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Do Cardiovascular Risk Factors Contribute to Brain Atrophy in MS?
LOS ANGELES—Hypertension and heart disease may contribute to advanced central and white matter atrophy in patients with multiple sclerosis (MS) over five years, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology.
The findings suggest that management of cardiovascular comorbidities in MS may improve overall long-term disease outcomes, said Dejan Jakimovski, MD, a clinical research fellow at the Buffalo Neuroimaging Analysis Center at the University at Buffalo, New York, and colleagues.
Cardiovascular diseases and risk factors are more common in patients with MS, compared with healthy individuals, and cross-sectional studies have linked smoking, hypertension, hyperlipidemia, and heart disease to lesion burden and brain atrophy, the researchers said.
To determine the influence of cardiovascular diseases over five years in a larger number of patients with MS, Dr. Jakimovski and colleagues examined data from 194 patients with MS in a prospective study of cardiovascular, environmental, and genetic risk factors in MS (CEG-MS). Patients in the study underwent clinical evaluation and completed questionnaires about cardiovascular risk factors (ie, hypertension, hyperlipidemia, heart disease, smoking, diabetes, and obesity or overweight status). The researchers assessed T2 and T1 lesion volumes and volumes of whole brain, gray matter, white matter, cortex, and lateral ventricles using 3-T MRI. They used analysis of covariance adjusted for age, sex, and disease duration to detect significant differences between patients with and without cardiovascular risk factors.
The 194 patients with MS (73.7% female; mean age, 46.7) had an average disease duration of 13.6 years, a median baseline Expanded Disability Status Scale (EDSS) score of 2.5, and a median EDSS at follow-up of 3. Mean BMI was 27.6, 14.9% had hypertension, and 9.8% had heart disease.
At baseline, patients with hypertension had larger lateral ventricular volume, compared with patients without hypertension (66.1 mL vs 49.9 mL). Over the follow-up period, the percentage lateral ventricular volume change was significantly greater in patients with hypertension, compared with patients without hypertension (24.5% vs 14.1%). Over the follow-up period, patients with a diagnosis of heart disease had greater white matter volume loss, compared with those without heart disease (–4.2% vs –0.7%).
Hyperlipidemia, diabetes, smoking, and obesity or overweight status
—Jake Remaly
LOS ANGELES—Hypertension and heart disease may contribute to advanced central and white matter atrophy in patients with multiple sclerosis (MS) over five years, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology.
The findings suggest that management of cardiovascular comorbidities in MS may improve overall long-term disease outcomes, said Dejan Jakimovski, MD, a clinical research fellow at the Buffalo Neuroimaging Analysis Center at the University at Buffalo, New York, and colleagues.
Cardiovascular diseases and risk factors are more common in patients with MS, compared with healthy individuals, and cross-sectional studies have linked smoking, hypertension, hyperlipidemia, and heart disease to lesion burden and brain atrophy, the researchers said.
To determine the influence of cardiovascular diseases over five years in a larger number of patients with MS, Dr. Jakimovski and colleagues examined data from 194 patients with MS in a prospective study of cardiovascular, environmental, and genetic risk factors in MS (CEG-MS). Patients in the study underwent clinical evaluation and completed questionnaires about cardiovascular risk factors (ie, hypertension, hyperlipidemia, heart disease, smoking, diabetes, and obesity or overweight status). The researchers assessed T2 and T1 lesion volumes and volumes of whole brain, gray matter, white matter, cortex, and lateral ventricles using 3-T MRI. They used analysis of covariance adjusted for age, sex, and disease duration to detect significant differences between patients with and without cardiovascular risk factors.
The 194 patients with MS (73.7% female; mean age, 46.7) had an average disease duration of 13.6 years, a median baseline Expanded Disability Status Scale (EDSS) score of 2.5, and a median EDSS at follow-up of 3. Mean BMI was 27.6, 14.9% had hypertension, and 9.8% had heart disease.
At baseline, patients with hypertension had larger lateral ventricular volume, compared with patients without hypertension (66.1 mL vs 49.9 mL). Over the follow-up period, the percentage lateral ventricular volume change was significantly greater in patients with hypertension, compared with patients without hypertension (24.5% vs 14.1%). Over the follow-up period, patients with a diagnosis of heart disease had greater white matter volume loss, compared with those without heart disease (–4.2% vs –0.7%).
Hyperlipidemia, diabetes, smoking, and obesity or overweight status
—Jake Remaly
LOS ANGELES—Hypertension and heart disease may contribute to advanced central and white matter atrophy in patients with multiple sclerosis (MS) over five years, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology.
The findings suggest that management of cardiovascular comorbidities in MS may improve overall long-term disease outcomes, said Dejan Jakimovski, MD, a clinical research fellow at the Buffalo Neuroimaging Analysis Center at the University at Buffalo, New York, and colleagues.
Cardiovascular diseases and risk factors are more common in patients with MS, compared with healthy individuals, and cross-sectional studies have linked smoking, hypertension, hyperlipidemia, and heart disease to lesion burden and brain atrophy, the researchers said.
To determine the influence of cardiovascular diseases over five years in a larger number of patients with MS, Dr. Jakimovski and colleagues examined data from 194 patients with MS in a prospective study of cardiovascular, environmental, and genetic risk factors in MS (CEG-MS). Patients in the study underwent clinical evaluation and completed questionnaires about cardiovascular risk factors (ie, hypertension, hyperlipidemia, heart disease, smoking, diabetes, and obesity or overweight status). The researchers assessed T2 and T1 lesion volumes and volumes of whole brain, gray matter, white matter, cortex, and lateral ventricles using 3-T MRI. They used analysis of covariance adjusted for age, sex, and disease duration to detect significant differences between patients with and without cardiovascular risk factors.
The 194 patients with MS (73.7% female; mean age, 46.7) had an average disease duration of 13.6 years, a median baseline Expanded Disability Status Scale (EDSS) score of 2.5, and a median EDSS at follow-up of 3. Mean BMI was 27.6, 14.9% had hypertension, and 9.8% had heart disease.
At baseline, patients with hypertension had larger lateral ventricular volume, compared with patients without hypertension (66.1 mL vs 49.9 mL). Over the follow-up period, the percentage lateral ventricular volume change was significantly greater in patients with hypertension, compared with patients without hypertension (24.5% vs 14.1%). Over the follow-up period, patients with a diagnosis of heart disease had greater white matter volume loss, compared with those without heart disease (–4.2% vs –0.7%).
Hyperlipidemia, diabetes, smoking, and obesity or overweight status
—Jake Remaly
Interim Results Show Efficacy for a Novel MS Drug
LOS ANGELES—Preliminary results for annualized relapse rate and MRI parameters support ALKS 8700 (also known as BIIB098) as an oral treatment for patients with relapsing-remitting multiple sclerosis (MS), said Richard A. Leigh-Pemberton, MD, and colleagues, who presented interim phase III findings at the 70th Annual Meeting of the American Academy of Neurology. Dr. Leigh-Pemberton is Senior Medical Director at Alkermes in Waltham, Massachusetts.
