Multiple Sclerosis Hub

COPENHAGEN—Long walking capacity tests and the Multiple Sclerosis (MS) Walking Scale-12 may be more appropriate than short walking tests (eg, the Timed 25-Foot walk) in detecting clinically meaningful improvement after rehabilitation, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

In addition, walking capacity measures, but not the MS Walking Scale-12, may be more sensitive in detecting change in mildly disabled individuals than in moderately to severely disabled individuals with MS, said Ilse Baert, PhD, post-doctoral researcher in rehabilitation at Hasselt University in Diepenbeek, Belgium.

Patients Assessed Before and After Rehabilitation
To gauge the comparative responsiveness of five walking measures for patients with MS, Dr. Baert and colleagues performed a study at 17 centers in nine countries participating in the European Rehabilitation in MS network for best practices and research. The researchers categorized 290 patients with MS into two subgroups. Patients in the mild disability subgroup had Expanded Disability Status Scale (EDSS) scores of 4 or lower, and patients in the moderate to severe disability subgroup had EDSS scores greater than 4.

At baseline, the investigators assessed participants using the Timed 25-Foot Walk at usual speed, the Timed 25-Foot Walk at a fast speed, a two-minute walk test, a six-minute walk test, and the MS Walking Scale-12. Patients subsequently underwent a rehabilitation program that lasted between three weeks and three months. The researchers assessed patients with all five walking tests again after rehabilitation.

A clinical global impression of change scale, from patients’ and therapists’ perspectives, was chosen as an external criterion for determining responsiveness. To compare the responsiveness of the walking scales, Dr. Baert’s group calculated the area under the receiver operating characteristic curve. An outcome measure was considered not to be responsive if this value was less than 0.5. To provide reference values for clinically meaningful improvement, the researchers calculated the minimally important change, defined as the mean change score in patients who showed a minimally important change according to the external criterion. To quantify the real change (ie, measurement error), the group calculated the smallest real change.

Responsiveness and Clinically Meaningful Changes of Walking Measures
All participants had significantly better walking performance after rehabilitation, regardless of their disability levels. Overall, the MS Walking Scale-12 was the most responsive test, followed by, in order of decreasing responsiveness, the six-minute walk test, the two-minute walk test, the Timed 25-Foot Walk at fast speed, and the Timed 25-Foot Walk at usual speed.

In the mild disability subgroup, the rank of responsiveness of walking tests depended on the perspective. From the patients’ perspective, the two- and six-minute walk tests were more responsive than the Timed 25-Foot Walk test and the MS Walking Scale-12. From the therapists’ perspective, the MS Walking Scale-12 was the most responsive, followed by the Timed 25-Foot Walk at fast speed, the two- and six-minute walk tests, and the Timed 25-Foot Walk at usual speed. In the moderate to severe disability subgroup, the MS Walking Scale-12 and long walking capacity tests were more responsive than short walking tests from the patients’ and therapists’ perspectives.

The investigators found clinically meaningful differences after rehabilitation for three tests. For the two-minute walk test, improvements were 9.6 m from the patients’ perspective and 6.8 m from the therapists’ perspective. For the six-minute walk test, improvement was 21.6 m from the patients’ perspective. Scores on the MS Walking Scale-12 decreased by 10.4 from the patients’ perspective and by 11.4 from the therapists’ perspective. These clinically meaningful improvements exceeded measurement error.

—Erik Greb
Senior Associate Editor

COPENHAGEN—Long walking capacity tests and the Multiple Sclerosis (MS) Walking Scale-12 may be more appropriate than short walking tests (eg, the Timed 25-Foot walk) in detecting clinically meaningful improvement after rehabilitation, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

In addition, walking capacity measures, but not the MS Walking Scale-12, may be more sensitive in detecting change in mildly disabled individuals than in moderately to severely disabled individuals with MS, said Ilse Baert, PhD, post-doctoral researcher in rehabilitation at Hasselt University in Diepenbeek, Belgium.

Patients Assessed Before and After Rehabilitation
To gauge the comparative responsiveness of five walking measures for patients with MS, Dr. Baert and colleagues performed a study at 17 centers in nine countries participating in the European Rehabilitation in MS network for best practices and research. The researchers categorized 290 patients with MS into two subgroups. Patients in the mild disability subgroup had Expanded Disability Status Scale (EDSS) scores of 4 or lower, and patients in the moderate to severe disability subgroup had EDSS scores greater than 4.

At baseline, the investigators assessed participants using the Timed 25-Foot Walk at usual speed, the Timed 25-Foot Walk at a fast speed, a two-minute walk test, a six-minute walk test, and the MS Walking Scale-12. Patients subsequently underwent a rehabilitation program that lasted between three weeks and three months. The researchers assessed patients with all five walking tests again after rehabilitation.

A clinical global impression of change scale, from patients’ and therapists’ perspectives, was chosen as an external criterion for determining responsiveness. To compare the responsiveness of the walking scales, Dr. Baert’s group calculated the area under the receiver operating characteristic curve. An outcome measure was considered not to be responsive if this value was less than 0.5. To provide reference values for clinically meaningful improvement, the researchers calculated the minimally important change, defined as the mean change score in patients who showed a minimally important change according to the external criterion. To quantify the real change (ie, measurement error), the group calculated the smallest real change.

Responsiveness and Clinically Meaningful Changes of Walking Measures
All participants had significantly better walking performance after rehabilitation, regardless of their disability levels. Overall, the MS Walking Scale-12 was the most responsive test, followed by, in order of decreasing responsiveness, the six-minute walk test, the two-minute walk test, the Timed 25-Foot Walk at fast speed, and the Timed 25-Foot Walk at usual speed.

