using MS-specific cutpoints.

Compared with younger adults, older adults had significantly lower PSQI global scores and reported more frequent use of sleeping medications. Compared with middle-aged adults, older adults had significantly higher disability levels and spent significantly less time in moderate-to-vigorous physical activity. In addition, among older adults, sleep latency was negatively associated with time spent in light physical activity, and clinical disability was inversely associated with time spent in moderate-to-vigorous physical activity.

In younger adults, habitual sleep efficiency was inversely associated with time spent in sedentary behavior. The researchers found no significant associations between these variables in middle-aged adults.
 

[email protected]

SOURCE: Cederberg KLJ et al. CMSC 2019. Abstract DXA05.

SEATTLE – Future behavioral interventions for improving sleep in patients with multiple sclerosis (MS) should focus on sedentary behavior and light physical activity, according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Reducing sedentary behavior among young adults with MS could improve sleep efficiency, and increasing the time spent in light physical activity could improve sleep latency for older adults with MS, said the researchers.

Sleep quality generally decreases with age. Among patients with MS, the prevalence of sleep problems increases threefold with age. Although data indicate that physical activity has many benefits for patients with MS, little research has examined the relationships between physical activity, sedentary behavior, and sleep quality across the lifespan in this population.

Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham, and colleagues recruited 127 adults with MS representing three age groups into a study. In all, 42 participants were younger (aged 20-39 years), 44 were middle-aged (40-59 years), and 41 were older (60-79 years). Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Patient-Determined Disease Steps (PDDS) scale. Each participant also wore an accelerometer for 7 days. Ms. Cederberg and colleagues analyzed the accelerometer data to determine the time per day that participants spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior using MS-specific cutpoints.

Compared with younger adults, older adults had significantly lower PSQI global scores and reported more frequent use of sleeping medications. Compared with middle-aged adults, older adults had significantly higher disability levels and spent significantly less time in moderate-to-vigorous physical activity. In addition, among older adults, sleep latency was negatively associated with time spent in light physical activity, and clinical disability was inversely associated with time spent in moderate-to-vigorous physical activity.

In younger adults, habitual sleep efficiency was inversely associated with time spent in sedentary behavior. The researchers found no significant associations between these variables in middle-aged adults.
 

[email protected]

SOURCE: Cederberg KLJ et al. CMSC 2019. Abstract DXA05.

SEATTLE – Future behavioral interventions for improving sleep in patients with multiple sclerosis (MS) should focus on sedentary behavior and light physical activity, according to a study presented at the annual meeting of the Consortium of Multiple Sclerosis Centers. Reducing sedentary behavior among young adults with MS could improve sleep efficiency, and increasing the time spent in light physical activity could improve sleep latency for older adults with MS, said the researchers.

Sleep quality generally decreases with age. Among patients with MS, the prevalence of sleep problems increases threefold with age. Although data indicate that physical activity has many benefits for patients with MS, little research has examined the relationships between physical activity, sedentary behavior, and sleep quality across the lifespan in this population.

Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham, and colleagues recruited 127 adults with MS representing three age groups into a study. In all, 42 participants were younger (aged 20-39 years), 44 were middle-aged (40-59 years), and 41 were older (60-79 years). Participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Patient-Determined Disease Steps (PDDS) scale. Each participant also wore an accelerometer for 7 days. Ms. Cederberg and colleagues analyzed the accelerometer data to determine the time per day that participants spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior using MS-specific cutpoints.

Compared with younger adults, older adults had significantly lower PSQI global scores and reported more frequent use of sleeping medications. Compared with middle-aged adults, older adults had significantly higher disability levels and spent significantly less time in moderate-to-vigorous physical activity. In addition, among older adults, sleep latency was negatively associated with time spent in light physical activity, and clinical disability was inversely associated with time spent in moderate-to-vigorous physical activity.

In younger adults, habitual sleep efficiency was inversely associated with time spent in sedentary behavior. The researchers found no significant associations between these variables in middle-aged adults.
 