ALKS 8700 is a prodrug of monomethyl fumarate, which is the active metabolite of dimethyl fumarate. It is being developed as an oral disease-modifying therapy for relapsing forms of MS and is designed to treat the disease in a manner similar to that of dimethyl fumarate, but with the potential for improved gastrointestinal tolerability. Two phase III studies are ongoing—EVOLVE-MS-1, an open-label study evaluating the long-term safety and tolerability of ALKS 8700 (462 mg twice daily) over 96 weeks, and EVOLVE-MS-2, a five-week, randomized, double-blind study evaluating the gastrointestinal tolerability of ALKS 8700 (462 mg twice daily) and dimethyl fumarate (240 mg twice daily).
Interim exploratory results on relapse rates and one-year MRI end points from the ongoing EVOLVE-MS-1 study were reported.
Approximately 900 patients will be enrolled in EVOLVE-MS-1. Main inclusion criteria include patients ages 18 to 65 with a confirmed diagnosis of relapsing-remitting MS according to the 2010 revised McDonald criteria, an Expanded Disability Status Scale (EDSS) score of 6 or lower, and no evidence of relapse within 30 days prior to starting the study drug. Main exclusion criteria include a diagnosis of progressive forms of MS, pregnancy or breastfeeding, history of other clinically significant medical condition, any clinically significant abnormal laboratory test at screening, and an absolute lymphocyte count less than 0.9 × 103/µL.
As of the January 12, 2018, data cutoff for this interim analysis, 528 de novo patients (those who had not participated in any prior study of ALKS 8700) had enrolled in EVOLVE-MS-1, and 374 had completed a one-year MRI assessment. Mean age was approximately 41, and about 70% were female. Median follow-up was 0.93 patient years for the de novo patients, and annualized relapse
This study was sponsored by Alkermes and Biogen.
—Glenn S. Williams
LOS ANGELES—Preliminary results for annualized relapse rate and MRI parameters support ALKS 8700 (also known as BIIB098) as an oral treatment for patients with relapsing-remitting multiple sclerosis (MS), said Richard A. Leigh-Pemberton, MD, and colleagues, who presented interim phase III findings at the 70th Annual Meeting of the American Academy of Neurology. Dr. Leigh-Pemberton is Senior Medical Director at Alkermes in Waltham, Massachusetts.
ALKS 8700 is a prodrug of monomethyl fumarate, which is the active metabolite of dimethyl fumarate. It is being developed as an oral disease-modifying therapy for relapsing forms of MS and is designed to treat the disease in a manner similar to that of dimethyl fumarate, but with the potential for improved gastrointestinal tolerability. Two phase III studies are ongoing—EVOLVE-MS-1, an open-label study evaluating the long-term safety and tolerability of ALKS 8700 (462 mg twice daily) over 96 weeks, and EVOLVE-MS-2, a five-week, randomized, double-blind study evaluating the gastrointestinal tolerability of ALKS 8700 (462 mg twice daily) and dimethyl fumarate (240 mg twice daily).
Interim exploratory results on relapse rates and one-year MRI end points from the ongoing EVOLVE-MS-1 study were reported.
Approximately 900 patients will be enrolled in EVOLVE-MS-1. Main inclusion criteria include patients ages 18 to 65 with a confirmed diagnosis of relapsing-remitting MS according to the 2010 revised McDonald criteria, an Expanded Disability Status Scale (EDSS) score of 6 or lower, and no evidence of relapse within 30 days prior to starting the study drug. Main exclusion criteria include a diagnosis of progressive forms of MS, pregnancy or breastfeeding, history of other clinically significant medical condition, any clinically significant abnormal laboratory test at screening, and an absolute lymphocyte count less than 0.9 × 103/µL.
As of the January 12, 2018, data cutoff for this interim analysis, 528 de novo patients (those who had not participated in any prior study of ALKS 8700) had enrolled in EVOLVE-MS-1, and 374 had completed a one-year MRI assessment. Mean age was approximately 41, and about 70% were female. Median follow-up was 0.93 patient years for the de novo patients, and annualized relapse
This study was sponsored by Alkermes and Biogen.
—Glenn S. Williams
LOS ANGELES—Preliminary results for annualized relapse rate and MRI parameters support ALKS 8700 (also known as BIIB098) as an oral treatment for patients with relapsing-remitting multiple sclerosis (MS), said Richard A. Leigh-Pemberton, MD, and colleagues, who presented interim phase III findings at the 70th Annual Meeting of the American Academy of Neurology. Dr. Leigh-Pemberton is Senior Medical Director at Alkermes in Waltham, Massachusetts.
ALKS 8700 is a prodrug of monomethyl fumarate, which is the active metabolite of dimethyl fumarate. It is being developed as an oral disease-modifying therapy for relapsing forms of MS and is designed to treat the disease in a manner similar to that of dimethyl fumarate, but with the potential for improved gastrointestinal tolerability. Two phase III studies are ongoing—EVOLVE-MS-1, an open-label study evaluating the long-term safety and tolerability of ALKS 8700 (462 mg twice daily) over 96 weeks, and EVOLVE-MS-2, a five-week, randomized, double-blind study evaluating the gastrointestinal tolerability of ALKS 8700 (462 mg twice daily) and dimethyl fumarate (240 mg twice daily).
Interim exploratory results on relapse rates and one-year MRI end points from the ongoing EVOLVE-MS-1 study were reported.
Approximately 900 patients will be enrolled in EVOLVE-MS-1. Main inclusion criteria include patients ages 18 to 65 with a confirmed diagnosis of relapsing-remitting MS according to the 2010 revised McDonald criteria, an Expanded Disability Status Scale (EDSS) score of 6 or lower, and no evidence of relapse within 30 days prior to starting the study drug. Main exclusion criteria include a diagnosis of progressive forms of MS, pregnancy or breastfeeding, history of other clinically significant medical condition, any clinically significant abnormal laboratory test at screening, and an absolute lymphocyte count less than 0.9 × 103/µL.
As of the January 12, 2018, data cutoff for this interim analysis, 528 de novo patients (those who had not participated in any prior study of ALKS 8700) had enrolled in EVOLVE-MS-1, and 374 had completed a one-year MRI assessment. Mean age was approximately 41, and about 70% were female. Median follow-up was 0.93 patient years for the de novo patients, and annualized relapse
This study was sponsored by Alkermes and Biogen.
—Glenn S. Williams
DMTs Are Associated With Reduced Stroke Risk in Patients With MS
LOS ANGELES—Among patients with multiple sclerosis (MS), treatment with disease-modifying therapy is associated with a significantly decreased likelihood of ischemic stroke, compared with no disease-modifying therapy, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology.
Stroke is a major cause of morbidity and mortality. One-third to one-half of stroke survivors have post-stoke disability. Autoimmune diseases are associated with an increased risk of ischemic stroke. To examine the role of disease-modifying therapy in the prevention of ischemic stroke in MS, Asad Ikram, MD, a clinical research fellow in the Department of Neurology at the University of New Mexico School of Medicine in Albuquerque, and colleagues conducted a nationwide, case–control, population-based study.