In the mild disability subgroup, the rank of responsiveness of walking tests depended on the perspective. From the patients’ perspective, the two- and six-minute walk tests were more responsive than the Timed 25-Foot Walk test and the MS Walking Scale-12. From the therapists’ perspective, the MS Walking Scale-12 was the most responsive, followed by the Timed 25-Foot Walk at fast speed, the two- and six-minute walk tests, and the Timed 25-Foot Walk at usual speed. In the moderate to severe disability subgroup, the MS Walking Scale-12 and long walking capacity tests were more responsive than short walking tests from the patients’ and therapists’ perspectives.

The investigators found clinically meaningful differences after rehabilitation for three tests. For the two-minute walk test, improvements were 9.6 m from the patients’ perspective and 6.8 m from the therapists’ perspective. For the six-minute walk test, improvement was 21.6 m from the patients’ perspective. Scores on the MS Walking Scale-12 decreased by 10.4 from the patients’ perspective and by 11.4 from the therapists’ perspective. These clinically meaningful improvements exceeded measurement error.

—Erik Greb
Senior Associate Editor

COPENHAGEN—Long walking capacity tests and the Multiple Sclerosis (MS) Walking Scale-12 may be more appropriate than short walking tests (eg, the Timed 25-Foot walk) in detecting clinically meaningful improvement after rehabilitation, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

In addition, walking capacity measures, but not the MS Walking Scale-12, may be more sensitive in detecting change in mildly disabled individuals than in moderately to severely disabled individuals with MS, said Ilse Baert, PhD, post-doctoral researcher in rehabilitation at Hasselt University in Diepenbeek, Belgium.

Patients Assessed Before and After Rehabilitation
To gauge the comparative responsiveness of five walking measures for patients with MS, Dr. Baert and colleagues performed a study at 17 centers in nine countries participating in the European Rehabilitation in MS network for best practices and research. The researchers categorized 290 patients with MS into two subgroups. Patients in the mild disability subgroup had Expanded Disability Status Scale (EDSS) scores of 4 or lower, and patients in the moderate to severe disability subgroup had EDSS scores greater than 4.

At baseline, the investigators assessed participants using the Timed 25-Foot Walk at usual speed, the Timed 25-Foot Walk at a fast speed, a two-minute walk test, a six-minute walk test, and the MS Walking Scale-12. Patients subsequently underwent a rehabilitation program that lasted between three weeks and three months. The researchers assessed patients with all five walking tests again after rehabilitation.

A clinical global impression of change scale, from patients’ and therapists’ perspectives, was chosen as an external criterion for determining responsiveness. To compare the responsiveness of the walking scales, Dr. Baert’s group calculated the area under the receiver operating characteristic curve. An outcome measure was considered not to be responsive if this value was less than 0.5. To provide reference values for clinically meaningful improvement, the researchers calculated the minimally important change, defined as the mean change score in patients who showed a minimally important change according to the external criterion. To quantify the real change (ie, measurement error), the group calculated the smallest real change.

Responsiveness and Clinically Meaningful Changes of Walking Measures
All participants had significantly better walking performance after rehabilitation, regardless of their disability levels. Overall, the MS Walking Scale-12 was the most responsive test, followed by, in order of decreasing responsiveness, the six-minute walk test, the two-minute walk test, the Timed 25-Foot Walk at fast speed, and the Timed 25-Foot Walk at usual speed.

In the mild disability subgroup, the rank of responsiveness of walking tests depended on the perspective. From the patients’ perspective, the two- and six-minute walk tests were more responsive than the Timed 25-Foot Walk test and the MS Walking Scale-12. From the therapists’ perspective, the MS Walking Scale-12 was the most responsive, followed by the Timed 25-Foot Walk at fast speed, the two- and six-minute walk tests, and the Timed 25-Foot Walk at usual speed. In the moderate to severe disability subgroup, the MS Walking Scale-12 and long walking capacity tests were more responsive than short walking tests from the patients’ and therapists’ perspectives.

The investigators found clinically meaningful differences after rehabilitation for three tests. For the two-minute walk test, improvements were 9.6 m from the patients’ perspective and 6.8 m from the therapists’ perspective. For the six-minute walk test, improvement was 21.6 m from the patients’ perspective. Scores on the MS Walking Scale-12 decreased by 10.4 from the patients’ perspective and by 11.4 from the therapists’ perspective. These clinically meaningful improvements exceeded measurement error.

—Erik Greb
Senior Associate Editor

Gray matter, rather than myelin, may be involved in the earliest stages of multiple sclerosis (MS), according to research published September 3 in PLOS One. Gray matter components (eg, axons, neurons, and synapses) may distinguish the CSF proteome of a patient with a true first attack of MS from those of healthy controls and patients with established relapsing-remitting MS.

Nogo receptor was markedly elevated in the CSF of patients with a true first attack of MS, compared with patients with established relapsing-remitting MS and controls, said Steven E. Schutzer, MD, Professor of Medicine at Rutgers University New Jersey Medical School in Newark. Patients with a first attack of MS also had a significant increase of contactin-2/TAG-1, an axonal glycoprotein, in their CSF. Contactin-2/TAG-1 has been reported as an autoimmune target in MS.