[email protected]

SOURCE: Cederberg KLJ et al. CMSC 2019. Abstract DXA05.

SEATTLE – Anxiety and fatigue interact significantly and affect the rate of processing speed in patients with multiple sclerosis (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.

[email protected]

SEATTLE – Anxiety and fatigue interact significantly and affect the rate of processing speed in patients with multiple sclerosis (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.

[email protected]

SEATTLE – Anxiety and fatigue interact significantly and affect the rate of processing speed in patients with multiple sclerosis (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.

[email protected]

SEATTLE – More than one quarter of people with multiple sclerosis (MS) may be underemployed or unemployed, 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.

[email protected]

SEATTLE – More than one quarter of people with multiple sclerosis (MS) may be underemployed or unemployed, 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.

[email protected]

SEATTLE – More than one quarter of people with multiple sclerosis (MS) may be underemployed or unemployed, 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.

[email protected]

Seattle – Among patients with multiple sclerosis (MS) who receive treatment with alemtuzumab, those with an Expanded Disability Status Scale (EDSS) score between 4.0 and 4.5 are most likely to achieve confirmed disability improvement, 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.

[email protected]

SOURCE: Hunter SF et al. CMSC 2019. Abstract DXT08.

Seattle – Among patients with multiple sclerosis (MS) who receive treatment with alemtuzumab, those with an Expanded Disability Status Scale (EDSS) score between 4.0 and 4.5 are most likely to achieve confirmed disability improvement, 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.

[email protected]

SOURCE: Hunter SF et al. CMSC 2019. Abstract DXT08.

Seattle – Among patients with multiple sclerosis (MS) who receive treatment with alemtuzumab, those with an Expanded Disability Status Scale (EDSS) score between 4.0 and 4.5 are most likely to achieve confirmed disability improvement, 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.

[email protected]

SOURCE: Hunter SF et al. CMSC 2019. Abstract DXT08.

PHILADELPHIA – Inebilizumab, a humanized IgG monoclonal antibody with high affinity for CD19, reduces the risk of neuromyelitis optica spectrum disorder (NMOSD) attacks, according to results presented at the annual meeting of the American Academy of Neurology. The antibody also reduces the risks of disability worsening, MRI lesion activity, and hospitalization.

No approved therapies are available for NMOSD, which is thought to be a B-cell-mediated disorder. Research suggests that CD19 is a potential therapeutic target in NMOSD. Inebilizumab has a high affinity for CD19 and reliably depleted B cells in preclinical and clinical studies.
 

Participants did not receive concomitant immunosuppressants

Bruce Cree, MD, PhD, clinical research director at the University of California, San Francisco, Multiple Sclerosis Center, and colleagues conducted a phase 3 study to evaluate the safety and efficacy of inebilizumab in NMOSD. Eligible participants were older than 18 years, had NMOSD, and were seropositive for aquaporin-4 (AQP4) antibodies. Seronegative patients were allowed to participate, provided that they met the 2006 Wingerchuk criteria for neuromyelitis optica. Participants were required to have had one attack in the previous year or two attacks in the 2 previous years. Participants had a wide range of disability. No background use of immune suppressants was permitted.

The trial was conducted at 99 centers in 24 countries. After a 4-week screening period, investigators randomized patients in a 3:1 ratio to inebilizumab or placebo. Treatment was administered on days 1 and 15 by IV infusion. The randomized, controlled period lasted for 197 days. If a participant did not have a relapse by the end of this period, he or she was given the choice of participating in a yearlong open-label study, in which he or she would receive 300 mg of inebilizumab every 6 months. Participants who had an attack were treated for the attack.

An independent eligibility committee reviewed and confirmed the diagnostic criteria for AQP4 seronegative participants. A masked attack-adjudication committee provided real-time assessment of NMOSD attacks. An independent data monitoring committee reviewed patient safety and ensured the ethical conduct of the study.

