Multiple Sclerosis Hub

NEW ORLEANS—A diet high in fruits, vegetables, legumes, and whole grains and low in sugar and red meat is associated with less disability and fewer depressive symptoms in patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Our findings suggest that people with MS who have a healthier diet have less disability, and that a generally healthy lifestyle is associated with a lower burden of severe depression, pain, fatigue, and cognitive problems. Therefore, modifying diet may offer a way of improving symptoms,” said Ruth Ann Marrie, MD, PhD, Associate Professor of Neurology and Director of the MS Clinic at the University of Manitoba in Winnipeg, Canada.

Many patients with MS ask whether their diet could influence their disease status. To address this question, Dr. Marrie and colleagues assessed the association between overall diet quality and disability and physical and mental functioning in a large cohort of people with MS. They conducted a cross-sectional study of North American Research Committee on MS (NARCOMS) registry participants who had completed a dietary screener questionnaire. The questionnaire, created by the National Health and Nutrition Examination Survey, provides an assessment of diet composition when full information on diet is unavailable. The survey estimates intake of fruits, vegetables and legumes, whole grains, added sugars, and red and processed meats.

The researchers constructed an overall diet-quality score based on responses to the questionnaire and assigned participants to sex-specific quintiles of each of the questionnaire’s five food groups. They then assigned scores for fruits, vegetables, legumes, and whole grains based on the patient’s quintile ranking. The investigators inverted scores for red and processed meats and added sugar. The researchers summed individual food-group scores to obtain an overall diet score, ranging from 4 (poor quality) to 20 (high quality).

Dr. Marrie and colleagues assessed the association between diet quality and disability status (using the Patient-Determined Disease Steps) and mental and physical functioning (ie, depression, fatigue, cognition, mobility, vision, pain, spasticity, tremor, and sensory function) using proportional odds models adjusting for age, gender, income, BMI, smoking status, and disease duration.

In all, 7,418 responders had an average quality-diet score of 11.9. Patients with higher scores tended to be older, leaner, and nonsmokers. People with diet-quality scores in the top quintile had lower levels of disability and lower depression scores. Diet-quality scores were not associated with other physical or mental functioning scores, however.

A lack of details about potentially important dietary factors, such as types of fat, is one limitation of the study, said Dr. Marrie.

“While our study does not prove that diet change will improve symptoms, a high-quality diet that emphasizes intake of fruits, vegetables, and whole grains, and lower intake of red meat, can be encouraged, given the known benefits for general health,” said Dr. Marrie. “Future studies should look at the relationship between diet and disability, as well as symptoms over time, so that we can establish whether changing diet will improve outcomes in MS. These studies should also look at diet in more detail.”

The National MS Society supported this study.

—Erica Tricarico

NEW ORLEANS—A diet high in fruits, vegetables, legumes, and whole grains and low in sugar and red meat is associated with less disability and fewer depressive symptoms in patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Our findings suggest that people with MS who have a healthier diet have less disability, and that a generally healthy lifestyle is associated with a lower burden of severe depression, pain, fatigue, and cognitive problems. Therefore, modifying diet may offer a way of improving symptoms,” said Ruth Ann Marrie, MD, PhD, Associate Professor of Neurology and Director of the MS Clinic at the University of Manitoba in Winnipeg, Canada.

Many patients with MS ask whether their diet could influence their disease status. To address this question, Dr. Marrie and colleagues assessed the association between overall diet quality and disability and physical and mental functioning in a large cohort of people with MS. They conducted a cross-sectional study of North American Research Committee on MS (NARCOMS) registry participants who had completed a dietary screener questionnaire. The questionnaire, created by the National Health and Nutrition Examination Survey, provides an assessment of diet composition when full information on diet is unavailable. The survey estimates intake of fruits, vegetables and legumes, whole grains, added sugars, and red and processed meats.

The researchers constructed an overall diet-quality score based on responses to the questionnaire and assigned participants to sex-specific quintiles of each of the questionnaire’s five food groups. They then assigned scores for fruits, vegetables, legumes, and whole grains based on the patient’s quintile ranking. The investigators inverted scores for red and processed meats and added sugar. The researchers summed individual food-group scores to obtain an overall diet score, ranging from 4 (poor quality) to 20 (high quality).

Dr. Marrie and colleagues assessed the association between diet quality and disability status (using the Patient-Determined Disease Steps) and mental and physical functioning (ie, depression, fatigue, cognition, mobility, vision, pain, spasticity, tremor, and sensory function) using proportional odds models adjusting for age, gender, income, BMI, smoking status, and disease duration.

In all, 7,418 responders had an average quality-diet score of 11.9. Patients with higher scores tended to be older, leaner, and nonsmokers. People with diet-quality scores in the top quintile had lower levels of disability and lower depression scores. Diet-quality scores were not associated with other physical or mental functioning scores, however.

A lack of details about potentially important dietary factors, such as types of fat, is one limitation of the study, said Dr. Marrie.

“While our study does not prove that diet change will improve symptoms, a high-quality diet that emphasizes intake of fruits, vegetables, and whole grains, and lower intake of red meat, can be encouraged, given the known benefits for general health,” said Dr. Marrie. “Future studies should look at the relationship between diet and disability, as well as symptoms over time, so that we can establish whether changing diet will improve outcomes in MS. These studies should also look at diet in more detail.”

The National MS Society supported this study.

—Erica Tricarico

NEW ORLEANS—A diet high in fruits, vegetables, legumes, and whole grains and low in sugar and red meat is associated with less disability and fewer depressive symptoms in patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Our findings suggest that people with MS who have a healthier diet have less disability, and that a generally healthy lifestyle is associated with a lower burden of severe depression, pain, fatigue, and cognitive problems. Therefore, modifying diet may offer a way of improving symptoms,” said Ruth Ann Marrie, MD, PhD, Associate Professor of Neurology and Director of the MS Clinic at the University of Manitoba in Winnipeg, Canada.

Many patients with MS ask whether their diet could influence their disease status. To address this question, Dr. Marrie and colleagues assessed the association between overall diet quality and disability and physical and mental functioning in a large cohort of people with MS. They conducted a cross-sectional study of North American Research Committee on MS (NARCOMS) registry participants who had completed a dietary screener questionnaire. The questionnaire, created by the National Health and Nutrition Examination Survey, provides an assessment of diet composition when full information on diet is unavailable. The survey estimates intake of fruits, vegetables and legumes, whole grains, added sugars, and red and processed meats.

The researchers constructed an overall diet-quality score based on responses to the questionnaire and assigned participants to sex-specific quintiles of each of the questionnaire’s five food groups. They then assigned scores for fruits, vegetables, legumes, and whole grains based on the patient’s quintile ranking. The investigators inverted scores for red and processed meats and added sugar. The researchers summed individual food-group scores to obtain an overall diet score, ranging from 4 (poor quality) to 20 (high quality).

Dr. Marrie and colleagues assessed the association between diet quality and disability status (using the Patient-Determined Disease Steps) and mental and physical functioning (ie, depression, fatigue, cognition, mobility, vision, pain, spasticity, tremor, and sensory function) using proportional odds models adjusting for age, gender, income, BMI, smoking status, and disease duration.

In all, 7,418 responders had an average quality-diet score of 11.9. Patients with higher scores tended to be older, leaner, and nonsmokers. People with diet-quality scores in the top quintile had lower levels of disability and lower depression scores. Diet-quality scores were not associated with other physical or mental functioning scores, however.

A lack of details about potentially important dietary factors, such as types of fat, is one limitation of the study, said Dr. Marrie.