Researchers Analyzed CSF From Three Patient Groups
Previous imaging studies have suggested that gray matter changes, and not white matter changes, occur early and predict the development of MS. Other data have conflicted with this idea, however. To determine whether gray matter is involved in early MS, Dr. Schutzer and colleagues collected CSF from three groups of patients. The first group included nine patients with clinically isolated syndrome (CIS) who eventually met diagnostic criteria for MS. The second group included 12 patients with established diagnoses of relapsing-remitting MS according to the McDonald criteria. The third group included six control subjects with no apparent CNS disease.

For the purpose of comparison, the investigators used previously published protein lists generated from two groups of persons with other neurologic diseases and more than 200 healthy controls. The researchers also analyzed a separate group of 10 patients with CIS to compare them with the CIS patients in the study. Dr. Schutzer and colleagues performed protein separation and fractionation on the CSF samples and analyzed them with direct liquid chromatography–mass spectrometry.

Quantities of 20 Proteins Differed Among the Groups
The researchers found 20 proteins that were present in significantly different quantities in patients with CIS, patients with established relapsing-remitting MS, and controls. Nine of these proteins were significantly increased in patients with first-attack CIS, compared with the other two groups. Five proteins were significantly decreased in patients with first-attack CIS, compared with the other groups. The remaining proteins were increased in patients with CIS, compared with patients with relapsing-remitting MS, but decreased compared with controls. Fifteen of the 20 proteins were associated with gray matter.

“There is an increasing literature on the importance of gray matter, neuronal, and axonal involvement in MS, even at very early time points,” said Dr. Schutzer. “Our findings support this [hypothesis] and indicate that axonal, neuronal, and synaptic involvement may be required for the initial presentation of MS. It is interesting in this disease, which is characterized by demyelination as it progresses, that gray matter components may be diagnostically more useful than myelin components at the earliest stages,” he added.

—Erik Greb
Senior Associate Editor

Gray matter, rather than myelin, may be involved in the earliest stages of multiple sclerosis (MS), according to research published September 3 in PLOS One. Gray matter components (eg, axons, neurons, and synapses) may distinguish the CSF proteome of a patient with a true first attack of MS from those of healthy controls and patients with established relapsing-remitting MS.

Nogo receptor was markedly elevated in the CSF of patients with a true first attack of MS, compared with patients with established relapsing-remitting MS and controls, said Steven E. Schutzer, MD, Professor of Medicine at Rutgers University New Jersey Medical School in Newark. Patients with a first attack of MS also had a significant increase of contactin-2/TAG-1, an axonal glycoprotein, in their CSF. Contactin-2/TAG-1 has been reported as an autoimmune target in MS.

Researchers Analyzed CSF From Three Patient Groups
Previous imaging studies have suggested that gray matter changes, and not white matter changes, occur early and predict the development of MS. Other data have conflicted with this idea, however. To determine whether gray matter is involved in early MS, Dr. Schutzer and colleagues collected CSF from three groups of patients. The first group included nine patients with clinically isolated syndrome (CIS) who eventually met diagnostic criteria for MS. The second group included 12 patients with established diagnoses of relapsing-remitting MS according to the McDonald criteria. The third group included six control subjects with no apparent CNS disease.

For the purpose of comparison, the investigators used previously published protein lists generated from two groups of persons with other neurologic diseases and more than 200 healthy controls. The researchers also analyzed a separate group of 10 patients with CIS to compare them with the CIS patients in the study. Dr. Schutzer and colleagues performed protein separation and fractionation on the CSF samples and analyzed them with direct liquid chromatography–mass spectrometry.

Quantities of 20 Proteins Differed Among the Groups
The researchers found 20 proteins that were present in significantly different quantities in patients with CIS, patients with established relapsing-remitting MS, and controls. Nine of these proteins were significantly increased in patients with first-attack CIS, compared with the other two groups. Five proteins were significantly decreased in patients with first-attack CIS, compared with the other groups. The remaining proteins were increased in patients with CIS, compared with patients with relapsing-remitting MS, but decreased compared with controls. Fifteen of the 20 proteins were associated with gray matter.

“There is an increasing literature on the importance of gray matter, neuronal, and axonal involvement in MS, even at very early time points,” said Dr. Schutzer. “Our findings support this [hypothesis] and indicate that axonal, neuronal, and synaptic involvement may be required for the initial presentation of MS. It is interesting in this disease, which is characterized by demyelination as it progresses, that gray matter components may be diagnostically more useful than myelin components at the earliest stages,” he added.

—Erik Greb
Senior Associate Editor

Gray matter, rather than myelin, may be involved in the earliest stages of multiple sclerosis (MS), according to research published September 3 in PLOS One. Gray matter components (eg, axons, neurons, and synapses) may distinguish the CSF proteome of a patient with a true first attack of MS from those of healthy controls and patients with established relapsing-remitting MS.

Nogo receptor was markedly elevated in the CSF of patients with a true first attack of MS, compared with patients with established relapsing-remitting MS and controls, said Steven E. Schutzer, MD, Professor of Medicine at Rutgers University New Jersey Medical School in Newark. Patients with a first attack of MS also had a significant increase of contactin-2/TAG-1, an axonal glycoprotein, in their CSF. Contactin-2/TAG-1 has been reported as an autoimmune target in MS.

Researchers Analyzed CSF From Three Patient Groups
Previous imaging studies have suggested that gray matter changes, and not white matter changes, occur early and predict the development of MS. Other data have conflicted with this idea, however. To determine whether gray matter is involved in early MS, Dr. Schutzer and colleagues collected CSF from three groups of patients. The first group included nine patients with clinically isolated syndrome (CIS) who eventually met diagnostic criteria for MS. The second group included 12 patients with established diagnoses of relapsing-remitting MS according to the McDonald criteria. The third group included six control subjects with no apparent CNS disease.