The trial’s primary endpoint was the time from randomization to first attack. Secondary endpoints included a measure of disability, a measure of visual acuity, cumulative lesions on MRI, and NMOSD-related inpatient hospitalizations.
 

Treatment reduced the risk of hospitalization

Dr. Cree and colleagues screened 467 subjects and randomized 231. Among those patients, 175 received inebilizumab, and 56 received placebo. The population’s mean age was 43 years. About 90% were women, and 72% were white or Asian. The median baseline disability score was 3.5, indicating moderate disability. More than 90% of patients were AQP4 seropositive. The mean number of attacks at entry was 4.3. About 60% of participants had had prior exposure to immune suppressants.

Enrollment into the randomized, controlled period was stopped at 231 patients after 43 attacks had occurred, based on the recommendation of the independent data monitoring committee, which concluded that further recruitment into the placebo arm would not be ethical. The committee also recommended that all participants be shifted into the open-label period.

Among AQP4 seropositive patients, 88% of the inebilizumab group did not have an attack, compared with 57% of the control group. This result represents a 77% reduction in the risk of a relapse following inebilizumab treatment. The number needed to treat was 3.23. In the population overall, 87% of patients treated with inebilizumab did not have an attack, compared with 60% of controls, which corresponded to a 73% reduction in risk of an attack and a number needed to treat of 3.7.

In addition, Dr. Cree and colleagues found that inebilizumab was associated with a 63% reduction in risk of disability, a 43% reduction in risk of developing new lesions, and a 71% reduction in NMOSD-related hospitalizations. These results were statistically significant and clinically meaningful, he said. The only secondary endpoint that was not met was the difference in binocular low-contrast visual acuity scores. “This [result] may be due to the low frequency of optic neuritis events, a floor effect within the placebo arm (many of those patients had profound visual loss at baseline), or selection of a binocular acuity test that diluted the impact of monocular events,” said Dr. Cree.

Adverse events and serious adverse events were well balanced between the two treatment arms. The rate of infusion-related reactions was low in both arms and was “perhaps slightly lower in the inebilizumab treatment arm,” said Dr. Cree. No deaths occurred during the randomized, controlled period, and the researchers found no pattern of serious adverse events. Two deaths occurred in the open-label period: one related to a severe attack, and the other related to a brain event of unclear etiology without definite diagnosis.

B cells were depleted within approximately 4 weeks of treatment, and this depletion was sustained throughout the randomized, controlled period.

This study was funded by Viela Bio and MedImmune. Dr. Cree has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.

[email protected]

SOURCE: Cree B et al. AAN 2019. Abstract Plen02.001.

PHILADELPHIA – Inebilizumab, a humanized IgG monoclonal antibody with high affinity for CD19, reduces the risk of neuromyelitis optica spectrum disorder (NMOSD) attacks, according to results presented at the annual meeting of the American Academy of Neurology. The antibody also reduces the risks of disability worsening, MRI lesion activity, and hospitalization.

No approved therapies are available for NMOSD, which is thought to be a B-cell-mediated disorder. Research suggests that CD19 is a potential therapeutic target in NMOSD. Inebilizumab has a high affinity for CD19 and reliably depleted B cells in preclinical and clinical studies.
 

Participants did not receive concomitant immunosuppressants

Bruce Cree, MD, PhD, clinical research director at the University of California, San Francisco, Multiple Sclerosis Center, and colleagues conducted a phase 3 study to evaluate the safety and efficacy of inebilizumab in NMOSD. Eligible participants were older than 18 years, had NMOSD, and were seropositive for aquaporin-4 (AQP4) antibodies. Seronegative patients were allowed to participate, provided that they met the 2006 Wingerchuk criteria for neuromyelitis optica. Participants were required to have had one attack in the previous year or two attacks in the 2 previous years. Participants had a wide range of disability. No background use of immune suppressants was permitted.