Investigators extracted data from the Cerner’s Health Facts database and used ICD-9/10 codes to identify all patients diagnosed with MS between 2000 and 2016. The researchers identified patients with MS who had an ischemic stroke and categorized them as having received disease-modifying therapy or not. They excluded patients younger than 18 and patients for whom they did not have information about sex.
The investigators used multiple logistic regression to evaluate the likelihood of ischemic stroke in patients treated with disease-modifying therapy. In the final model, they also adjusted for patients’ baseline characteristics and medications.
In all, Dr. Ikram and colleagues identified 57,769 patients with a diagnosis of MS, 1,349 of whom had a CT-confirmed ischemic stroke (2.34%).
The study group (ie, patients with ischemic stroke who were receiving disease-modifying therapy) included 126 patients (89 females), and the control group (ie, patients with ischemic stroke who had not received disease-modifying therapy) included 1,002 patients.
Patients not treated with disease-modifying therapy were approximately twice as likely to have an ischemic stroke, compared with patients treated with disease-modifying therapy (odds ratio = 1.91).
After controlling for covariates (eg, smoking, hypertension, diabetes, heart failure, atrial fibrillation, age, and sex), the likelihood of ischemic stroke remained higher in the untreated group.
“This study suggests that the early treatment of MS with disease-modifying therapies may reduce the risk of ischemic stroke in the MS population,” said Dr. Ikram and colleagues.
—Jake Remaly
LOS ANGELES—Among patients with multiple sclerosis (MS), treatment with disease-modifying therapy is associated with a significantly decreased likelihood of ischemic stroke, compared with no disease-modifying therapy, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology.
Stroke is a major cause of morbidity and mortality. One-third to one-half of stroke survivors have post-stoke disability. Autoimmune diseases are associated with an increased risk of ischemic stroke. To examine the role of disease-modifying therapy in the prevention of ischemic stroke in MS, Asad Ikram, MD, a clinical research fellow in the Department of Neurology at the University of New Mexico School of Medicine in Albuquerque, and colleagues conducted a nationwide, case–control, population-based study.
Investigators extracted data from the Cerner’s Health Facts database and used ICD-9/10 codes to identify all patients diagnosed with MS between 2000 and 2016. The researchers identified patients with MS who had an ischemic stroke and categorized them as having received disease-modifying therapy or not. They excluded patients younger than 18 and patients for whom they did not have information about sex.
The investigators used multiple logistic regression to evaluate the likelihood of ischemic stroke in patients treated with disease-modifying therapy. In the final model, they also adjusted for patients’ baseline characteristics and medications.
In all, Dr. Ikram and colleagues identified 57,769 patients with a diagnosis of MS, 1,349 of whom had a CT-confirmed ischemic stroke (2.34%).
The study group (ie, patients with ischemic stroke who were receiving disease-modifying therapy) included 126 patients (89 females), and the control group (ie, patients with ischemic stroke who had not received disease-modifying therapy) included 1,002 patients.
Patients not treated with disease-modifying therapy were approximately twice as likely to have an ischemic stroke, compared with patients treated with disease-modifying therapy (odds ratio = 1.91).
After controlling for covariates (eg, smoking, hypertension, diabetes, heart failure, atrial fibrillation, age, and sex), the likelihood of ischemic stroke remained higher in the untreated group.
“This study suggests that the early treatment of MS with disease-modifying therapies may reduce the risk of ischemic stroke in the MS population,” said Dr. Ikram and colleagues.
—Jake Remaly
LOS ANGELES—Among patients with multiple sclerosis (MS), treatment with disease-modifying therapy is associated with a significantly decreased likelihood of ischemic stroke, compared with no disease-modifying therapy, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology.
Stroke is a major cause of morbidity and mortality. One-third to one-half of stroke survivors have post-stoke disability. Autoimmune diseases are associated with an increased risk of ischemic stroke. To examine the role of disease-modifying therapy in the prevention of ischemic stroke in MS, Asad Ikram, MD, a clinical research fellow in the Department of Neurology at the University of New Mexico School of Medicine in Albuquerque, and colleagues conducted a nationwide, case–control, population-based study.
Investigators extracted data from the Cerner’s Health Facts database and used ICD-9/10 codes to identify all patients diagnosed with MS between 2000 and 2016. The researchers identified patients with MS who had an ischemic stroke and categorized them as having received disease-modifying therapy or not. They excluded patients younger than 18 and patients for whom they did not have information about sex.
The investigators used multiple logistic regression to evaluate the likelihood of ischemic stroke in patients treated with disease-modifying therapy. In the final model, they also adjusted for patients’ baseline characteristics and medications.
In all, Dr. Ikram and colleagues identified 57,769 patients with a diagnosis of MS, 1,349 of whom had a CT-confirmed ischemic stroke (2.34%).
The study group (ie, patients with ischemic stroke who were receiving disease-modifying therapy) included 126 patients (89 females), and the control group (ie, patients with ischemic stroke who had not received disease-modifying therapy) included 1,002 patients.
Patients not treated with disease-modifying therapy were approximately twice as likely to have an ischemic stroke, compared with patients treated with disease-modifying therapy (odds ratio = 1.91).
After controlling for covariates (eg, smoking, hypertension, diabetes, heart failure, atrial fibrillation, age, and sex), the likelihood of ischemic stroke remained higher in the untreated group.
“This study suggests that the early treatment of MS with disease-modifying therapies may reduce the risk of ischemic stroke in the MS population,” said Dr. Ikram and colleagues.
—Jake Remaly
CMSC looks to increase advocacy efforts to address looming concerns
As patients with multiple sclerosis and their caregivers face various challenges in the American health care system, the Consortium of Multiple Sclerosis Centers (CMSC) is re-energizing its focus on advocacy. The 2018 annual meeting in Nashville, Tenn., will feature programming designed to teach MS professionals and researchers how to speak up and let their voices be heard.
“CMSC has re-engaged in advocacy, in a more focused and energized way, because of mounting concerns that there is inadequate advocacy pressure on some of the critical issues negatively impacting the quality and comprehensive nature of MS care required of people living with MS,” said Lisa Taylor Skutnik, a physical therapist and chief operating officer of the CMSC. “Both people living with MS and the clinicians dedicated to treating them are increasingly frustrated and powerless in attempts to facilitate the right care and resources for people living with MS. Our members are facing significant barriers and obstacles to ensure timely and seamless comprehensive care.”
The development of quality measures in MS is also a “huge concern,” she said, referring to the federal government’s efforts to develop new ways to measure whether health professionals are providing high-quality care. Physicians have expressed widespread concern about the measures, which are being linked to reimbursement from Medicare and Medicaid.
Among the highlights of the CMSC meeting will be an educational session that “will focus on the available resources within the MS community for MS professionals and researchers to access advocacy efforts and get involved,” Ms. Skutnik said.