For the purpose of comparison, the investigators used previously published protein lists generated from two groups of persons with other neurologic diseases and more than 200 healthy controls. The researchers also analyzed a separate group of 10 patients with CIS to compare them with the CIS patients in the study. Dr. Schutzer and colleagues performed protein separation and fractionation on the CSF samples and analyzed them with direct liquid chromatography–mass spectrometry.

Quantities of 20 Proteins Differed Among the Groups
The researchers found 20 proteins that were present in significantly different quantities in patients with CIS, patients with established relapsing-remitting MS, and controls. Nine of these proteins were significantly increased in patients with first-attack CIS, compared with the other two groups. Five proteins were significantly decreased in patients with first-attack CIS, compared with the other groups. The remaining proteins were increased in patients with CIS, compared with patients with relapsing-remitting MS, but decreased compared with controls. Fifteen of the 20 proteins were associated with gray matter.

“There is an increasing literature on the importance of gray matter, neuronal, and axonal involvement in MS, even at very early time points,” said Dr. Schutzer. “Our findings support this [hypothesis] and indicate that axonal, neuronal, and synaptic involvement may be required for the initial presentation of MS. It is interesting in this disease, which is characterized by demyelination as it progresses, that gray matter components may be diagnostically more useful than myelin components at the earliest stages,” he added.

—Erik Greb
Senior Associate Editor

In a small but well-designed study, Schutzer et al used high-resolution mass spectrometry to compare CSF proteins in patients with clinically isolated syndrome (CIS) who eventually developed multiple sclerosis (MS), patients with established relapsing-remitting MS, and controls with no obvious neurologic disease. CSF proteins from patients with CIS were differentially enriched for gray matter components (eg, axons, neurons, and synapses), compared with other groups.

The prominence of gray matter CSF proteins early in MS evolution is not surprising. Sophisticated MRI techniques have allowed investigators to describe gray matter lesions as an early phenomenon in MS, and these lesions may even be more prominent than white matter lesions. Cerebral gray matter is active metabolically; it has greater blood flow, oxygen consumption, and tissue volume than white matter. Axonal pathology is an early and common finding in MS, even in apparently normal white matter, possibly because of immune-mediated inflammatory damage and associated Wallerian degeneration. In addition, gray matter MS pathology can be seen adjacent to meningeal inflammation, and oligodendrocytes and myelinated axons are present in gray matter. These findings are consistent with diffusion of CSF-reactive lymphocytes or their products into cerebral gray matter, and a similar mechanism may occur in white matter across the blood–brain barrier.

However, the concept that CSF gray matter proteins are more enriched in patients with CIS than in those with established MS comes as somewhat of a surprise. While patients with CIS have had only one clinically documented event, there are usually multiple brain lesions that are clinically silent but detected on MRI. These can be considered subclinical relapses because the lesions occur in less eloquent areas or are less destructive. Thus, one does not usually know with certainty when MS actually starts. In this regard, it would be interesting to obtain information on gray matter proteins after a second spinal tap in patients with CIS who later develop definite MS.

Lastly, although gray matter may be affected early in MS, there is insufficient evidence as to whether or not a gray matter protein is an autoimmune trigger in MS.

—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz Professor
of Neurology and Neurosciences
Rutgers, The State University of New Jersey, Newark

In a small but well-designed study, Schutzer et al used high-resolution mass spectrometry to compare CSF proteins in patients with clinically isolated syndrome (CIS) who eventually developed multiple sclerosis (MS), patients with established relapsing-remitting MS, and controls with no obvious neurologic disease. CSF proteins from patients with CIS were differentially enriched for gray matter components (eg, axons, neurons, and synapses), compared with other groups.

The prominence of gray matter CSF proteins early in MS evolution is not surprising. Sophisticated MRI techniques have allowed investigators to describe gray matter lesions as an early phenomenon in MS, and these lesions may even be more prominent than white matter lesions. Cerebral gray matter is active metabolically; it has greater blood flow, oxygen consumption, and tissue volume than white matter. Axonal pathology is an early and common finding in MS, even in apparently normal white matter, possibly because of immune-mediated inflammatory damage and associated Wallerian degeneration. In addition, gray matter MS pathology can be seen adjacent to meningeal inflammation, and oligodendrocytes and myelinated axons are present in gray matter. These findings are consistent with diffusion of CSF-reactive lymphocytes or their products into cerebral gray matter, and a similar mechanism may occur in white matter across the blood–brain barrier.

However, the concept that CSF gray matter proteins are more enriched in patients with CIS than in those with established MS comes as somewhat of a surprise. While patients with CIS have had only one clinically documented event, there are usually multiple brain lesions that are clinically silent but detected on MRI. These can be considered subclinical relapses because the lesions occur in less eloquent areas or are less destructive. Thus, one does not usually know with certainty when MS actually starts. In this regard, it would be interesting to obtain information on gray matter proteins after a second spinal tap in patients with CIS who later develop definite MS.

Lastly, although gray matter may be affected early in MS, there is insufficient evidence as to whether or not a gray matter protein is an autoimmune trigger in MS.

—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz Professor
of Neurology and Neurosciences
Rutgers, The State University of New Jersey, Newark

In a small but well-designed study, Schutzer et al used high-resolution mass spectrometry to compare CSF proteins in patients with clinically isolated syndrome (CIS) who eventually developed multiple sclerosis (MS), patients with established relapsing-remitting MS, and controls with no obvious neurologic disease. CSF proteins from patients with CIS were differentially enriched for gray matter components (eg, axons, neurons, and synapses), compared with other groups.