“While our study does not prove that diet change will improve symptoms, a high-quality diet that emphasizes intake of fruits, vegetables, and whole grains, and lower intake of red meat, can be encouraged, given the known benefits for general health,” said Dr. Marrie. “Future studies should look at the relationship between diet and disability, as well as symptoms over time, so that we can establish whether changing diet will improve outcomes in MS. These studies should also look at diet in more detail.”

The National MS Society supported this study.

—Erica Tricarico

NEW ORLEANS—Older adults with multiple sclerosis (MS) who engaged more in light physical activity demonstrated better physical function independent of sedentary behavior and moderate-to-vigorous activity, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Such results might underscore light physical activity as a suitable target of future rehabilitative interventions for improving physical function in older adults with MS,” said Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham.

Rate and pattern of participation in physical activity and sedentary behavior might be associated with a reduction of physical function among older adults with MS. Ms. Cederberg conducted a study that examined the associations among levels of light and moderate-to-vigorous physical activity, sedentary behavior, and physical function in older adults with MS.

Ms. Cederberg’s study sample included 40 older adults with MS with a median age of 60. Participants wore an accelerometer during the waking hours of a seven-day period. In addition, Ms. Cederberg used cut-points for MS to process data for time spent in moderate-to-vigorous physical activity, light physical activity, and sedentary behavior. Finally, patients completed the Short Physical Performance Battery (SPPB), the Six-Minute Walk Test, and the Timed 25-Foot Walk.

The median scores for time spent in moderate-to-vigorous physical activity and light physical activity were lower, and sedentary behavior was significantly greater, than those reported for older adults in the general population.

In addition, bivariate correlation analyses suggested that light physical activity and moderate to vigorous physical activity were associated with SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores, but the association was stronger for light physical activity. Regression analyses yielded significant associations between light physical activity, but not moderate-to-vigorous physical activity or sedentary behavior, and SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores.

NEW ORLEANS—Older adults with multiple sclerosis (MS) who engaged more in light physical activity demonstrated better physical function independent of sedentary behavior and moderate-to-vigorous activity, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Such results might underscore light physical activity as a suitable target of future rehabilitative interventions for improving physical function in older adults with MS,” said Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham.

Rate and pattern of participation in physical activity and sedentary behavior might be associated with a reduction of physical function among older adults with MS. Ms. Cederberg conducted a study that examined the associations among levels of light and moderate-to-vigorous physical activity, sedentary behavior, and physical function in older adults with MS.

Ms. Cederberg’s study sample included 40 older adults with MS with a median age of 60. Participants wore an accelerometer during the waking hours of a seven-day period. In addition, Ms. Cederberg used cut-points for MS to process data for time spent in moderate-to-vigorous physical activity, light physical activity, and sedentary behavior. Finally, patients completed the Short Physical Performance Battery (SPPB), the Six-Minute Walk Test, and the Timed 25-Foot Walk.

The median scores for time spent in moderate-to-vigorous physical activity and light physical activity were lower, and sedentary behavior was significantly greater, than those reported for older adults in the general population.

In addition, bivariate correlation analyses suggested that light physical activity and moderate to vigorous physical activity were associated with SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores, but the association was stronger for light physical activity. Regression analyses yielded significant associations between light physical activity, but not moderate-to-vigorous physical activity or sedentary behavior, and SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores.

NEW ORLEANS—Older adults with multiple sclerosis (MS) who engaged more in light physical activity demonstrated better physical function independent of sedentary behavior and moderate-to-vigorous activity, according to research presented at the 31st Annual Meeting of the Consortium of MS Centers.

“Such results might underscore light physical activity as a suitable target of future rehabilitative interventions for improving physical function in older adults with MS,” said Katie L.J. Cederberg, a doctoral student at the University of Alabama at Birmingham.

Rate and pattern of participation in physical activity and sedentary behavior might be associated with a reduction of physical function among older adults with MS. Ms. Cederberg conducted a study that examined the associations among levels of light and moderate-to-vigorous physical activity, sedentary behavior, and physical function in older adults with MS.

Ms. Cederberg’s study sample included 40 older adults with MS with a median age of 60. Participants wore an accelerometer during the waking hours of a seven-day period. In addition, Ms. Cederberg used cut-points for MS to process data for time spent in moderate-to-vigorous physical activity, light physical activity, and sedentary behavior. Finally, patients completed the Short Physical Performance Battery (SPPB), the Six-Minute Walk Test, and the Timed 25-Foot Walk.

The median scores for time spent in moderate-to-vigorous physical activity and light physical activity were lower, and sedentary behavior was significantly greater, than those reported for older adults in the general population.

In addition, bivariate correlation analyses suggested that light physical activity and moderate to vigorous physical activity were associated with SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores, but the association was stronger for light physical activity. Regression analyses yielded significant associations between light physical activity, but not moderate-to-vigorous physical activity or sedentary behavior, and SPPB, Six-Minute Walk Test, and Timed 25-Foot Walk scores.

NEW ORLEANS—Two-year analyses show that fewer patients required treatment with alemtuzumab than ocrelizumab to prevent one relapse, to prevent relapse in one patient, and to prevent six-month confirmed disability worsening in one patient versus subcutaneous interferon beta-1a, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers.

In the absence of head-to-head trials, researchers can use the number needed to treat to indirectly assess the comparative efficacy of disease-modifying therapies. Aaron L. Boster, MD, and colleagues analyzed the number needed to treat to prevent clinical disease events in studies of alemtuzumab and ocrelizumab in relapsing-remitting multiple sclerosis (MS). Dr. Boster is a clinical neuroimmunologist at the OhioHealth MS Clinic in Columbus.

Number needed to treat values were derived from post hoc analyses of two-year data from studies of alemtuzumab (12 mg) and ocrelizumab (600 mg). Alemtuzumab data were of pooled treatment-naive patients from the CAMMS223 and CARE-MS I studies (n = 786), and separately, patients with inadequate response to prior therapy from CARE-MS II (n = 628). Ocrelizumab data were derived from the OPERA I and II studies (n = 821 and n = 835, respectively). Alemtuzumab was administered as two annual courses; ocrelizumab was administered at baseline and weeks 24, 48, and 72. Number needed to treat was based on inverse of absolute risk differences versus subcutaneous interferon beta-1a 44 μg three times per week (common comparator) for annualized relapse rate and proportion of patients experiencing relapse, and the Altman method for six-month confirmed disability worsening. Lower number needed to treat values reflect greater efficacy.

Baseline mean Expanded Disability Status Scale (EDSS) scores were 2.0 for CAMMS223 and CARE-MS I, 2.7 for CARE-MS II, 2.9 for OPERA I, and 2.8 for OPERA II. Mean MS duration was 1.9 years in CAMMS223 and CARE-MS I, 4.5 years in CARE-MS II, and 6.7 years in OPERA I and II. Mean number of relapses in the previous two years was 2.5 for CAMMS223 and CARE-MS I, 2.8 for CARE-MS II, and 1.8 in OPERA I and II.

Alemtuzumab and ocrelizumab significantly reduced annualized relapse rates and confirmed disability worsening versus subcutaneous interferon beta-1a. Number needed to treat values to prevent one relapse versus subcutaneous interferon beta-1a were lower with alemtuzumab (CAMMS223/CARE-MS I: five; CARE-MS II: four) than with ocrelizumab (OPERA I/II: eight in each study), as were number needed to treat values to prevent one patient from experiencing relapse (CAMMS223/CARE-MS I and CARE-MS II: six in each study; OPERA I and II: eight in each study), and to prevent one patient from experiencing six-month confirmed disability worsening (CAMMS223/CARE-MS I: 15; CARE-MS II: 13; OPERA I: 23; OPERA II: 21).