Another educational session “will focus on helping MS clinicians and researchers to understand all of the various stakeholders and their respective perspectives related to access to comprehensive care services for those living with MS,” such as pharmacy benefit managers and insurers, she said.
As patients with multiple sclerosis and their caregivers face various challenges in the American health care system, the Consortium of Multiple Sclerosis Centers (CMSC) is re-energizing its focus on advocacy. The 2018 annual meeting in Nashville, Tenn., will feature programming designed to teach MS professionals and researchers how to speak up and let their voices be heard.
“CMSC has re-engaged in advocacy, in a more focused and energized way, because of mounting concerns that there is inadequate advocacy pressure on some of the critical issues negatively impacting the quality and comprehensive nature of MS care required of people living with MS,” said Lisa Taylor Skutnik, a physical therapist and chief operating officer of the CMSC. “Both people living with MS and the clinicians dedicated to treating them are increasingly frustrated and powerless in attempts to facilitate the right care and resources for people living with MS. Our members are facing significant barriers and obstacles to ensure timely and seamless comprehensive care.”
The development of quality measures in MS is also a “huge concern,” she said, referring to the federal government’s efforts to develop new ways to measure whether health professionals are providing high-quality care. Physicians have expressed widespread concern about the measures, which are being linked to reimbursement from Medicare and Medicaid.
Among the highlights of the CMSC meeting will be an educational session that “will focus on the available resources within the MS community for MS professionals and researchers to access advocacy efforts and get involved,” Ms. Skutnik said.
Another educational session “will focus on helping MS clinicians and researchers to understand all of the various stakeholders and their respective perspectives related to access to comprehensive care services for those living with MS,” such as pharmacy benefit managers and insurers, she said.
As patients with multiple sclerosis and their caregivers face various challenges in the American health care system, the Consortium of Multiple Sclerosis Centers (CMSC) is re-energizing its focus on advocacy. The 2018 annual meeting in Nashville, Tenn., will feature programming designed to teach MS professionals and researchers how to speak up and let their voices be heard.
“CMSC has re-engaged in advocacy, in a more focused and energized way, because of mounting concerns that there is inadequate advocacy pressure on some of the critical issues negatively impacting the quality and comprehensive nature of MS care required of people living with MS,” said Lisa Taylor Skutnik, a physical therapist and chief operating officer of the CMSC. “Both people living with MS and the clinicians dedicated to treating them are increasingly frustrated and powerless in attempts to facilitate the right care and resources for people living with MS. Our members are facing significant barriers and obstacles to ensure timely and seamless comprehensive care.”
The development of quality measures in MS is also a “huge concern,” she said, referring to the federal government’s efforts to develop new ways to measure whether health professionals are providing high-quality care. Physicians have expressed widespread concern about the measures, which are being linked to reimbursement from Medicare and Medicaid.
Among the highlights of the CMSC meeting will be an educational session that “will focus on the available resources within the MS community for MS professionals and researchers to access advocacy efforts and get involved,” Ms. Skutnik said.
Another educational session “will focus on helping MS clinicians and researchers to understand all of the various stakeholders and their respective perspectives related to access to comprehensive care services for those living with MS,” such as pharmacy benefit managers and insurers, she said.
Neurology Board Review: Multiple Sclerosis
Click here to read Neurology Board Review: Multiple Sclerosis
Neurology Board Review: Multiple Sclerosis is a resource developed by leading clinical educators for studying for board certification and maintenance of certification exams.
After reading the article, Click Here to Access the Board Review Questions
About the Authors
Michael J. Bradshaw, MD
Clinical Fellow in Neurology
Partners Multiple Sclerosis Center
Brigham and Women’s Hospital
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Maria K. Houtchens, MD, MMSC
Director, Women’s Health Program
Partners Multiple Sclerosis Center
Brigham and Women’s Hospital
Harvard Medical School
Boston, Massachusetts
Click here to read Neurology Board Review: Multiple Sclerosis
After reading the article, Click Here to Access the Board Review Questions
Click here to read Neurology Board Review: Multiple Sclerosis
Neurology Board Review: Multiple Sclerosis is a resource developed by leading clinical educators for studying for board certification and maintenance of certification exams.
After reading the article, Click Here to Access the Board Review Questions
About the Authors
Michael J. Bradshaw, MD
Clinical Fellow in Neurology
Partners Multiple Sclerosis Center
Brigham and Women’s Hospital
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Maria K. Houtchens, MD, MMSC
Director, Women’s Health Program
Partners Multiple Sclerosis Center
Brigham and Women’s Hospital
Harvard Medical School
Boston, Massachusetts
Click here to read Neurology Board Review: Multiple Sclerosis
After reading the article, Click Here to Access the Board Review Questions
Click here to read Neurology Board Review: Multiple Sclerosis
Neurology Board Review: Multiple Sclerosis is a resource developed by leading clinical educators for studying for board certification and maintenance of certification exams.
After reading the article, Click Here to Access the Board Review Questions
About the Authors
Michael J. Bradshaw, MD
Clinical Fellow in Neurology
Partners Multiple Sclerosis Center
Brigham and Women’s Hospital
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Maria K. Houtchens, MD, MMSC
Director, Women’s Health Program
Partners Multiple Sclerosis Center
Brigham and Women’s Hospital
Harvard Medical School
Boston, Massachusetts
Click here to read Neurology Board Review: Multiple Sclerosis
After reading the article, Click Here to Access the Board Review Questions
Rehabilitation in MS is hot topic at CMSC 2018
This year’s annual meeting of the Consortium of Multiple Sclerosis Centers in Nashville, Tenn., will feature an intense focus on rehabilitation in MS. The topic is often a priority for patients but not necessarily at top of mind for health care providers, said rehabilitation therapist Patty Bobryk, secretary of the CMSC.
“This year, some of the Rehab Track topics include addressing respiratory issues in MS, exploring the impact of visual impairments on rehab, and recommending the proper orthotics, as well as discussing treatments that focus on mind-body understanding,” said Ms. Bobryk of MS Comprehensive Care Center of Central Florida, Orlando. She serves as cochair of the International Organization of MS Rehabilitation Therapists.
Rehabilitation in MS is a controversial topic. Two years ago, the CMSC endorsed a statement criticizing a 2015 report by the American Academy of Neurology that found limited evidence supporting MS rehabilitation (Neurology. 2015 Nov 24;85[21]:1896-903). The statement, also supported by the International Organization of MS Nurses and International Organization of MS Rehabilitation Therapists, declared that the AAN report “presents an incomplete review of the evidence published” (Neurol Clin Pract. 2016 Dec;6[6]:475-9).
However, the statement acknowledged that “larger studies with better research methodologies and higher-quality evidence are needed in rehabilitation.”
More recently, a 2017 systematic review of systematic reviews of rehabilitation in MS found that “strong” evidence only exists “for physical therapy for improved activity and participation, and for exercise-based educational programs for the reduction of patient-reported fatigue.” The review of reviews also found there’s “ ‘moderate’ evidence for multidisciplinary rehabilitation for longer-term gains at the levels of activity (disability) and participation, for cognitive-behavior therapy for the treatment of depression, and for information-provision interventions for improved patient knowledge” (Arch Phys Med Rehabil. 2017 Feb;98[2]:353-67).