The prominence of gray matter CSF proteins early in MS evolution is not surprising. Sophisticated MRI techniques have allowed investigators to describe gray matter lesions as an early phenomenon in MS, and these lesions may even be more prominent than white matter lesions. Cerebral gray matter is active metabolically; it has greater blood flow, oxygen consumption, and tissue volume than white matter. Axonal pathology is an early and common finding in MS, even in apparently normal white matter, possibly because of immune-mediated inflammatory damage and associated Wallerian degeneration. In addition, gray matter MS pathology can be seen adjacent to meningeal inflammation, and oligodendrocytes and myelinated axons are present in gray matter. These findings are consistent with diffusion of CSF-reactive lymphocytes or their products into cerebral gray matter, and a similar mechanism may occur in white matter across the blood–brain barrier.

However, the concept that CSF gray matter proteins are more enriched in patients with CIS than in those with established MS comes as somewhat of a surprise. While patients with CIS have had only one clinically documented event, there are usually multiple brain lesions that are clinically silent but detected on MRI. These can be considered subclinical relapses because the lesions occur in less eloquent areas or are less destructive. Thus, one does not usually know with certainty when MS actually starts. In this regard, it would be interesting to obtain information on gray matter proteins after a second spinal tap in patients with CIS who later develop definite MS.

Lastly, although gray matter may be affected early in MS, there is insufficient evidence as to whether or not a gray matter protein is an autoimmune trigger in MS.

—Stuart D. Cook, MD
Ruth Dunietz Kushner and Michael Jay Serwitz Professor
of Neurology and Neurosciences
Rutgers, The State University of New Jersey, Newark

COPENHAGEN—Most, if not all, of the previous claims for association between multiple sclerosis (MS) and month of birth are false positive, according to a study presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). According to researchers, the reported association is more likely to have arisen through confounding factors rather than biology.

Barnaby D. Fiddes, MD, from the Department of Clinical Neurosciences at the University of Cambridge, and colleagues recognized that association studies can generate false positive results if cases and controls are not adequately matched for confounding variables. Given how heterogeneous month of birth is with respect to both year and place of birth, the researchers investigated whether uncompensated variables might underlie the previously reported association between MS and month of birth.

The researchers used publicly available national records for 271 million births in the United Kingdom and Europe to establish birth rates in the general population and their own databases of patients with MS to establish the age and regional origin distribution seen in a typical MS case collection. The investigators also used simulations to make a highly conservative estimate of the false positive rate expected in an analysis of month of birth following the approach used in previously published studies that showed an association between MS and month of birth.

Dr. Fiddes and his research colleagues confirmed that month of birth in the general population shows marked seasonal variation and that this seasonality is highly heterogeneous over time and both between and within countries. Simulations based on UK Government Office Region data showed that failing to correct for within-population variations in month of birth results in a high probability of false positive association.

“We confirmed that in spring months, birth rate shows a positive correlation with latitude and a negative correlation with year of birth, while the reverse is true in winter months,” the researchers reported. “These correlations explain the superficial consistency between month-of-birth studies.”

Dr. Fiddes and colleagues concluded that “although it is impossible to completely exclude any possibility of a month-of-birth effect, our data indicate that previous claims of association between month of birth and MS are almost certain to be false positives.”

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Most, if not all, of the previous claims for association between multiple sclerosis (MS) and month of birth are false positive, according to a study presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). According to researchers, the reported association is more likely to have arisen through confounding factors rather than biology.

Barnaby D. Fiddes, MD, from the Department of Clinical Neurosciences at the University of Cambridge, and colleagues recognized that association studies can generate false positive results if cases and controls are not adequately matched for confounding variables. Given how heterogeneous month of birth is with respect to both year and place of birth, the researchers investigated whether uncompensated variables might underlie the previously reported association between MS and month of birth.

The researchers used publicly available national records for 271 million births in the United Kingdom and Europe to establish birth rates in the general population and their own databases of patients with MS to establish the age and regional origin distribution seen in a typical MS case collection. The investigators also used simulations to make a highly conservative estimate of the false positive rate expected in an analysis of month of birth following the approach used in previously published studies that showed an association between MS and month of birth.

Dr. Fiddes and his research colleagues confirmed that month of birth in the general population shows marked seasonal variation and that this seasonality is highly heterogeneous over time and both between and within countries. Simulations based on UK Government Office Region data showed that failing to correct for within-population variations in month of birth results in a high probability of false positive association.

“We confirmed that in spring months, birth rate shows a positive correlation with latitude and a negative correlation with year of birth, while the reverse is true in winter months,” the researchers reported. “These correlations explain the superficial consistency between month-of-birth studies.”

Dr. Fiddes and colleagues concluded that “although it is impossible to completely exclude any possibility of a month-of-birth effect, our data indicate that previous claims of association between month of birth and MS are almost certain to be false positives.”

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Most, if not all, of the previous claims for association between multiple sclerosis (MS) and month of birth are false positive, according to a study presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). According to researchers, the reported association is more likely to have arisen through confounding factors rather than biology.

Barnaby D. Fiddes, MD, from the Department of Clinical Neurosciences at the University of Cambridge, and colleagues recognized that association studies can generate false positive results if cases and controls are not adequately matched for confounding variables. Given how heterogeneous month of birth is with respect to both year and place of birth, the researchers investigated whether uncompensated variables might underlie the previously reported association between MS and month of birth.