Although the populations in the available datasets differ, these findings suggest a benefit of alemtuzumab over ocrelizumab.

This study was supported by Sanofi Genzyme.

NEW ORLEANS—Two-year analyses show that fewer patients required treatment with alemtuzumab than ocrelizumab to prevent one relapse, to prevent relapse in one patient, and to prevent six-month confirmed disability worsening in one patient versus subcutaneous interferon beta-1a, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers.

In the absence of head-to-head trials, researchers can use the number needed to treat to indirectly assess the comparative efficacy of disease-modifying therapies. Aaron L. Boster, MD, and colleagues analyzed the number needed to treat to prevent clinical disease events in studies of alemtuzumab and ocrelizumab in relapsing-remitting multiple sclerosis (MS). Dr. Boster is a clinical neuroimmunologist at the OhioHealth MS Clinic in Columbus.

Number needed to treat values were derived from post hoc analyses of two-year data from studies of alemtuzumab (12 mg) and ocrelizumab (600 mg). Alemtuzumab data were of pooled treatment-naive patients from the CAMMS223 and CARE-MS I studies (n = 786), and separately, patients with inadequate response to prior therapy from CARE-MS II (n = 628). Ocrelizumab data were derived from the OPERA I and II studies (n = 821 and n = 835, respectively). Alemtuzumab was administered as two annual courses; ocrelizumab was administered at baseline and weeks 24, 48, and 72. Number needed to treat was based on inverse of absolute risk differences versus subcutaneous interferon beta-1a 44 μg three times per week (common comparator) for annualized relapse rate and proportion of patients experiencing relapse, and the Altman method for six-month confirmed disability worsening. Lower number needed to treat values reflect greater efficacy.

Baseline mean Expanded Disability Status Scale (EDSS) scores were 2.0 for CAMMS223 and CARE-MS I, 2.7 for CARE-MS II, 2.9 for OPERA I, and 2.8 for OPERA II. Mean MS duration was 1.9 years in CAMMS223 and CARE-MS I, 4.5 years in CARE-MS II, and 6.7 years in OPERA I and II. Mean number of relapses in the previous two years was 2.5 for CAMMS223 and CARE-MS I, 2.8 for CARE-MS II, and 1.8 in OPERA I and II.

Alemtuzumab and ocrelizumab significantly reduced annualized relapse rates and confirmed disability worsening versus subcutaneous interferon beta-1a. Number needed to treat values to prevent one relapse versus subcutaneous interferon beta-1a were lower with alemtuzumab (CAMMS223/CARE-MS I: five; CARE-MS II: four) than with ocrelizumab (OPERA I/II: eight in each study), as were number needed to treat values to prevent one patient from experiencing relapse (CAMMS223/CARE-MS I and CARE-MS II: six in each study; OPERA I and II: eight in each study), and to prevent one patient from experiencing six-month confirmed disability worsening (CAMMS223/CARE-MS I: 15; CARE-MS II: 13; OPERA I: 23; OPERA II: 21).

Although the populations in the available datasets differ, these findings suggest a benefit of alemtuzumab over ocrelizumab.

This study was supported by Sanofi Genzyme.

NEW ORLEANS—Two-year analyses show that fewer patients required treatment with alemtuzumab than ocrelizumab to prevent one relapse, to prevent relapse in one patient, and to prevent six-month confirmed disability worsening in one patient versus subcutaneous interferon beta-1a, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers.

In the absence of head-to-head trials, researchers can use the number needed to treat to indirectly assess the comparative efficacy of disease-modifying therapies. Aaron L. Boster, MD, and colleagues analyzed the number needed to treat to prevent clinical disease events in studies of alemtuzumab and ocrelizumab in relapsing-remitting multiple sclerosis (MS). Dr. Boster is a clinical neuroimmunologist at the OhioHealth MS Clinic in Columbus.

Number needed to treat values were derived from post hoc analyses of two-year data from studies of alemtuzumab (12 mg) and ocrelizumab (600 mg). Alemtuzumab data were of pooled treatment-naive patients from the CAMMS223 and CARE-MS I studies (n = 786), and separately, patients with inadequate response to prior therapy from CARE-MS II (n = 628). Ocrelizumab data were derived from the OPERA I and II studies (n = 821 and n = 835, respectively). Alemtuzumab was administered as two annual courses; ocrelizumab was administered at baseline and weeks 24, 48, and 72. Number needed to treat was based on inverse of absolute risk differences versus subcutaneous interferon beta-1a 44 μg three times per week (common comparator) for annualized relapse rate and proportion of patients experiencing relapse, and the Altman method for six-month confirmed disability worsening. Lower number needed to treat values reflect greater efficacy.

Baseline mean Expanded Disability Status Scale (EDSS) scores were 2.0 for CAMMS223 and CARE-MS I, 2.7 for CARE-MS II, 2.9 for OPERA I, and 2.8 for OPERA II. Mean MS duration was 1.9 years in CAMMS223 and CARE-MS I, 4.5 years in CARE-MS II, and 6.7 years in OPERA I and II. Mean number of relapses in the previous two years was 2.5 for CAMMS223 and CARE-MS I, 2.8 for CARE-MS II, and 1.8 in OPERA I and II.

Alemtuzumab and ocrelizumab significantly reduced annualized relapse rates and confirmed disability worsening versus subcutaneous interferon beta-1a. Number needed to treat values to prevent one relapse versus subcutaneous interferon beta-1a were lower with alemtuzumab (CAMMS223/CARE-MS I: five; CARE-MS II: four) than with ocrelizumab (OPERA I/II: eight in each study), as were number needed to treat values to prevent one patient from experiencing relapse (CAMMS223/CARE-MS I and CARE-MS II: six in each study; OPERA I and II: eight in each study), and to prevent one patient from experiencing six-month confirmed disability worsening (CAMMS223/CARE-MS I: 15; CARE-MS II: 13; OPERA I: 23; OPERA II: 21).

Although the populations in the available datasets differ, these findings suggest a benefit of alemtuzumab over ocrelizumab.

This study was supported by Sanofi Genzyme.

A Large Case–Control Analysis

Previous studies have provided evidence for an MS prodrome that occurs years before a demyelinating event or the onset of clinical symptoms. Many of these studies, however, have been limited by a retrospective design or by the absence of a control group.

To analyze the question further, Dr. Tremlett and colleagues examined data from linked health administrative and clinical databases in the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia, which were chosen for their geographic diversity and comprehensive data. The researchers created a health administrative cohort, which was based on administrative data, and an MS clinic-derived cohort, which used administrative and clinical data. The study’s primary outcome was all-cause use of health care during each of the five years before the health administrative index date (ie, the first demyelinating disease-related claim) or clinical index date (ie, the date of MS symptom onset).

Health Care Use Increased in Prodromal MS

The health administrative cohort included 14,428 people with MS and 72,059 matched controls. In all, 10,525 (73%) of the patients with MS were women, and their mean age at the health administrative index date was 43. Compared with controls, annual health care use increased steadily between five years and one year before the first demyelinating disease claim in these patients.

The mean number of hospital admissions was 26% higher in people with MS than in controls in the fifth year before the index date, and 78% higher in the year before the index date. The mean number of physician claims was 24% higher in people with MS than in controls in the fifth year before the index date, and 88% higher in people with MS than in controls in the year before the index date. Also, the mean number of prescribed drug classes was 23% higher in people with MS than in matched controls in the fifth year before the index date, and 49% higher in people with MS than in controls in the year before the index date.