In an interview, Ms. Bobryk said the MS rehabilitation community is evolving toward “a better understanding of neuroplasticity and the impact that rehab can have on maintaining and improving functional skills.”
In addition, she said, “more emphasis is being placed on early intervention and preventing the secondary effects of the disease versus providing only compensatory strategies.”
Highlights of this year’s rehab sessions at the CMSC conference include a 3-hour course on imbalance in MS that will “provide an intensive review of the anatomy of the balance system and educate the audience on evaluation and treatment interventions specific to retraining the balance system,” Ms. Bobryk said.
Another highlight: A half-day course that will “provide the rationale for including rehabilitation in a comprehensive model of care for people with severe MS,” she said. “Unique interventions such as the use of functional electrical stimulation cycling and body weight-supported treadmill training will be discussed.”
In the big picture, “clinicians who are working in the field of MS realize the benefits of rehab, but more education is needed to spread the word to the broader scope of health care providers,” Ms. Bobryk said. “Patients are often the ones that bring up rehab to their physicians to initiate a referral.”
This year’s annual meeting of the Consortium of Multiple Sclerosis Centers in Nashville, Tenn., will feature an intense focus on rehabilitation in MS. The topic is often a priority for patients but not necessarily at top of mind for health care providers, said rehabilitation therapist Patty Bobryk, secretary of the CMSC.
“This year, some of the Rehab Track topics include addressing respiratory issues in MS, exploring the impact of visual impairments on rehab, and recommending the proper orthotics, as well as discussing treatments that focus on mind-body understanding,” said Ms. Bobryk of MS Comprehensive Care Center of Central Florida, Orlando. She serves as cochair of the International Organization of MS Rehabilitation Therapists.
Rehabilitation in MS is a controversial topic. Two years ago, the CMSC endorsed a statement criticizing a 2015 report by the American Academy of Neurology that found limited evidence supporting MS rehabilitation (Neurology. 2015 Nov 24;85[21]:1896-903). The statement, also supported by the International Organization of MS Nurses and International Organization of MS Rehabilitation Therapists, declared that the AAN report “presents an incomplete review of the evidence published” (Neurol Clin Pract. 2016 Dec;6[6]:475-9).
However, the statement acknowledged that “larger studies with better research methodologies and higher-quality evidence are needed in rehabilitation.”
More recently, a 2017 systematic review of systematic reviews of rehabilitation in MS found that “strong” evidence only exists “for physical therapy for improved activity and participation, and for exercise-based educational programs for the reduction of patient-reported fatigue.” The review of reviews also found there’s “ ‘moderate’ evidence for multidisciplinary rehabilitation for longer-term gains at the levels of activity (disability) and participation, for cognitive-behavior therapy for the treatment of depression, and for information-provision interventions for improved patient knowledge” (Arch Phys Med Rehabil. 2017 Feb;98[2]:353-67).
In an interview, Ms. Bobryk said the MS rehabilitation community is evolving toward “a better understanding of neuroplasticity and the impact that rehab can have on maintaining and improving functional skills.”
In addition, she said, “more emphasis is being placed on early intervention and preventing the secondary effects of the disease versus providing only compensatory strategies.”
Highlights of this year’s rehab sessions at the CMSC conference include a 3-hour course on imbalance in MS that will “provide an intensive review of the anatomy of the balance system and educate the audience on evaluation and treatment interventions specific to retraining the balance system,” Ms. Bobryk said.
Another highlight: A half-day course that will “provide the rationale for including rehabilitation in a comprehensive model of care for people with severe MS,” she said. “Unique interventions such as the use of functional electrical stimulation cycling and body weight-supported treadmill training will be discussed.”
In the big picture, “clinicians who are working in the field of MS realize the benefits of rehab, but more education is needed to spread the word to the broader scope of health care providers,” Ms. Bobryk said. “Patients are often the ones that bring up rehab to their physicians to initiate a referral.”
This year’s annual meeting of the Consortium of Multiple Sclerosis Centers in Nashville, Tenn., will feature an intense focus on rehabilitation in MS. The topic is often a priority for patients but not necessarily at top of mind for health care providers, said rehabilitation therapist Patty Bobryk, secretary of the CMSC.
“This year, some of the Rehab Track topics include addressing respiratory issues in MS, exploring the impact of visual impairments on rehab, and recommending the proper orthotics, as well as discussing treatments that focus on mind-body understanding,” said Ms. Bobryk of MS Comprehensive Care Center of Central Florida, Orlando. She serves as cochair of the International Organization of MS Rehabilitation Therapists.
Rehabilitation in MS is a controversial topic. Two years ago, the CMSC endorsed a statement criticizing a 2015 report by the American Academy of Neurology that found limited evidence supporting MS rehabilitation (Neurology. 2015 Nov 24;85[21]:1896-903). The statement, also supported by the International Organization of MS Nurses and International Organization of MS Rehabilitation Therapists, declared that the AAN report “presents an incomplete review of the evidence published” (Neurol Clin Pract. 2016 Dec;6[6]:475-9).
However, the statement acknowledged that “larger studies with better research methodologies and higher-quality evidence are needed in rehabilitation.”
More recently, a 2017 systematic review of systematic reviews of rehabilitation in MS found that “strong” evidence only exists “for physical therapy for improved activity and participation, and for exercise-based educational programs for the reduction of patient-reported fatigue.” The review of reviews also found there’s “ ‘moderate’ evidence for multidisciplinary rehabilitation for longer-term gains at the levels of activity (disability) and participation, for cognitive-behavior therapy for the treatment of depression, and for information-provision interventions for improved patient knowledge” (Arch Phys Med Rehabil. 2017 Feb;98[2]:353-67).
In an interview, Ms. Bobryk said the MS rehabilitation community is evolving toward “a better understanding of neuroplasticity and the impact that rehab can have on maintaining and improving functional skills.”
In addition, she said, “more emphasis is being placed on early intervention and preventing the secondary effects of the disease versus providing only compensatory strategies.”
Highlights of this year’s rehab sessions at the CMSC conference include a 3-hour course on imbalance in MS that will “provide an intensive review of the anatomy of the balance system and educate the audience on evaluation and treatment interventions specific to retraining the balance system,” Ms. Bobryk said.
Another highlight: A half-day course that will “provide the rationale for including rehabilitation in a comprehensive model of care for people with severe MS,” she said. “Unique interventions such as the use of functional electrical stimulation cycling and body weight-supported treadmill training will be discussed.”
In the big picture, “clinicians who are working in the field of MS realize the benefits of rehab, but more education is needed to spread the word to the broader scope of health care providers,” Ms. Bobryk said. “Patients are often the ones that bring up rehab to their physicians to initiate a referral.”
Wide variety of MS topics on tap at CMSC 2018
More than 2,000 members of the multiple sclerosis care, advocacy, research, and patient communities will gather in Nashville, Tenn., May 30–June 2 for the annual meeting of the Consortium of Multiple Sclerosis Centers.