The trial was conducted at 99 centers in 24 countries. After a 4-week screening period, investigators randomized patients in a 3:1 ratio to inebilizumab or placebo. Treatment was administered on days 1 and 15 by IV infusion. The randomized, controlled period lasted for 197 days. If a participant did not have a relapse by the end of this period, he or she was given the choice of participating in a yearlong open-label study, in which he or she would receive 300 mg of inebilizumab every 6 months. Participants who had an attack were treated for the attack.

An independent eligibility committee reviewed and confirmed the diagnostic criteria for AQP4 seronegative participants. A masked attack-adjudication committee provided real-time assessment of NMOSD attacks. An independent data monitoring committee reviewed patient safety and ensured the ethical conduct of the study.

The trial’s primary endpoint was the time from randomization to first attack. Secondary endpoints included a measure of disability, a measure of visual acuity, cumulative lesions on MRI, and NMOSD-related inpatient hospitalizations.
 

Treatment reduced the risk of hospitalization

Dr. Cree and colleagues screened 467 subjects and randomized 231. Among those patients, 175 received inebilizumab, and 56 received placebo. The population’s mean age was 43 years. About 90% were women, and 72% were white or Asian. The median baseline disability score was 3.5, indicating moderate disability. More than 90% of patients were AQP4 seropositive. The mean number of attacks at entry was 4.3. About 60% of participants had had prior exposure to immune suppressants.

Enrollment into the randomized, controlled period was stopped at 231 patients after 43 attacks had occurred, based on the recommendation of the independent data monitoring committee, which concluded that further recruitment into the placebo arm would not be ethical. The committee also recommended that all participants be shifted into the open-label period.

Among AQP4 seropositive patients, 88% of the inebilizumab group did not have an attack, compared with 57% of the control group. This result represents a 77% reduction in the risk of a relapse following inebilizumab treatment. The number needed to treat was 3.23. In the population overall, 87% of patients treated with inebilizumab did not have an attack, compared with 60% of controls, which corresponded to a 73% reduction in risk of an attack and a number needed to treat of 3.7.

In addition, Dr. Cree and colleagues found that inebilizumab was associated with a 63% reduction in risk of disability, a 43% reduction in risk of developing new lesions, and a 71% reduction in NMOSD-related hospitalizations. These results were statistically significant and clinically meaningful, he said. The only secondary endpoint that was not met was the difference in binocular low-contrast visual acuity scores. “This [result] may be due to the low frequency of optic neuritis events, a floor effect within the placebo arm (many of those patients had profound visual loss at baseline), or selection of a binocular acuity test that diluted the impact of monocular events,” said Dr. Cree.

Adverse events and serious adverse events were well balanced between the two treatment arms. The rate of infusion-related reactions was low in both arms and was “perhaps slightly lower in the inebilizumab treatment arm,” said Dr. Cree. No deaths occurred during the randomized, controlled period, and the researchers found no pattern of serious adverse events. Two deaths occurred in the open-label period: one related to a severe attack, and the other related to a brain event of unclear etiology without definite diagnosis.

B cells were depleted within approximately 4 weeks of treatment, and this depletion was sustained throughout the randomized, controlled period.

This study was funded by Viela Bio and MedImmune. Dr. Cree has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.

[email protected]

SOURCE: Cree B et al. AAN 2019. Abstract Plen02.001.

PHILADELPHIA – Inebilizumab, a humanized IgG monoclonal antibody with high affinity for CD19, reduces the risk of neuromyelitis optica spectrum disorder (NMOSD) attacks, according to results presented at the annual meeting of the American Academy of Neurology. The antibody also reduces the risks of disability worsening, MRI lesion activity, and hospitalization.

No approved therapies are available for NMOSD, which is thought to be a B-cell-mediated disorder. Research suggests that CD19 is a potential therapeutic target in NMOSD. Inebilizumab has a high affinity for CD19 and reliably depleted B cells in preclinical and clinical studies.
 