The MS clinic cohort included 3,202 people with MS and 16,006 matched controls. In all, 2,368 (74%) of people with MS were women, and the mean age at the clinical index date was approximately 37. Compared with the health administrative cohort, this cohort had similar patterns for physician claims and prescriptions, although the differences in use in each of the five years mostly did not reach statistical significance.

“To gain a better insight into the MS prodrome, the complex reasons for increased health care use will need to be established, for example, through access of additional administrative data such as the specific diagnostic codes related to a hospital admission or physician visit, or the therapeutic drug class for a prescription,” Dr. Tremlett concluded.

—Erik Greb

Suggested Reading

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017 Apr 20 [Epub ahead of print].

A Large Case–Control Analysis

Previous studies have provided evidence for an MS prodrome that occurs years before a demyelinating event or the onset of clinical symptoms. Many of these studies, however, have been limited by a retrospective design or by the absence of a control group.

To analyze the question further, Dr. Tremlett and colleagues examined data from linked health administrative and clinical databases in the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia, which were chosen for their geographic diversity and comprehensive data. The researchers created a health administrative cohort, which was based on administrative data, and an MS clinic-derived cohort, which used administrative and clinical data. The study’s primary outcome was all-cause use of health care during each of the five years before the health administrative index date (ie, the first demyelinating disease-related claim) or clinical index date (ie, the date of MS symptom onset).

Health Care Use Increased in Prodromal MS

The health administrative cohort included 14,428 people with MS and 72,059 matched controls. In all, 10,525 (73%) of the patients with MS were women, and their mean age at the health administrative index date was 43. Compared with controls, annual health care use increased steadily between five years and one year before the first demyelinating disease claim in these patients.

The mean number of hospital admissions was 26% higher in people with MS than in controls in the fifth year before the index date, and 78% higher in the year before the index date. The mean number of physician claims was 24% higher in people with MS than in controls in the fifth year before the index date, and 88% higher in people with MS than in controls in the year before the index date. Also, the mean number of prescribed drug classes was 23% higher in people with MS than in matched controls in the fifth year before the index date, and 49% higher in people with MS than in controls in the year before the index date.

The MS clinic cohort included 3,202 people with MS and 16,006 matched controls. In all, 2,368 (74%) of people with MS were women, and the mean age at the clinical index date was approximately 37. Compared with the health administrative cohort, this cohort had similar patterns for physician claims and prescriptions, although the differences in use in each of the five years mostly did not reach statistical significance.

“To gain a better insight into the MS prodrome, the complex reasons for increased health care use will need to be established, for example, through access of additional administrative data such as the specific diagnostic codes related to a hospital admission or physician visit, or the therapeutic drug class for a prescription,” Dr. Tremlett concluded.

—Erik Greb

Suggested Reading

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017 Apr 20 [Epub ahead of print].

A Large Case–Control Analysis

Previous studies have provided evidence for an MS prodrome that occurs years before a demyelinating event or the onset of clinical symptoms. Many of these studies, however, have been limited by a retrospective design or by the absence of a control group.

To analyze the question further, Dr. Tremlett and colleagues examined data from linked health administrative and clinical databases in the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia, which were chosen for their geographic diversity and comprehensive data. The researchers created a health administrative cohort, which was based on administrative data, and an MS clinic-derived cohort, which used administrative and clinical data. The study’s primary outcome was all-cause use of health care during each of the five years before the health administrative index date (ie, the first demyelinating disease-related claim) or clinical index date (ie, the date of MS symptom onset).

Health Care Use Increased in Prodromal MS

The health administrative cohort included 14,428 people with MS and 72,059 matched controls. In all, 10,525 (73%) of the patients with MS were women, and their mean age at the health administrative index date was 43. Compared with controls, annual health care use increased steadily between five years and one year before the first demyelinating disease claim in these patients.

The mean number of hospital admissions was 26% higher in people with MS than in controls in the fifth year before the index date, and 78% higher in the year before the index date. The mean number of physician claims was 24% higher in people with MS than in controls in the fifth year before the index date, and 88% higher in people with MS than in controls in the year before the index date. Also, the mean number of prescribed drug classes was 23% higher in people with MS than in matched controls in the fifth year before the index date, and 49% higher in people with MS than in controls in the year before the index date.

The MS clinic cohort included 3,202 people with MS and 16,006 matched controls. In all, 2,368 (74%) of people with MS were women, and the mean age at the clinical index date was approximately 37. Compared with the health administrative cohort, this cohort had similar patterns for physician claims and prescriptions, although the differences in use in each of the five years mostly did not reach statistical significance.

“To gain a better insight into the MS prodrome, the complex reasons for increased health care use will need to be established, for example, through access of additional administrative data such as the specific diagnostic codes related to a hospital admission or physician visit, or the therapeutic drug class for a prescription,” Dr. Tremlett concluded.

—Erik Greb

Suggested Reading

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017 Apr 20 [Epub ahead of print].

NEW ORLEANS—Analysis of pooled data from the CLARITY and ONWARD studies showed that cladribine tablets 3.5 mg/kg decreased annualized relapse rate by 57% and reduced the risk for six-month confirmed disability progression by 39% versus placebo in a population of patients with active relapsing multiple sclerosis (MS). These findings were presented at the 31st Annual Meeting of the Consortium of MS Centers.

Treatment with cladribine tablets in the CLARITY and ONWARD studies demonstrated efficacy versus placebo across a range of patients with active MS. “Combining efficacy data from the double-blind periods of these studies allows assessment of the efficacy of two years’ treatment with cladribine tablets 3.5 mg/kg,” said Gavin Giovannoni, MBBCh, PhD, on behalf of his research colleagues. Dr. Giovannoni is a Professor at the Blizard Institute at Barts and the London School of Medicine and Dentistry in London.

Dr. Giovannoni and colleagues used pooled data from the two-year, double-blind periods of CLARITY and ONWARD to analyze the efficacy of cladribine tablets 3.5 mg/kg in patients with relapsing MS (n = 1,067) and in subgroups defined by baseline characteristics. Patients from ONWARD on cladribine tablets or placebo were also taking interferon beta. Annualized relapse rates and three-month and six-month confirmed disability progression were compared using relative risk ratios from a Poisson regression model, hazard ratios from a Cox proportional hazard model, and 95% confidence intervals for patients treated with cladribine tablets 3.5 mg/kg or placebo. The subgroups analyzed included, among others, patients with no T1 gadolinium-enhancing lesions (n = 759) or one or more T1 gadolinium-enhancing lesions (n = 308) and patients with an Expanded Disability Status Scale (EDSS) score of 3.0 or lower (n = 653) or 3.5 or greater (n = 414).

For annualized relapse rate, consistent benefits were seen with cladribine tablets 3.5 mg/kg versus placebo in the overall population (relative risk ratio: 0.43) and in the subgroups: no T1 gadolinium-enhancing lesions, 0.46; one or more T1 gadolinium-enhancing lesions, 0.38; EDSS of 3.0 or lower, 0.40; EDSS of 3.5 or greater, 0.47. Benefits favored cladribine tablets 3.5 mg/kg versus placebo in the overall population for time to three-month confirmed disability progression (hazard ratio: 0.64) and six-month confirmed disability progression (hazard ratio: 0.61) and in each of these outcomes in a majority of subgroups. For three-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.75; EDSS of 3.0 or lower, hazard ratio: 0.76; EDSS of 3.5 or greater, hazard ratio: 0.55. For six-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.66; EDSS of 3.0 or lower, hazard ratio: 0.75; EDSS of 3.5 or greater, hazard ratio: 0.51.

This study was supported by EMD Serono.