Dozens of topics will be discussed, ranging from complementary/alternative therapies, ethics, and neuropsychiatry to neuroimmunology and disease models, relapse management, and self-care. Clinicians also will tackle sensitive topics such as suicide, depression, and cognitive impairment.
“Accredited continuing education will be offered for MDs, registered nurses, pharmacists, occupational therapists, physical therapists, social workers, and psychologists,” said Gary Cutter, PhD, president of the CMSC. “Our offerings include beginner courses, advanced science sessions, rehab and mental health tracks, platform and poster sessions, and roundtables.”
“We’ll discuss meds for progressive forms of MS as well as targeted therapies based on new information from genetics,” Dr. Cutter said. Participants will also gain insight from registries and other data sources, he added.
Lecture topics will include the use of computerized screening for cognitive dysfunction in the MS clinic and new research into MS pathology.
Other sessions will explore the use of cannabis, infusion therapies, respiratory enhancement, and a new class of medications for blocking lipid metabolism. Rehabilitation will also be a major focus.
One session will examine MS in patients before conception, during pregnancy, and in the postpartum period. Another session will explore suicide in MS and discuss how clinics can identify and help patients at risk.
The annual CMSC conference stands apart because it’s a “relatively unique meeting where the entire MS treatment team, researchers, and persons with MS can interact and discuss the complex issues in MS care,” Dr. Cutter said. “Much of this takes place outside of the formal program but can still have major impact on all of us. The enthusiasm of the young attendees is always amazing. They are supported, involved, and encouraged.”
More than 2,000 members of the multiple sclerosis care, advocacy, research, and patient communities will gather in Nashville, Tenn., May 30–June 2 for the annual meeting of the Consortium of Multiple Sclerosis Centers.
Dozens of topics will be discussed, ranging from complementary/alternative therapies, ethics, and neuropsychiatry to neuroimmunology and disease models, relapse management, and self-care. Clinicians also will tackle sensitive topics such as suicide, depression, and cognitive impairment.
“Accredited continuing education will be offered for MDs, registered nurses, pharmacists, occupational therapists, physical therapists, social workers, and psychologists,” said Gary Cutter, PhD, president of the CMSC. “Our offerings include beginner courses, advanced science sessions, rehab and mental health tracks, platform and poster sessions, and roundtables.”
“We’ll discuss meds for progressive forms of MS as well as targeted therapies based on new information from genetics,” Dr. Cutter said. Participants will also gain insight from registries and other data sources, he added.
Lecture topics will include the use of computerized screening for cognitive dysfunction in the MS clinic and new research into MS pathology.
Other sessions will explore the use of cannabis, infusion therapies, respiratory enhancement, and a new class of medications for blocking lipid metabolism. Rehabilitation will also be a major focus.
One session will examine MS in patients before conception, during pregnancy, and in the postpartum period. Another session will explore suicide in MS and discuss how clinics can identify and help patients at risk.
The annual CMSC conference stands apart because it’s a “relatively unique meeting where the entire MS treatment team, researchers, and persons with MS can interact and discuss the complex issues in MS care,” Dr. Cutter said. “Much of this takes place outside of the formal program but can still have major impact on all of us. The enthusiasm of the young attendees is always amazing. They are supported, involved, and encouraged.”
More than 2,000 members of the multiple sclerosis care, advocacy, research, and patient communities will gather in Nashville, Tenn., May 30–June 2 for the annual meeting of the Consortium of Multiple Sclerosis Centers.
Dozens of topics will be discussed, ranging from complementary/alternative therapies, ethics, and neuropsychiatry to neuroimmunology and disease models, relapse management, and self-care. Clinicians also will tackle sensitive topics such as suicide, depression, and cognitive impairment.
“Accredited continuing education will be offered for MDs, registered nurses, pharmacists, occupational therapists, physical therapists, social workers, and psychologists,” said Gary Cutter, PhD, president of the CMSC. “Our offerings include beginner courses, advanced science sessions, rehab and mental health tracks, platform and poster sessions, and roundtables.”
“We’ll discuss meds for progressive forms of MS as well as targeted therapies based on new information from genetics,” Dr. Cutter said. Participants will also gain insight from registries and other data sources, he added.
Lecture topics will include the use of computerized screening for cognitive dysfunction in the MS clinic and new research into MS pathology.
Other sessions will explore the use of cannabis, infusion therapies, respiratory enhancement, and a new class of medications for blocking lipid metabolism. Rehabilitation will also be a major focus.
One session will examine MS in patients before conception, during pregnancy, and in the postpartum period. Another session will explore suicide in MS and discuss how clinics can identify and help patients at risk.
The annual CMSC conference stands apart because it’s a “relatively unique meeting where the entire MS treatment team, researchers, and persons with MS can interact and discuss the complex issues in MS care,” Dr. Cutter said. “Much of this takes place outside of the formal program but can still have major impact on all of us. The enthusiasm of the young attendees is always amazing. They are supported, involved, and encouraged.”
FDA Updates
First Anti-CGRP Monoclonal Antibody Gains FDA Approval
The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third stu
FDA Approves Gilenya for Pediatric Use
The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.
FDA Approves Treatment for CIDP
The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.
DBS Device Approved for Refractory Epilepsy
The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.
FDA Issues Warning About Lamictal
The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.
First Anti-CGRP Monoclonal Antibody Gains FDA Approval
The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third stu
FDA Approves Gilenya for Pediatric Use
The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.
FDA Approves Treatment for CIDP
The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.
DBS Device Approved for Refractory Epilepsy
The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.
FDA Issues Warning About Lamictal
The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.
First Anti-CGRP Monoclonal Antibody Gains FDA Approval
The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third stu
FDA Approves Gilenya for Pediatric Use
The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.
FDA Approves Treatment for CIDP
The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.
DBS Device Approved for Refractory Epilepsy
The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.
FDA Issues Warning About Lamictal
The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.
Ocrelizumab safety update: Encouraging rates of serious infection, malignancy
LOS ANGELES – No new safety signals have emerged in multiple sclerosis patients treated with ocrelizumab, according to ongoing follow-up and postmarketing surveillance.
As of September 2017, patients with relapsing or primary progressive MS who were part of the pivotal OPERA I and II and ORATORIO trials – including phases 2 and 3 and open-label extensions – as well as an all-exposure population that included patients from prior studies, had nearly 9,500 patient-years of exposure to ocrelizumab (Ocrevus), a humanized anti-CD20 monoclonal antibody. The all-exposure population contributed about 1,500 of those patient-years, Stephen Hauser, MD, reported at the annual meeting of the American Academy of Neurology.
Postmarketing experience in approximately 37,000 treated patients with an additional 14,000 patient-years shows a fatality rate of 0.28/100 patient-years (49 fatalities) as of March 2018, he said.