Participants did not receive concomitant immunosuppressants

Bruce Cree, MD, PhD, clinical research director at the University of California, San Francisco, Multiple Sclerosis Center, and colleagues conducted a phase 3 study to evaluate the safety and efficacy of inebilizumab in NMOSD. Eligible participants were older than 18 years, had NMOSD, and were seropositive for aquaporin-4 (AQP4) antibodies. Seronegative patients were allowed to participate, provided that they met the 2006 Wingerchuk criteria for neuromyelitis optica. Participants were required to have had one attack in the previous year or two attacks in the 2 previous years. Participants had a wide range of disability. No background use of immune suppressants was permitted.

The trial was conducted at 99 centers in 24 countries. After a 4-week screening period, investigators randomized patients in a 3:1 ratio to inebilizumab or placebo. Treatment was administered on days 1 and 15 by IV infusion. The randomized, controlled period lasted for 197 days. If a participant did not have a relapse by the end of this period, he or she was given the choice of participating in a yearlong open-label study, in which he or she would receive 300 mg of inebilizumab every 6 months. Participants who had an attack were treated for the attack.

An independent eligibility committee reviewed and confirmed the diagnostic criteria for AQP4 seronegative participants. A masked attack-adjudication committee provided real-time assessment of NMOSD attacks. An independent data monitoring committee reviewed patient safety and ensured the ethical conduct of the study.

The trial’s primary endpoint was the time from randomization to first attack. Secondary endpoints included a measure of disability, a measure of visual acuity, cumulative lesions on MRI, and NMOSD-related inpatient hospitalizations.
 

Treatment reduced the risk of hospitalization

Dr. Cree and colleagues screened 467 subjects and randomized 231. Among those patients, 175 received inebilizumab, and 56 received placebo. The population’s mean age was 43 years. About 90% were women, and 72% were white or Asian. The median baseline disability score was 3.5, indicating moderate disability. More than 90% of patients were AQP4 seropositive. The mean number of attacks at entry was 4.3. About 60% of participants had had prior exposure to immune suppressants.

Enrollment into the randomized, controlled period was stopped at 231 patients after 43 attacks had occurred, based on the recommendation of the independent data monitoring committee, which concluded that further recruitment into the placebo arm would not be ethical. The committee also recommended that all participants be shifted into the open-label period.

Among AQP4 seropositive patients, 88% of the inebilizumab group did not have an attack, compared with 57% of the control group. This result represents a 77% reduction in the risk of a relapse following inebilizumab treatment. The number needed to treat was 3.23. In the population overall, 87% of patients treated with inebilizumab did not have an attack, compared with 60% of controls, which corresponded to a 73% reduction in risk of an attack and a number needed to treat of 3.7.

In addition, Dr. Cree and colleagues found that inebilizumab was associated with a 63% reduction in risk of disability, a 43% reduction in risk of developing new lesions, and a 71% reduction in NMOSD-related hospitalizations. These results were statistically significant and clinically meaningful, he said. The only secondary endpoint that was not met was the difference in binocular low-contrast visual acuity scores. “This [result] may be due to the low frequency of optic neuritis events, a floor effect within the placebo arm (many of those patients had profound visual loss at baseline), or selection of a binocular acuity test that diluted the impact of monocular events,” said Dr. Cree.

Adverse events and serious adverse events were well balanced between the two treatment arms. The rate of infusion-related reactions was low in both arms and was “perhaps slightly lower in the inebilizumab treatment arm,” said Dr. Cree. No deaths occurred during the randomized, controlled period, and the researchers found no pattern of serious adverse events. Two deaths occurred in the open-label period: one related to a severe attack, and the other related to a brain event of unclear etiology without definite diagnosis.

B cells were depleted within approximately 4 weeks of treatment, and this depletion was sustained throughout the randomized, controlled period.

This study was funded by Viela Bio and MedImmune. Dr. Cree has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Abbvie, Akili, Biogen, EMD Serono, GeNeuro and Novartis.

[email protected]

SOURCE: Cree B et al. AAN 2019. Abstract Plen02.001.