The researchers used publicly available national records for 271 million births in the United Kingdom and Europe to establish birth rates in the general population and their own databases of patients with MS to establish the age and regional origin distribution seen in a typical MS case collection. The investigators also used simulations to make a highly conservative estimate of the false positive rate expected in an analysis of month of birth following the approach used in previously published studies that showed an association between MS and month of birth.

Dr. Fiddes and his research colleagues confirmed that month of birth in the general population shows marked seasonal variation and that this seasonality is highly heterogeneous over time and both between and within countries. Simulations based on UK Government Office Region data showed that failing to correct for within-population variations in month of birth results in a high probability of false positive association.

“We confirmed that in spring months, birth rate shows a positive correlation with latitude and a negative correlation with year of birth, while the reverse is true in winter months,” the researchers reported. “These correlations explain the superficial consistency between month-of-birth studies.”

Dr. Fiddes and colleagues concluded that “although it is impossible to completely exclude any possibility of a month-of-birth effect, our data indicate that previous claims of association between month of birth and MS are almost certain to be false positives.”

—Glenn S. Williams
Vice President/Group Editor

AUSTIN—The 2010 Revised McDonald Diagnostic Criteria for Multiple Sclerosis (MS) may have a higher sensitivity for diagnosing pediatric MS, compared with the 2005 criteria. The revised criteria thus could allow for earlier initiation of disease-modifying therapy, researchers reported at the 2013 Annual Meeting of the Child Neurology Society.

Mitchel T. Williams, MD, Pediatric Neurologist at the Children’s Hospital of Michigan in Detroit, and colleagues conducted a retrospective study of 25 children who had been diagnosed with MS at the Children’s Hospital of Michigan from 2005 through early 2013. The researchers applied the 2005 and 2010 McDonald criteria based on neuroimaging findings and initial clinical presentation. The investigators also analyzed demographic data and compared those data with those of previous pediatric MS cohorts.

The median age at presentation, sex ratio, clinical symptoms, and relapse rate among the participants were comparable to those in previously published data, except for a high rate of African Americans (64%) among the 25 children. The researchers found that the initial MS diagnosis rate based on the 2005 McDonald criteria was 32%, compared with a rate of 92% using the 2010 McDonald criteria. The mean time after initial symptom presentation until the 2005 criteria for MS were met was 5.0 months, compared with 0.7 months for the 2010 McDonald criteria.

“[Our findings] suggest that the 2010 McDonald criteria are a more appropriate tool for the timely diagnosis of pediatric MS,” concluded the researchers.

—Colby Stong
Editor

AUSTIN—The 2010 Revised McDonald Diagnostic Criteria for Multiple Sclerosis (MS) may have a higher sensitivity for diagnosing pediatric MS, compared with the 2005 criteria. The revised criteria thus could allow for earlier initiation of disease-modifying therapy, researchers reported at the 2013 Annual Meeting of the Child Neurology Society.

Mitchel T. Williams, MD, Pediatric Neurologist at the Children’s Hospital of Michigan in Detroit, and colleagues conducted a retrospective study of 25 children who had been diagnosed with MS at the Children’s Hospital of Michigan from 2005 through early 2013. The researchers applied the 2005 and 2010 McDonald criteria based on neuroimaging findings and initial clinical presentation. The investigators also analyzed demographic data and compared those data with those of previous pediatric MS cohorts.

The median age at presentation, sex ratio, clinical symptoms, and relapse rate among the participants were comparable to those in previously published data, except for a high rate of African Americans (64%) among the 25 children. The researchers found that the initial MS diagnosis rate based on the 2005 McDonald criteria was 32%, compared with a rate of 92% using the 2010 McDonald criteria. The mean time after initial symptom presentation until the 2005 criteria for MS were met was 5.0 months, compared with 0.7 months for the 2010 McDonald criteria.

“[Our findings] suggest that the 2010 McDonald criteria are a more appropriate tool for the timely diagnosis of pediatric MS,” concluded the researchers.

—Colby Stong
Editor

AUSTIN—The 2010 Revised McDonald Diagnostic Criteria for Multiple Sclerosis (MS) may have a higher sensitivity for diagnosing pediatric MS, compared with the 2005 criteria. The revised criteria thus could allow for earlier initiation of disease-modifying therapy, researchers reported at the 2013 Annual Meeting of the Child Neurology Society.

Mitchel T. Williams, MD, Pediatric Neurologist at the Children’s Hospital of Michigan in Detroit, and colleagues conducted a retrospective study of 25 children who had been diagnosed with MS at the Children’s Hospital of Michigan from 2005 through early 2013. The researchers applied the 2005 and 2010 McDonald criteria based on neuroimaging findings and initial clinical presentation. The investigators also analyzed demographic data and compared those data with those of previous pediatric MS cohorts.

The median age at presentation, sex ratio, clinical symptoms, and relapse rate among the participants were comparable to those in previously published data, except for a high rate of African Americans (64%) among the 25 children. The researchers found that the initial MS diagnosis rate based on the 2005 McDonald criteria was 32%, compared with a rate of 92% using the 2010 McDonald criteria. The mean time after initial symptom presentation until the 2005 criteria for MS were met was 5.0 months, compared with 0.7 months for the 2010 McDonald criteria.

“[Our findings] suggest that the 2010 McDonald criteria are a more appropriate tool for the timely diagnosis of pediatric MS,” concluded the researchers.