“If one compares this to at least two reports of epidemiologic mortality estimates in MS, this is in line with – and in fact a little bit lower than – those estimates that range between 0.37 and 0.9, compared with 0.28,” he said. “So ... the updated safety profile in this all-exposure ocrelizumab population was generally consistent with what was seen during the controlled treatment period, and rates of serious infections fluctuated over time without any sustained increase.”
Only one serious opportunistic infection (Pasteurella) occurred in the controlled trials, and three more (two varicella zoster, one herpes simplex) occurred during open-marketing experience.
The rate of malignancies has been very encouraging, as well, as it appears to continue to align with population expectations, Dr. Hauser said.
Trial participants received 600-mg doses intravenously every 24 weeks in all three trials; in OPERA I/II, they received 96 weeks of treatment with the first dose given as two 300-mg infusions split by 14 days, and, in ORATORIO, they received at least 120 weeks of treatment with all doses split, Dr. Hauser said.
In the phase 2 study, they received split doses of 600-mg or 2,000-mg infusions through week 24; then through week 96, they received either 600-mg or 1,000-mg doses; those receiving 600 mg included those who started at that dose and those who received placebo or interferon beta-1a 30 mcg, and those receiving 1,000 mg were those who started on ocrelizumab at 2,000 mg.
The comparators were placebo in the ORATORIO and phase 2 trials, and interferon beta-1a given at a dose of 44 mcg subcutaneously three times weekly (OPERA I and II) or 30 mcg intramuscularly each week in the phase 2 trial.
All patients were offered enrollment into open-label extension studies, and “there was rather massive interest in joining the open-label extension and continuing open-label extension in both trials,” he said.
“And earlier here at the AAN [meeting] we presented the clinical efficacy data from the open-label extension, now 2 years completed – so 4 years from onset of the study – in patients who received ocrelizumab continuously for [relapsing-remitting] MS during that time period, or who switched from three-times-weekly interferon beta-1a to ocrelizumab ... and the data continue to show the positive outcomes reported in the original trials,” he added.
Further, follow-up data on MRI outcomes from the open-label extensions demonstrate that the effects on focal disease activity and on progression persists and is durable with ongoing treatment, he noted.
“In conclusion, there is no pattern of serious infections or malignancies that has emerged thus far with increased exposure, but obviously long-term follow-up and postmarketing requirement studies are needed to monitor long-term patient safety and rare events that couldn’t be captured here,” he said.
This study was sponsored by F. Hoffmann-La Roche. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Symbiotix, Annexon Biosciences, Bionure, Molecular Stethoscope, and for serving on the Board of Directors of Neurona Therapeutics.
SOURCE: Hauser S et al. Neurology. 2018 Apr 9;(15 Suppl.):S36.001.
LOS ANGELES – No new safety signals have emerged in multiple sclerosis patients treated with ocrelizumab, according to ongoing follow-up and postmarketing surveillance.
As of September 2017, patients with relapsing or primary progressive MS who were part of the pivotal OPERA I and II and ORATORIO trials – including phases 2 and 3 and open-label extensions – as well as an all-exposure population that included patients from prior studies, had nearly 9,500 patient-years of exposure to ocrelizumab (Ocrevus), a humanized anti-CD20 monoclonal antibody. The all-exposure population contributed about 1,500 of those patient-years, Stephen Hauser, MD, reported at the annual meeting of the American Academy of Neurology.
Postmarketing experience in approximately 37,000 treated patients with an additional 14,000 patient-years shows a fatality rate of 0.28/100 patient-years (49 fatalities) as of March 2018, he said.
“If one compares this to at least two reports of epidemiologic mortality estimates in MS, this is in line with – and in fact a little bit lower than – those estimates that range between 0.37 and 0.9, compared with 0.28,” he said. “So ... the updated safety profile in this all-exposure ocrelizumab population was generally consistent with what was seen during the controlled treatment period, and rates of serious infections fluctuated over time without any sustained increase.”
Only one serious opportunistic infection (Pasteurella) occurred in the controlled trials, and three more (two varicella zoster, one herpes simplex) occurred during open-marketing experience.
The rate of malignancies has been very encouraging, as well, as it appears to continue to align with population expectations, Dr. Hauser said.
Trial participants received 600-mg doses intravenously every 24 weeks in all three trials; in OPERA I/II, they received 96 weeks of treatment with the first dose given as two 300-mg infusions split by 14 days, and, in ORATORIO, they received at least 120 weeks of treatment with all doses split, Dr. Hauser said.
In the phase 2 study, they received split doses of 600-mg or 2,000-mg infusions through week 24; then through week 96, they received either 600-mg or 1,000-mg doses; those receiving 600 mg included those who started at that dose and those who received placebo or interferon beta-1a 30 mcg, and those receiving 1,000 mg were those who started on ocrelizumab at 2,000 mg.
The comparators were placebo in the ORATORIO and phase 2 trials, and interferon beta-1a given at a dose of 44 mcg subcutaneously three times weekly (OPERA I and II) or 30 mcg intramuscularly each week in the phase 2 trial.
All patients were offered enrollment into open-label extension studies, and “there was rather massive interest in joining the open-label extension and continuing open-label extension in both trials,” he said.
“And earlier here at the AAN [meeting] we presented the clinical efficacy data from the open-label extension, now 2 years completed – so 4 years from onset of the study – in patients who received ocrelizumab continuously for [relapsing-remitting] MS during that time period, or who switched from three-times-weekly interferon beta-1a to ocrelizumab ... and the data continue to show the positive outcomes reported in the original trials,” he added.
Further, follow-up data on MRI outcomes from the open-label extensions demonstrate that the effects on focal disease activity and on progression persists and is durable with ongoing treatment, he noted.
“In conclusion, there is no pattern of serious infections or malignancies that has emerged thus far with increased exposure, but obviously long-term follow-up and postmarketing requirement studies are needed to monitor long-term patient safety and rare events that couldn’t be captured here,” he said.
This study was sponsored by F. Hoffmann-La Roche. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Symbiotix, Annexon Biosciences, Bionure, Molecular Stethoscope, and for serving on the Board of Directors of Neurona Therapeutics.
SOURCE: Hauser S et al. Neurology. 2018 Apr 9;(15 Suppl.):S36.001.
LOS ANGELES – No new safety signals have emerged in multiple sclerosis patients treated with ocrelizumab, according to ongoing follow-up and postmarketing surveillance.
As of September 2017, patients with relapsing or primary progressive MS who were part of the pivotal OPERA I and II and ORATORIO trials – including phases 2 and 3 and open-label extensions – as well as an all-exposure population that included patients from prior studies, had nearly 9,500 patient-years of exposure to ocrelizumab (Ocrevus), a humanized anti-CD20 monoclonal antibody. The all-exposure population contributed about 1,500 of those patient-years, Stephen Hauser, MD, reported at the annual meeting of the American Academy of Neurology.
Postmarketing experience in approximately 37,000 treated patients with an additional 14,000 patient-years shows a fatality rate of 0.28/100 patient-years (49 fatalities) as of March 2018, he said.