NEW ORLEANS—Analysis of pooled data from the CLARITY and ONWARD studies showed that cladribine tablets 3.5 mg/kg decreased annualized relapse rate by 57% and reduced the risk for six-month confirmed disability progression by 39% versus placebo in a population of patients with active relapsing multiple sclerosis (MS). These findings were presented at the 31st Annual Meeting of the Consortium of MS Centers.

Treatment with cladribine tablets in the CLARITY and ONWARD studies demonstrated efficacy versus placebo across a range of patients with active MS. “Combining efficacy data from the double-blind periods of these studies allows assessment of the efficacy of two years’ treatment with cladribine tablets 3.5 mg/kg,” said Gavin Giovannoni, MBBCh, PhD, on behalf of his research colleagues. Dr. Giovannoni is a Professor at the Blizard Institute at Barts and the London School of Medicine and Dentistry in London.

Dr. Giovannoni and colleagues used pooled data from the two-year, double-blind periods of CLARITY and ONWARD to analyze the efficacy of cladribine tablets 3.5 mg/kg in patients with relapsing MS (n = 1,067) and in subgroups defined by baseline characteristics. Patients from ONWARD on cladribine tablets or placebo were also taking interferon beta. Annualized relapse rates and three-month and six-month confirmed disability progression were compared using relative risk ratios from a Poisson regression model, hazard ratios from a Cox proportional hazard model, and 95% confidence intervals for patients treated with cladribine tablets 3.5 mg/kg or placebo. The subgroups analyzed included, among others, patients with no T1 gadolinium-enhancing lesions (n = 759) or one or more T1 gadolinium-enhancing lesions (n = 308) and patients with an Expanded Disability Status Scale (EDSS) score of 3.0 or lower (n = 653) or 3.5 or greater (n = 414).

For annualized relapse rate, consistent benefits were seen with cladribine tablets 3.5 mg/kg versus placebo in the overall population (relative risk ratio: 0.43) and in the subgroups: no T1 gadolinium-enhancing lesions, 0.46; one or more T1 gadolinium-enhancing lesions, 0.38; EDSS of 3.0 or lower, 0.40; EDSS of 3.5 or greater, 0.47. Benefits favored cladribine tablets 3.5 mg/kg versus placebo in the overall population for time to three-month confirmed disability progression (hazard ratio: 0.64) and six-month confirmed disability progression (hazard ratio: 0.61) and in each of these outcomes in a majority of subgroups. For three-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.75; EDSS of 3.0 or lower, hazard ratio: 0.76; EDSS of 3.5 or greater, hazard ratio: 0.55. For six-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.66; EDSS of 3.0 or lower, hazard ratio: 0.75; EDSS of 3.5 or greater, hazard ratio: 0.51.

This study was supported by EMD Serono.

NEW ORLEANS—Analysis of pooled data from the CLARITY and ONWARD studies showed that cladribine tablets 3.5 mg/kg decreased annualized relapse rate by 57% and reduced the risk for six-month confirmed disability progression by 39% versus placebo in a population of patients with active relapsing multiple sclerosis (MS). These findings were presented at the 31st Annual Meeting of the Consortium of MS Centers.

Treatment with cladribine tablets in the CLARITY and ONWARD studies demonstrated efficacy versus placebo across a range of patients with active MS. “Combining efficacy data from the double-blind periods of these studies allows assessment of the efficacy of two years’ treatment with cladribine tablets 3.5 mg/kg,” said Gavin Giovannoni, MBBCh, PhD, on behalf of his research colleagues. Dr. Giovannoni is a Professor at the Blizard Institute at Barts and the London School of Medicine and Dentistry in London.

Dr. Giovannoni and colleagues used pooled data from the two-year, double-blind periods of CLARITY and ONWARD to analyze the efficacy of cladribine tablets 3.5 mg/kg in patients with relapsing MS (n = 1,067) and in subgroups defined by baseline characteristics. Patients from ONWARD on cladribine tablets or placebo were also taking interferon beta. Annualized relapse rates and three-month and six-month confirmed disability progression were compared using relative risk ratios from a Poisson regression model, hazard ratios from a Cox proportional hazard model, and 95% confidence intervals for patients treated with cladribine tablets 3.5 mg/kg or placebo. The subgroups analyzed included, among others, patients with no T1 gadolinium-enhancing lesions (n = 759) or one or more T1 gadolinium-enhancing lesions (n = 308) and patients with an Expanded Disability Status Scale (EDSS) score of 3.0 or lower (n = 653) or 3.5 or greater (n = 414).

For annualized relapse rate, consistent benefits were seen with cladribine tablets 3.5 mg/kg versus placebo in the overall population (relative risk ratio: 0.43) and in the subgroups: no T1 gadolinium-enhancing lesions, 0.46; one or more T1 gadolinium-enhancing lesions, 0.38; EDSS of 3.0 or lower, 0.40; EDSS of 3.5 or greater, 0.47. Benefits favored cladribine tablets 3.5 mg/kg versus placebo in the overall population for time to three-month confirmed disability progression (hazard ratio: 0.64) and six-month confirmed disability progression (hazard ratio: 0.61) and in each of these outcomes in a majority of subgroups. For three-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.75; EDSS of 3.0 or lower, hazard ratio: 0.76; EDSS of 3.5 or greater, hazard ratio: 0.55. For six-month confirmed disability progression: no T1 gadolinium-enhancing lesions, hazard ratio: 0.59; one or more T1 gadolinium-enhancing lesions, hazard ratio: 0.66; EDSS of 3.0 or lower, hazard ratio: 0.75; EDSS of 3.5 or greater, hazard ratio: 0.51.

This study was supported by EMD Serono.

NEW ORLEANS—Ublituximab, a novel glycoengineered anti-CD20 antibody, is well tolerated and demonstrates rapid and robust B-cell depletion, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Unlike other anti-CD20s, ublituximab can be delivered in shorter infusions, providing a convenience benefit for patients,” reported Amy Lovett-Racke, PhD, and her research colleagues. Dr. Lovett-Racke is a Professor in the Department of Microbial Infection and Immunity at Ohio State University Medical Center in Columbus.

Patients with relapsing or primary progressive forms of multiple sclerosis (MS) have shown significant clinical improvement after B-cell depletion with an anti-CD20 antibody. Ublituximab is a chimeric monoclonal antibody that targets a unique epitope on the CD20 antigen. It has been glycoengineered to enhance affinity for all variants of FcgRIIIa receptors, demonstrating greater antibody-dependent cellular cytotoxicity (ADCC) activity than rituximab. Ublituximab is currently in phase III trials for the treatment of hematologic malignancies.

To determine the level of B-cell depletion by ublituximab in subjects with relapsing MS, Dr. Lovett-Racke and colleagues conducted a 52-week, phase II, placebo-controlled, multicenter study that was designed to assess the infusion time and optimal dose as well as the safety and tolerability of ublituximab in patients with relapsing MS. The investigators also performed radiologic and clinical analyses. Optimal dosing was determined by B-cell depletion, defined as percentage of CD19+ B cells present following ublituximab administration. This percentage was calculated by gating the entire lymphocyte/myeloid population. Within this population, CD19+ CD3− cells were gated, and the percentage of CD19+ B cells was determined.

To date, B-cell data from 11 subjects have been analyzed up to week four of the 52-week study, encompassing two infusions of ublituximab. No severe adverse events have been reported, including in subjects receiving rapid infusions. Only patients whose B-cell levels were within a normal range (≥ 5% of total lymphocytes) at screening were included in the study. At week four (one week post second infusion), median B-cell depletion was 99% from baseline in ublituximab-treated subjects, while controls maintained similar B-cell levels, as compared with baseline.

This study was supported by TG Therapeutics.