—Colby Stong
Editor

COPENHAGEN—Higher sodium levels are associated with increased clinical and radiologic disease activity in patients with multiple sclerosis (MS), according to study findings presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Because salt has been recently reported to promote the differentiation of pathogenic T cells and worsen disease in an experimental model of MS, investigators sought to determine the relationship between salt consumption and MS disease clinical and radiologic activity.

Mauricio F. Farez, MD, from the Department of Neurology, Institute for Neurological Research Dr Raúl Carrea, Foundation Against Neurological Disease in childhood (FLENI), Buenos Aires, and colleagues measured sodium intake using urine samples from a cohort of 70 patients with relapsing-remitting MS who were followed for two years. During the follow-up, clinical and radiologic assessments were performed every three to six months or in the event of a relapse. The effect of sodium intake on MS disease activity was estimated by regression analysis.

The researchers found a positive correlation between exacerbation rates and sodium intake in a multivariate model adjusted for age, gender, disease duration, smoking status, vitamin D levels, BMI, and treatment. They found an exacerbation rate of 2.75 and 3.95 times higher in patients with medium and high sodium intake, respectively, when compared with the low intake group. In addition, individuals with high sodium intake had 3.4 times greater odds of developing a new lesion on MRI and, on average, had eight more T2 lesions on MRI.

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Higher sodium levels are associated with increased clinical and radiologic disease activity in patients with multiple sclerosis (MS), according to study findings presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Because salt has been recently reported to promote the differentiation of pathogenic T cells and worsen disease in an experimental model of MS, investigators sought to determine the relationship between salt consumption and MS disease clinical and radiologic activity.

Mauricio F. Farez, MD, from the Department of Neurology, Institute for Neurological Research Dr Raúl Carrea, Foundation Against Neurological Disease in childhood (FLENI), Buenos Aires, and colleagues measured sodium intake using urine samples from a cohort of 70 patients with relapsing-remitting MS who were followed for two years. During the follow-up, clinical and radiologic assessments were performed every three to six months or in the event of a relapse. The effect of sodium intake on MS disease activity was estimated by regression analysis.

The researchers found a positive correlation between exacerbation rates and sodium intake in a multivariate model adjusted for age, gender, disease duration, smoking status, vitamin D levels, BMI, and treatment. They found an exacerbation rate of 2.75 and 3.95 times higher in patients with medium and high sodium intake, respectively, when compared with the low intake group. In addition, individuals with high sodium intake had 3.4 times greater odds of developing a new lesion on MRI and, on average, had eight more T2 lesions on MRI.

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Higher sodium levels are associated with increased clinical and radiologic disease activity in patients with multiple sclerosis (MS), according to study findings presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Because salt has been recently reported to promote the differentiation of pathogenic T cells and worsen disease in an experimental model of MS, investigators sought to determine the relationship between salt consumption and MS disease clinical and radiologic activity.

Mauricio F. Farez, MD, from the Department of Neurology, Institute for Neurological Research Dr Raúl Carrea, Foundation Against Neurological Disease in childhood (FLENI), Buenos Aires, and colleagues measured sodium intake using urine samples from a cohort of 70 patients with relapsing-remitting MS who were followed for two years. During the follow-up, clinical and radiologic assessments were performed every three to six months or in the event of a relapse. The effect of sodium intake on MS disease activity was estimated by regression analysis.

The researchers found a positive correlation between exacerbation rates and sodium intake in a multivariate model adjusted for age, gender, disease duration, smoking status, vitamin D levels, BMI, and treatment. They found an exacerbation rate of 2.75 and 3.95 times higher in patients with medium and high sodium intake, respectively, when compared with the low intake group. In addition, individuals with high sodium intake had 3.4 times greater odds of developing a new lesion on MRI and, on average, had eight more T2 lesions on MRI.

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Time to severe disability in progressive multiple sclerosis (MS) is independently accelerated by both pre- and post-progression relapses, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Miguel M. Paz Soldan, MD, and colleagues examined the impact of relapses—both before and after progression onset—on the tempo of post-progression disability accumulation. The researchers studied two cohorts fulfilling McDonald diagnostic criteria for MS: a population-based prevalence cohort from Olmsted County, Minnesota (n = 221), and a clinic-based progressive cohort (n = 859). Progressive disease course was classified as either primary (PPMS), secondary (SPMS), or following a single clinical attack (SAPMS). Disability was assigned per Kurtzke Expanded Disability Status Scale (EDSS). The impact of relapses was studied using a multivariate Cox regression analysis. Gender, age at progression onset, and immunomodulatory medication use were modeled as covariates. Kaplan–Meier analysis was used to generate survival curves to an EDSS score of 6.

Presence of pre-progression relapses (hazard ratio 2.20) predicted shorter time from progression onset to an EDSS score of 6. Post-progression disability accumulation was slowest in patients with PPMS (50% of patients in 10 years), followed by patients with SAPMS (50% in seven years), and fastest in patients with SPMS (50% in four years). Post-progression relapses were more common in patients with SPMS (29.5%) than in patients with SAPMS (10.7%) and patients with PPMS (3.1%), reflecting the pre-progression relapse status in these groups. Ongoing relapses after onset of progressive disease course (17.1%; hazard ratio, 1.48) independently predicted shorter time from progression onset to EDSS score of 6, which was about two years faster. Most post-progression relapses happened within five years (91.6%) after onset of progression and before age 55 (95.2%).