“If one compares this to at least two reports of epidemiologic mortality estimates in MS, this is in line with – and in fact a little bit lower than – those estimates that range between 0.37 and 0.9, compared with 0.28,” he said. “So ... the updated safety profile in this all-exposure ocrelizumab population was generally consistent with what was seen during the controlled treatment period, and rates of serious infections fluctuated over time without any sustained increase.”
Only one serious opportunistic infection (Pasteurella) occurred in the controlled trials, and three more (two varicella zoster, one herpes simplex) occurred during open-marketing experience.
The rate of malignancies has been very encouraging, as well, as it appears to continue to align with population expectations, Dr. Hauser said.
Trial participants received 600-mg doses intravenously every 24 weeks in all three trials; in OPERA I/II, they received 96 weeks of treatment with the first dose given as two 300-mg infusions split by 14 days, and, in ORATORIO, they received at least 120 weeks of treatment with all doses split, Dr. Hauser said.
In the phase 2 study, they received split doses of 600-mg or 2,000-mg infusions through week 24; then through week 96, they received either 600-mg or 1,000-mg doses; those receiving 600 mg included those who started at that dose and those who received placebo or interferon beta-1a 30 mcg, and those receiving 1,000 mg were those who started on ocrelizumab at 2,000 mg.
The comparators were placebo in the ORATORIO and phase 2 trials, and interferon beta-1a given at a dose of 44 mcg subcutaneously three times weekly (OPERA I and II) or 30 mcg intramuscularly each week in the phase 2 trial.
All patients were offered enrollment into open-label extension studies, and “there was rather massive interest in joining the open-label extension and continuing open-label extension in both trials,” he said.
“And earlier here at the AAN [meeting] we presented the clinical efficacy data from the open-label extension, now 2 years completed – so 4 years from onset of the study – in patients who received ocrelizumab continuously for [relapsing-remitting] MS during that time period, or who switched from three-times-weekly interferon beta-1a to ocrelizumab ... and the data continue to show the positive outcomes reported in the original trials,” he added.
Further, follow-up data on MRI outcomes from the open-label extensions demonstrate that the effects on focal disease activity and on progression persists and is durable with ongoing treatment, he noted.
“In conclusion, there is no pattern of serious infections or malignancies that has emerged thus far with increased exposure, but obviously long-term follow-up and postmarketing requirement studies are needed to monitor long-term patient safety and rare events that couldn’t be captured here,” he said.
This study was sponsored by F. Hoffmann-La Roche. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Symbiotix, Annexon Biosciences, Bionure, Molecular Stethoscope, and for serving on the Board of Directors of Neurona Therapeutics.
SOURCE: Hauser S et al. Neurology. 2018 Apr 9;(15 Suppl.):S36.001.
REPORTING FROM AAN 2018
Key clinical point: Follow-up and postmarketing surveillance show no new safety signals with ocrelizumab.
Major finding: The fatality rate was 0.28/100 patient-years as of March 2018.
Study details: Follow-up of patients with nearly 9,500 patient-years of experience with ocrelizumab and postmarketing surveillance in patients with more than 14,000 patient-years of experience.
Disclosures: This study was sponsored by F. Hoffmann-La Roche. Dr. Hauser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Symbiotix, Annexon Biosciences, Bionure, Molecular Stethoscope, and for serving on the board of directors of Neurona Therapeutics.
Source: Hauser S et al. Neurology. 2018 Apr 9;(15 Suppl.):S36.001.
FDA expands fingolimod's indications to treat relapsing MS in pediatric patients
Pediatric patients with
The Food and Drug Administration approved on May 11 an expanded indication of the drug to allow it to be used to treat relapsing MS in children and adolescents age 10 and older. Gilenya was first approved by FDA to treat adults with relapsing MS in 2010.
“For the first time, we have an FDA-approved treatment specifically for children and adolescents with multiple sclerosis,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, said in a statement. “This represents an important and needed advance in the care of pediatric patients with multiple sclerosis.”
Side effects for fingolimod in pediatric trial participants were similar to those experienced in adults, the most common of which include headache, liver enzyme elevation, diarrhea, cough, flu, sinusitis, back pain, abdominal pain, and pain in extremities. The drug must be dispensed with a medication guide that describes the product’s more serious risks.
The FDA, which granted the product a priority review and breakthrough designation for this indication, noted that 2%-5% of people with MS have symptoms onset before age 18 and suggested that 8,000-10,000 children and adolescents in the United States suffer from the disease.
The clinical trial evaluating the drug included 214 patients aged 10-17 years and compared fingolimod with interferon beta-1a. In that study, the FDA stated that 86% of patients receiving fingolimod remained relapse-free after 24 months of treatment, compared with 46% of those treated with interferon beta-1a.
Pediatric patients with
The Food and Drug Administration approved on May 11 an expanded indication of the drug to allow it to be used to treat relapsing MS in children and adolescents age 10 and older. Gilenya was first approved by FDA to treat adults with relapsing MS in 2010.
“For the first time, we have an FDA-approved treatment specifically for children and adolescents with multiple sclerosis,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, said in a statement. “This represents an important and needed advance in the care of pediatric patients with multiple sclerosis.”
Side effects for fingolimod in pediatric trial participants were similar to those experienced in adults, the most common of which include headache, liver enzyme elevation, diarrhea, cough, flu, sinusitis, back pain, abdominal pain, and pain in extremities. The drug must be dispensed with a medication guide that describes the product’s more serious risks.
The FDA, which granted the product a priority review and breakthrough designation for this indication, noted that 2%-5% of people with MS have symptoms onset before age 18 and suggested that 8,000-10,000 children and adolescents in the United States suffer from the disease.
The clinical trial evaluating the drug included 214 patients aged 10-17 years and compared fingolimod with interferon beta-1a. In that study, the FDA stated that 86% of patients receiving fingolimod remained relapse-free after 24 months of treatment, compared with 46% of those treated with interferon beta-1a.
Pediatric patients with
The Food and Drug Administration approved on May 11 an expanded indication of the drug to allow it to be used to treat relapsing MS in children and adolescents age 10 and older. Gilenya was first approved by FDA to treat adults with relapsing MS in 2010.
“For the first time, we have an FDA-approved treatment specifically for children and adolescents with multiple sclerosis,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, said in a statement. “This represents an important and needed advance in the care of pediatric patients with multiple sclerosis.”
Side effects for fingolimod in pediatric trial participants were similar to those experienced in adults, the most common of which include headache, liver enzyme elevation, diarrhea, cough, flu, sinusitis, back pain, abdominal pain, and pain in extremities. The drug must be dispensed with a medication guide that describes the product’s more serious risks.
The FDA, which granted the product a priority review and breakthrough designation for this indication, noted that 2%-5% of people with MS have symptoms onset before age 18 and suggested that 8,000-10,000 children and adolescents in the United States suffer from the disease.
The clinical trial evaluating the drug included 214 patients aged 10-17 years and compared fingolimod with interferon beta-1a. In that study, the FDA stated that 86% of patients receiving fingolimod remained relapse-free after 24 months of treatment, compared with 46% of those treated with interferon beta-1a.