NEW ORLEANS—Ublituximab, a novel glycoengineered anti-CD20 antibody, is well tolerated and demonstrates rapid and robust B-cell depletion, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Unlike other anti-CD20s, ublituximab can be delivered in shorter infusions, providing a convenience benefit for patients,” reported Amy Lovett-Racke, PhD, and her research colleagues. Dr. Lovett-Racke is a Professor in the Department of Microbial Infection and Immunity at Ohio State University Medical Center in Columbus.

Patients with relapsing or primary progressive forms of multiple sclerosis (MS) have shown significant clinical improvement after B-cell depletion with an anti-CD20 antibody. Ublituximab is a chimeric monoclonal antibody that targets a unique epitope on the CD20 antigen. It has been glycoengineered to enhance affinity for all variants of FcgRIIIa receptors, demonstrating greater antibody-dependent cellular cytotoxicity (ADCC) activity than rituximab. Ublituximab is currently in phase III trials for the treatment of hematologic malignancies.

To determine the level of B-cell depletion by ublituximab in subjects with relapsing MS, Dr. Lovett-Racke and colleagues conducted a 52-week, phase II, placebo-controlled, multicenter study that was designed to assess the infusion time and optimal dose as well as the safety and tolerability of ublituximab in patients with relapsing MS. The investigators also performed radiologic and clinical analyses. Optimal dosing was determined by B-cell depletion, defined as percentage of CD19+ B cells present following ublituximab administration. This percentage was calculated by gating the entire lymphocyte/myeloid population. Within this population, CD19+ CD3− cells were gated, and the percentage of CD19+ B cells was determined.

To date, B-cell data from 11 subjects have been analyzed up to week four of the 52-week study, encompassing two infusions of ublituximab. No severe adverse events have been reported, including in subjects receiving rapid infusions. Only patients whose B-cell levels were within a normal range (≥ 5% of total lymphocytes) at screening were included in the study. At week four (one week post second infusion), median B-cell depletion was 99% from baseline in ublituximab-treated subjects, while controls maintained similar B-cell levels, as compared with baseline.

This study was supported by TG Therapeutics.

NEW ORLEANS—Ublituximab, a novel glycoengineered anti-CD20 antibody, is well tolerated and demonstrates rapid and robust B-cell depletion, according to a report presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis Centers. “Unlike other anti-CD20s, ublituximab can be delivered in shorter infusions, providing a convenience benefit for patients,” reported Amy Lovett-Racke, PhD, and her research colleagues. Dr. Lovett-Racke is a Professor in the Department of Microbial Infection and Immunity at Ohio State University Medical Center in Columbus.

Patients with relapsing or primary progressive forms of multiple sclerosis (MS) have shown significant clinical improvement after B-cell depletion with an anti-CD20 antibody. Ublituximab is a chimeric monoclonal antibody that targets a unique epitope on the CD20 antigen. It has been glycoengineered to enhance affinity for all variants of FcgRIIIa receptors, demonstrating greater antibody-dependent cellular cytotoxicity (ADCC) activity than rituximab. Ublituximab is currently in phase III trials for the treatment of hematologic malignancies.

To determine the level of B-cell depletion by ublituximab in subjects with relapsing MS, Dr. Lovett-Racke and colleagues conducted a 52-week, phase II, placebo-controlled, multicenter study that was designed to assess the infusion time and optimal dose as well as the safety and tolerability of ublituximab in patients with relapsing MS. The investigators also performed radiologic and clinical analyses. Optimal dosing was determined by B-cell depletion, defined as percentage of CD19+ B cells present following ublituximab administration. This percentage was calculated by gating the entire lymphocyte/myeloid population. Within this population, CD19+ CD3− cells were gated, and the percentage of CD19+ B cells was determined.

To date, B-cell data from 11 subjects have been analyzed up to week four of the 52-week study, encompassing two infusions of ublituximab. No severe adverse events have been reported, including in subjects receiving rapid infusions. Only patients whose B-cell levels were within a normal range (≥ 5% of total lymphocytes) at screening were included in the study. At week four (one week post second infusion), median B-cell depletion was 99% from baseline in ublituximab-treated subjects, while controls maintained similar B-cell levels, as compared with baseline.

This study was supported by TG Therapeutics.

NEW ORLEANS—MRI lesion activity and relapses in the phase III TRANSFORMS study predicted relapses in the short and long terms among patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. In addition, baseline Expanded Disability Status Scale (EDSS) score, age, and disease duration predicted six-month confirmed disability progression.

Disease and treatment history, early MRI lesion activity, and relapses may predict long-term clinical outcomes in patients with relapsing forms of MS. To test the ability of parameters at baseline and during treatment to predict relapses or six-month disability progression in the short and long terms, Dr. Boster and colleagues conducted a post-hoc analysis of the 36-month follow-up of TRANSFORMS, a 12-month, double-blind study in which researchers randomized patients to oral fingolimod or intramuscular interferon beta-1a.

After the 12-month, double-blind study, patients could enter a long-term extension. Upon entering the extension, researchers switched patients who originally received intramuscular interferon beta-1a to fingolimod. The investigators used unadjusted logistic regression to assess which parameters from baseline to month 12 predicted clinical outcomes (ie, relapses or six-month confirmed disability progress, measured using the EDSS) during months 12–24 and months 12–48.

In all, researchers randomized 1,292 patients in TRANSFORMS. Predictors of relapses in the short and long terms included a combination of MRI lesion activity (ie, at least one gadolinium-enhancing lesion or at least two new T2 lesions) and at least one confirmed relapse (odds ratio [OR], 2.776 for months 12–24; OR, 3.703 for months 12–48). The number of confirmed relapses from baseline to month 12 also predicted relapses during the extension.

Novartis Pharmaceuticals supported this study.

NEW ORLEANS—MRI lesion activity and relapses in the phase III TRANSFORMS study predicted relapses in the short and long terms among patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. In addition, baseline Expanded Disability Status Scale (EDSS) score, age, and disease duration predicted six-month confirmed disability progression.

Disease and treatment history, early MRI lesion activity, and relapses may predict long-term clinical outcomes in patients with relapsing forms of MS. To test the ability of parameters at baseline and during treatment to predict relapses or six-month disability progression in the short and long terms, Dr. Boster and colleagues conducted a post-hoc analysis of the 36-month follow-up of TRANSFORMS, a 12-month, double-blind study in which researchers randomized patients to oral fingolimod or intramuscular interferon beta-1a.

After the 12-month, double-blind study, patients could enter a long-term extension. Upon entering the extension, researchers switched patients who originally received intramuscular interferon beta-1a to fingolimod. The investigators used unadjusted logistic regression to assess which parameters from baseline to month 12 predicted clinical outcomes (ie, relapses or six-month confirmed disability progress, measured using the EDSS) during months 12–24 and months 12–48.

In all, researchers randomized 1,292 patients in TRANSFORMS. Predictors of relapses in the short and long terms included a combination of MRI lesion activity (ie, at least one gadolinium-enhancing lesion or at least two new T2 lesions) and at least one confirmed relapse (odds ratio [OR], 2.776 for months 12–24; OR, 3.703 for months 12–48). The number of confirmed relapses from baseline to month 12 also predicted relapses during the extension.

Novartis Pharmaceuticals supported this study.

NEW ORLEANS—MRI lesion activity and relapses in the phase III TRANSFORMS study predicted relapses in the short and long terms among patients with multiple sclerosis (MS), according to research presented at the 31st Annual Meeting of the Consortium of MS Centers. In addition, baseline Expanded Disability Status Scale (EDSS) score, age, and disease duration predicted six-month confirmed disability progression.