PHILADELPHIA – About 17% of patients discharged from a hospital after treatment for generalized convulsive status epilepticus are readmitted within 30 days, according to research presented at the annual meeting of the American Academy of Neurology. It is possible to identify patients at high risk of readmission, which could allow neurologists to reduce their clinical and economic burden, said the investigators.

Status epilepticus is a major neurologic emergency. Patients often have significant disability and may represent a burden on their families and on the health care system. To identify independent predictors of 30-day hospital readmission among patients discharged after generalized convulsive status epilepticus, Mohamad Rahwan, MD, a neurologist at the Medical University of South Carolina, Charleston, and colleagues examined data from the 2014 Nationwide Readmission Database.

The investigators included adults with a primary discharge diagnosis of generalized convulsive status epilepticus, identified by the ICD-9-CM code 345.3, in their study. Patients who died during hospitalization, had missing information on the length of stay, or were discharged in December 2014 were excluded from analysis. Dr. Rahwan and colleagues calculated the overall 30-day readmission rate for the sample and compared prespecified groups by their 30-day readmission status. They performed multiple logistic regression analysis to identify independent predictors of 30-day readmission, adjusting for potential confounders.

In all, 14,562 adults were discharged with a diagnosis of generalized convulsive status epilepticus. Of this population, 2,520 patients (17.3%) were readmitted within 30 days. Multivariate logistic regression analysis indicated that patients discharged against medical advice (odds ratio, 1.45), those discharged to short-term hospital (OR, 1.39), those with comorbid conditions (OR for Charlson Comorbidity Index of 1, 1.12; OR for Charlson Comorbidity Index of 2 or greater, 1.32), and those with a length of stay exceeding 6 days (OR, 1.42) had a greater risk of 30-day readmission. The researchers observed an inverse association for patients aged 45 years or older and for those in high-income households. “Greater attention to high-risk subgroups may identify opportunities to ameliorate the clinical and economic burden of early readmissions after generalized convulsive status epilepticus,” said the researchers.

The researchers had no disclosures.

[email protected]

SOURCE: Rahwan M et al. AAN 2019, Abstract S36.006.

PHILADELPHIA – About 17% of patients discharged from a hospital after treatment for generalized convulsive status epilepticus are readmitted within 30 days, according to research presented at the annual meeting of the American Academy of Neurology. It is possible to identify patients at high risk of readmission, which could allow neurologists to reduce their clinical and economic burden, said the investigators.

Status epilepticus is a major neurologic emergency. Patients often have significant disability and may represent a burden on their families and on the health care system. To identify independent predictors of 30-day hospital readmission among patients discharged after generalized convulsive status epilepticus, Mohamad Rahwan, MD, a neurologist at the Medical University of South Carolina, Charleston, and colleagues examined data from the 2014 Nationwide Readmission Database.

The investigators included adults with a primary discharge diagnosis of generalized convulsive status epilepticus, identified by the ICD-9-CM code 345.3, in their study. Patients who died during hospitalization, had missing information on the length of stay, or were discharged in December 2014 were excluded from analysis. Dr. Rahwan and colleagues calculated the overall 30-day readmission rate for the sample and compared prespecified groups by their 30-day readmission status. They performed multiple logistic regression analysis to identify independent predictors of 30-day readmission, adjusting for potential confounders.

In all, 14,562 adults were discharged with a diagnosis of generalized convulsive status epilepticus. Of this population, 2,520 patients (17.3%) were readmitted within 30 days. Multivariate logistic regression analysis indicated that patients discharged against medical advice (odds ratio, 1.45), those discharged to short-term hospital (OR, 1.39), those with comorbid conditions (OR for Charlson Comorbidity Index of 1, 1.12; OR for Charlson Comorbidity Index of 2 or greater, 1.32), and those with a length of stay exceeding 6 days (OR, 1.42) had a greater risk of 30-day readmission. The researchers observed an inverse association for patients aged 45 years or older and for those in high-income households. “Greater attention to high-risk subgroups may identify opportunities to ameliorate the clinical and economic burden of early readmissions after generalized convulsive status epilepticus,” said the researchers.

The researchers had no disclosures.

[email protected]

SOURCE: Rahwan M et al. AAN 2019, Abstract S36.006.

PHILADELPHIA – About 17% of patients discharged from a hospital after treatment for generalized convulsive status epilepticus are readmitted within 30 days, according to research presented at the annual meeting of the American Academy of Neurology. It is possible to identify patients at high risk of readmission, which could allow neurologists to reduce their clinical and economic burden, said the investigators.

Status epilepticus is a major neurologic emergency. Patients often have significant disability and may represent a burden on their families and on the health care system. To identify independent predictors of 30-day hospital readmission among patients discharged after generalized convulsive status epilepticus, Mohamad Rahwan, MD, a neurologist at the Medical University of South Carolina, Charleston, and colleagues examined data from the 2014 Nationwide Readmission Database.

The investigators included adults with a primary discharge diagnosis of generalized convulsive status epilepticus, identified by the ICD-9-CM code 345.3, in their study. Patients who died during hospitalization, had missing information on the length of stay, or were discharged in December 2014 were excluded from analysis. Dr. Rahwan and colleagues calculated the overall 30-day readmission rate for the sample and compared prespecified groups by their 30-day readmission status. They performed multiple logistic regression analysis to identify independent predictors of 30-day readmission, adjusting for potential confounders.

In all, 14,562 adults were discharged with a diagnosis of generalized convulsive status epilepticus. Of this population, 2,520 patients (17.3%) were readmitted within 30 days. Multivariate logistic regression analysis indicated that patients discharged against medical advice (odds ratio, 1.45), those discharged to short-term hospital (OR, 1.39), those with comorbid conditions (OR for Charlson Comorbidity Index of 1, 1.12; OR for Charlson Comorbidity Index of 2 or greater, 1.32), and those with a length of stay exceeding 6 days (OR, 1.42) had a greater risk of 30-day readmission. The researchers observed an inverse association for patients aged 45 years or older and for those in high-income households. “Greater attention to high-risk subgroups may identify opportunities to ameliorate the clinical and economic burden of early readmissions after generalized convulsive status epilepticus,” said the researchers.

The researchers had no disclosures.

[email protected]

SOURCE: Rahwan M et al. AAN 2019, Abstract S36.006.

PHILADELPHIA – Structural and functional network MRI measures may predict long-term clinical worsening in patients with relapsing remitting multiple sclerosis (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..
 

[email protected]

SOURCE: Filippi M et al. AAN 2019, Abstract S49.004.

PHILADELPHIA – Structural and functional network MRI measures may predict long-term clinical worsening in patients with relapsing remitting multiple sclerosis (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..
 

[email protected]

SOURCE: Filippi M et al. AAN 2019, Abstract S49.004.

PHILADELPHIA – Structural and functional network MRI measures may predict long-term clinical worsening in patients with relapsing remitting multiple sclerosis (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..
 

[email protected]

SOURCE: Filippi M et al. AAN 2019, Abstract S49.004.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

[email protected]

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

[email protected]

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

[email protected]

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

Philadelphia – Adjunctive cannabidiol (CBD) reduces seizure frequency in patients with Dravet syndrome, according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.

“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”

Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.

The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.

Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.


The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.

The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.

“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.

GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.

[email protected]

SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.

Philadelphia – Adjunctive cannabidiol (CBD) reduces seizure frequency in patients with Dravet syndrome, according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.

“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”

Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.

The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.

Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.


The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.

The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.

“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.

GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.

[email protected]

SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.

Philadelphia – Adjunctive cannabidiol (CBD) reduces seizure frequency in patients with Dravet syndrome, according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.

“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said Ian Miller, MD, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a press release. “The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with CBD is a major victory.”

Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.

The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.

Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.


The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.

The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.

“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.

GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.

[email protected]

SOURCE: Miller I et al. AAN 2019, Abstract P3.6-0.76.