Disease and treatment history, early MRI lesion activity, and relapses may predict long-term clinical outcomes in patients with relapsing forms of MS. To test the ability of parameters at baseline and during treatment to predict relapses or six-month disability progression in the short and long terms, Dr. Boster and colleagues conducted a post-hoc analysis of the 36-month follow-up of TRANSFORMS, a 12-month, double-blind study in which researchers randomized patients to oral fingolimod or intramuscular interferon beta-1a.

After the 12-month, double-blind study, patients could enter a long-term extension. Upon entering the extension, researchers switched patients who originally received intramuscular interferon beta-1a to fingolimod. The investigators used unadjusted logistic regression to assess which parameters from baseline to month 12 predicted clinical outcomes (ie, relapses or six-month confirmed disability progress, measured using the EDSS) during months 12–24 and months 12–48.

In all, researchers randomized 1,292 patients in TRANSFORMS. Predictors of relapses in the short and long terms included a combination of MRI lesion activity (ie, at least one gadolinium-enhancing lesion or at least two new T2 lesions) and at least one confirmed relapse (odds ratio [OR], 2.776 for months 12–24; OR, 3.703 for months 12–48). The number of confirmed relapses from baseline to month 12 also predicted relapses during the extension.

Novartis Pharmaceuticals supported this study.

BOSTON – Prior Epstein-Barr virus (EBV) infection and prior herpes simplex virus (HSV) infection each appear to be associated with development of pediatric-onset multiple sclerosis (MS), according to findings from a large national case-control study.

Samples from 360 children with MS or clinically isolated syndrome and 496 frequency-matched controls recruited from 16 pediatric MS centers across the United States were tested for EBV, cytomegalovirus (CMV), and HSV antibodies and for 25-(OH)-vitamin D levels. After adjusting for age, sex, and race/ethnicity, evidence of a remote infection with EBV was strongly associated with higher risk of pediatric-onset MS (odds ratio, 3.6), Bardia Nourbakhsh, MD, reported at the annual meeting of the American Academy of Neurology.

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[email protected]

BOSTON – Prior Epstein-Barr virus (EBV) infection and prior herpes simplex virus (HSV) infection each appear to be associated with development of pediatric-onset multiple sclerosis (MS), according to findings from a large national case-control study.

Samples from 360 children with MS or clinically isolated syndrome and 496 frequency-matched controls recruited from 16 pediatric MS centers across the United States were tested for EBV, cytomegalovirus (CMV), and HSV antibodies and for 25-(OH)-vitamin D levels. After adjusting for age, sex, and race/ethnicity, evidence of a remote infection with EBV was strongly associated with higher risk of pediatric-onset MS (odds ratio, 3.6), Bardia Nourbakhsh, MD, reported at the annual meeting of the American Academy of Neurology.

copyright Zerbor/Thinkstock

[email protected]

BOSTON – Prior Epstein-Barr virus (EBV) infection and prior herpes simplex virus (HSV) infection each appear to be associated with development of pediatric-onset multiple sclerosis (MS), according to findings from a large national case-control study.

Samples from 360 children with MS or clinically isolated syndrome and 496 frequency-matched controls recruited from 16 pediatric MS centers across the United States were tested for EBV, cytomegalovirus (CMV), and HSV antibodies and for 25-(OH)-vitamin D levels. After adjusting for age, sex, and race/ethnicity, evidence of a remote infection with EBV was strongly associated with higher risk of pediatric-onset MS (odds ratio, 3.6), Bardia Nourbakhsh, MD, reported at the annual meeting of the American Academy of Neurology.

copyright Zerbor/Thinkstock

[email protected]

BOSTON—Misdiagnosing optic neuritis may expose patients to risks associated with undergoing MRI with a contrast agent, lumbar puncture, and high-dose steroid treatment. It also costs patients and hospitals time and money. Leanne Stunkel, MD, a neurology resident at Washington University in St. Louis, and her colleagues observed a 60% misdiagnosis rate of optic neuritis among patients who were referred to their neuro-ophthalmology clinic, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology.

“The most common [diagnostic] errors were overreliance on a single item of history and failure to consider alternative diagnoses,” said Dr. Stunkel.

Optic neuritis is an acute inflammatory demyelinating condition of the optic nerve. Presenting symptoms include acute or subacute vision loss, pain with eye movement, and changes in color vision, especially affecting the color red, said Dr. Stunkel. Many patients who were referred to their tertiary care clinic for optic neuritis turned out to have other conditions, which prompted the researchers to find out more about optic neuritis misdiagnosis.

Previous studies found a misdiagnosis rate of between 10% and 40%, but none of these studies examined which errors led to these misdiagnoses. To determine how often optic neuritis is misdiagnosed and which diagnostic errors play a role, and to identify diagnoses commonly mistaken for optic neuritis, Dr. Stunkel and colleagues performed a retrospective chart review.

The researchers reviewed new patient encounters between January 2014 and October 2016 to identify patients referred with a diagnosis of optic neuritis. Experienced neuro-ophthalmologists determined the final diagnosis. The researchers then applied the Diagnosis Error Evaluation and Research (DEER) taxonomy tool to identify diagnostic errors in cases in which the patient did not have optic neuritis.

A total of 122 patients were referred for optic neuritis during the study period. Only 40% of these patients were diagnosed with optic neuritis, and 60% of patients had alternative diagnoses. The most common alternative diagnoses were headache with eye pain and visual symptoms (22%), functional visual loss (19%), and other optic neuropathies (16%).

In addition, 15% of patients had retinal or macular problems rather than pathology of the optic nerve. Other diagnoses included neoplasms, congenital disk abnormalities, and inflammatory conditions that affected other parts of the eye.

The most common diagnostic errors were from problems eliciting or interpreting the history (33%). “We saw an overreliance on history of risk factors such as multiple sclerosis or other inflammatory disorders and some failure to elicit the fact that these were brief stereotyped episodes of vision loss, like in a migraine aura,” said Dr. Stunkel.

Twenty-one percent of diagnostic errors were due to errors interpreting physical exam findings, and 14% of errors were due to misinterpretation of diagnostic tests. Finally, 32% of diagnostic errors resulted from failure to consider alternative diagnoses. Of patients who did not have optic neuritis, 17% had already received a lumbar puncture, 17% had received a contrast MRI that turned out to be negative, and 11 patients had inappropriately received IV steroids, said Dr. Stunkel.

Some of the study limitations include that the DEER category assignments were subjective, and that not every referral for optic neuritis was included in the study due to limitations of the clinic’s electronic medical records system, said Dr. Stunkel.

—Erica Tricarico

BOSTON—Misdiagnosing optic neuritis may expose patients to risks associated with undergoing MRI with a contrast agent, lumbar puncture, and high-dose steroid treatment. It also costs patients and hospitals time and money. Leanne Stunkel, MD, a neurology resident at Washington University in St. Louis, and her colleagues observed a 60% misdiagnosis rate of optic neuritis among patients who were referred to their neuro-ophthalmology clinic, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology.

“The most common [diagnostic] errors were overreliance on a single item of history and failure to consider alternative diagnoses,” said Dr. Stunkel.

Optic neuritis is an acute inflammatory demyelinating condition of the optic nerve. Presenting symptoms include acute or subacute vision loss, pain with eye movement, and changes in color vision, especially affecting the color red, said Dr. Stunkel. Many patients who were referred to their tertiary care clinic for optic neuritis turned out to have other conditions, which prompted the researchers to find out more about optic neuritis misdiagnosis.

Previous studies found a misdiagnosis rate of between 10% and 40%, but none of these studies examined which errors led to these misdiagnoses. To determine how often optic neuritis is misdiagnosed and which diagnostic errors play a role, and to identify diagnoses commonly mistaken for optic neuritis, Dr. Stunkel and colleagues performed a retrospective chart review.

The researchers reviewed new patient encounters between January 2014 and October 2016 to identify patients referred with a diagnosis of optic neuritis. Experienced neuro-ophthalmologists determined the final diagnosis. The researchers then applied the Diagnosis Error Evaluation and Research (DEER) taxonomy tool to identify diagnostic errors in cases in which the patient did not have optic neuritis.

A total of 122 patients were referred for optic neuritis during the study period. Only 40% of these patients were diagnosed with optic neuritis, and 60% of patients had alternative diagnoses. The most common alternative diagnoses were headache with eye pain and visual symptoms (22%), functional visual loss (19%), and other optic neuropathies (16%).

In addition, 15% of patients had retinal or macular problems rather than pathology of the optic nerve. Other diagnoses included neoplasms, congenital disk abnormalities, and inflammatory conditions that affected other parts of the eye.

The most common diagnostic errors were from problems eliciting or interpreting the history (33%). “We saw an overreliance on history of risk factors such as multiple sclerosis or other inflammatory disorders and some failure to elicit the fact that these were brief stereotyped episodes of vision loss, like in a migraine aura,” said Dr. Stunkel.

Twenty-one percent of diagnostic errors were due to errors interpreting physical exam findings, and 14% of errors were due to misinterpretation of diagnostic tests. Finally, 32% of diagnostic errors resulted from failure to consider alternative diagnoses. Of patients who did not have optic neuritis, 17% had already received a lumbar puncture, 17% had received a contrast MRI that turned out to be negative, and 11 patients had inappropriately received IV steroids, said Dr. Stunkel.

Some of the study limitations include that the DEER category assignments were subjective, and that not every referral for optic neuritis was included in the study due to limitations of the clinic’s electronic medical records system, said Dr. Stunkel.

—Erica Tricarico

BOSTON—Misdiagnosing optic neuritis may expose patients to risks associated with undergoing MRI with a contrast agent, lumbar puncture, and high-dose steroid treatment. It also costs patients and hospitals time and money. Leanne Stunkel, MD, a neurology resident at Washington University in St. Louis, and her colleagues observed a 60% misdiagnosis rate of optic neuritis among patients who were referred to their neuro-ophthalmology clinic, according to a study presented at the 69th Annual Meeting of the American Academy of Neurology.

“The most common [diagnostic] errors were overreliance on a single item of history and failure to consider alternative diagnoses,” said Dr. Stunkel.

Optic neuritis is an acute inflammatory demyelinating condition of the optic nerve. Presenting symptoms include acute or subacute vision loss, pain with eye movement, and changes in color vision, especially affecting the color red, said Dr. Stunkel. Many patients who were referred to their tertiary care clinic for optic neuritis turned out to have other conditions, which prompted the researchers to find out more about optic neuritis misdiagnosis.

Previous studies found a misdiagnosis rate of between 10% and 40%, but none of these studies examined which errors led to these misdiagnoses. To determine how often optic neuritis is misdiagnosed and which diagnostic errors play a role, and to identify diagnoses commonly mistaken for optic neuritis, Dr. Stunkel and colleagues performed a retrospective chart review.

The researchers reviewed new patient encounters between January 2014 and October 2016 to identify patients referred with a diagnosis of optic neuritis. Experienced neuro-ophthalmologists determined the final diagnosis. The researchers then applied the Diagnosis Error Evaluation and Research (DEER) taxonomy tool to identify diagnostic errors in cases in which the patient did not have optic neuritis.

A total of 122 patients were referred for optic neuritis during the study period. Only 40% of these patients were diagnosed with optic neuritis, and 60% of patients had alternative diagnoses. The most common alternative diagnoses were headache with eye pain and visual symptoms (22%), functional visual loss (19%), and other optic neuropathies (16%).

In addition, 15% of patients had retinal or macular problems rather than pathology of the optic nerve. Other diagnoses included neoplasms, congenital disk abnormalities, and inflammatory conditions that affected other parts of the eye.

The most common diagnostic errors were from problems eliciting or interpreting the history (33%). “We saw an overreliance on history of risk factors such as multiple sclerosis or other inflammatory disorders and some failure to elicit the fact that these were brief stereotyped episodes of vision loss, like in a migraine aura,” said Dr. Stunkel.

Twenty-one percent of diagnostic errors were due to errors interpreting physical exam findings, and 14% of errors were due to misinterpretation of diagnostic tests. Finally, 32% of diagnostic errors resulted from failure to consider alternative diagnoses. Of patients who did not have optic neuritis, 17% had already received a lumbar puncture, 17% had received a contrast MRI that turned out to be negative, and 11 patients had inappropriately received IV steroids, said Dr. Stunkel.

Some of the study limitations include that the DEER category assignments were subjective, and that not every referral for optic neuritis was included in the study due to limitations of the clinic’s electronic medical records system, said Dr. Stunkel.

—Erica Tricarico

A variant in the TNFSF13B gene has been linked to susceptibility to both multiple sclerosis and systemic lupus erythematosus, according to a report published online April 26 in the New England Journal of Medicine.

This gene encodes the cytokine B-cell activating factor (BAFF), which is essential for B-cell activation, differentiation, and survival. BAFF is targeted by agents such as belimumab that are used in the treatment of autoimmune disorders, and is primarily produced by monocytes and neutrophils, said Maristella Steri, PhD, of Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato (Italy), and her associates.

The researchers have named this TNFSF13B variation “BAFF-var.”

Previous genome-wide association studies have identified more than 110 independent signals for MS and 43 for SLE but have not yet delineated the effector mechanisms for most of these associations. To explore these mechanisms in greater detail, Dr. Steri and her associates studied the population in Sardinia, Italy, which has the highest prevalences of MS and SLE in the world.

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A variant in the TNFSF13B gene has been linked to susceptibility to both multiple sclerosis and systemic lupus erythematosus, according to a report published online April 26 in the New England Journal of Medicine.

This gene encodes the cytokine B-cell activating factor (BAFF), which is essential for B-cell activation, differentiation, and survival. BAFF is targeted by agents such as belimumab that are used in the treatment of autoimmune disorders, and is primarily produced by monocytes and neutrophils, said Maristella Steri, PhD, of Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato (Italy), and her associates.

The researchers have named this TNFSF13B variation “BAFF-var.”

Previous genome-wide association studies have identified more than 110 independent signals for MS and 43 for SLE but have not yet delineated the effector mechanisms for most of these associations. To explore these mechanisms in greater detail, Dr. Steri and her associates studied the population in Sardinia, Italy, which has the highest prevalences of MS and SLE in the world.

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[email protected]

A variant in the TNFSF13B gene has been linked to susceptibility to both multiple sclerosis and systemic lupus erythematosus, according to a report published online April 26 in the New England Journal of Medicine.

This gene encodes the cytokine B-cell activating factor (BAFF), which is essential for B-cell activation, differentiation, and survival. BAFF is targeted by agents such as belimumab that are used in the treatment of autoimmune disorders, and is primarily produced by monocytes and neutrophils, said Maristella Steri, PhD, of Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche Monserrato (Italy), and her associates.

The researchers have named this TNFSF13B variation “BAFF-var.”

Previous genome-wide association studies have identified more than 110 independent signals for MS and 43 for SLE but have not yet delineated the effector mechanisms for most of these associations. To explore these mechanisms in greater detail, Dr. Steri and her associates studied the population in Sardinia, Italy, which has the highest prevalences of MS and SLE in the world.

ktsimage/Thinkstock

[email protected]