“Our results suggest that continuation of immunomodulation for five years after progression onset or until age 55, whichever comes first, is a reasonable approach in SPMS,” the researchers stated. “However, given the paucity of ongoing relapses, this may not be indicated in SAPMS and PPMS.”

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Time to severe disability in progressive multiple sclerosis (MS) is independently accelerated by both pre- and post-progression relapses, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Miguel M. Paz Soldan, MD, and colleagues examined the impact of relapses—both before and after progression onset—on the tempo of post-progression disability accumulation. The researchers studied two cohorts fulfilling McDonald diagnostic criteria for MS: a population-based prevalence cohort from Olmsted County, Minnesota (n = 221), and a clinic-based progressive cohort (n = 859). Progressive disease course was classified as either primary (PPMS), secondary (SPMS), or following a single clinical attack (SAPMS). Disability was assigned per Kurtzke Expanded Disability Status Scale (EDSS). The impact of relapses was studied using a multivariate Cox regression analysis. Gender, age at progression onset, and immunomodulatory medication use were modeled as covariates. Kaplan–Meier analysis was used to generate survival curves to an EDSS score of 6.

Presence of pre-progression relapses (hazard ratio 2.20) predicted shorter time from progression onset to an EDSS score of 6. Post-progression disability accumulation was slowest in patients with PPMS (50% of patients in 10 years), followed by patients with SAPMS (50% in seven years), and fastest in patients with SPMS (50% in four years). Post-progression relapses were more common in patients with SPMS (29.5%) than in patients with SAPMS (10.7%) and patients with PPMS (3.1%), reflecting the pre-progression relapse status in these groups. Ongoing relapses after onset of progressive disease course (17.1%; hazard ratio, 1.48) independently predicted shorter time from progression onset to EDSS score of 6, which was about two years faster. Most post-progression relapses happened within five years (91.6%) after onset of progression and before age 55 (95.2%).

“Our results suggest that continuation of immunomodulation for five years after progression onset or until age 55, whichever comes first, is a reasonable approach in SPMS,” the researchers stated. “However, given the paucity of ongoing relapses, this may not be indicated in SAPMS and PPMS.”

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Time to severe disability in progressive multiple sclerosis (MS) is independently accelerated by both pre- and post-progression relapses, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Miguel M. Paz Soldan, MD, and colleagues examined the impact of relapses—both before and after progression onset—on the tempo of post-progression disability accumulation. The researchers studied two cohorts fulfilling McDonald diagnostic criteria for MS: a population-based prevalence cohort from Olmsted County, Minnesota (n = 221), and a clinic-based progressive cohort (n = 859). Progressive disease course was classified as either primary (PPMS), secondary (SPMS), or following a single clinical attack (SAPMS). Disability was assigned per Kurtzke Expanded Disability Status Scale (EDSS). The impact of relapses was studied using a multivariate Cox regression analysis. Gender, age at progression onset, and immunomodulatory medication use were modeled as covariates. Kaplan–Meier analysis was used to generate survival curves to an EDSS score of 6.

Presence of pre-progression relapses (hazard ratio 2.20) predicted shorter time from progression onset to an EDSS score of 6. Post-progression disability accumulation was slowest in patients with PPMS (50% of patients in 10 years), followed by patients with SAPMS (50% in seven years), and fastest in patients with SPMS (50% in four years). Post-progression relapses were more common in patients with SPMS (29.5%) than in patients with SAPMS (10.7%) and patients with PPMS (3.1%), reflecting the pre-progression relapse status in these groups. Ongoing relapses after onset of progressive disease course (17.1%; hazard ratio, 1.48) independently predicted shorter time from progression onset to EDSS score of 6, which was about two years faster. Most post-progression relapses happened within five years (91.6%) after onset of progression and before age 55 (95.2%).

“Our results suggest that continuation of immunomodulation for five years after progression onset or until age 55, whichever comes first, is a reasonable approach in SPMS,” the researchers stated. “However, given the paucity of ongoing relapses, this may not be indicated in SAPMS and PPMS.”

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Lipid-specific IgM bands contribute to identify JCV-positive patients at lower risk of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment, according to a report presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Lipid-specific IgM bands are associated with a suboptimal response to interferon beta in patients with MS. Consequently, many patients treated with natalizumab show these antibodies in their CSF. Luisa Maria Villar, PhD, from the Multiple Sclerosis Unit, Department of Immunology, Ramón y Cajal University Hospital, Madrid, and colleagues sought to determine whether PML risk may change in patients with and without these antibodies. The researchers conducted a multicenter study that included 307 patients with MS treated with natalizumab in 20 European hospitals. Anti-JC antibodies were measured in serum by a two-step enzyme-linked immunosorbent assay (ELISA). Lipid-specific IgM bands were measured by isoelectrofocusing and affinity blot in paired serum and CSF samples. Previous treatments with immunosuppressant drugs and treatment duration were recorded.

Nineteen patients developed PML during natalizumab treatment. Only one of them had lipid-specific IgM bands. However, 194 of the 288 patients (67.3%) who did not develop PML had these antibodies. The researchers then analyzed the risk of PML and observed a protective effect of lipid-specific IgM bands (odds ratio, 36.8). As described previously, the absence of anti-JC antibodies also showed a protective effect (odds ratio, 19.4).

To study the effect of the combination of the two variables, Dr. Villar and colleagues further classified anti-JC–positive patients according to lipid-specific IgM bands status. The researchers found that 65% had lipid-specific IgM bands, and 35% (47 patients) lacked these antibodies (anti-JC–positive, lipid-specific IgM band–negative). Seventeen patients of this group developed PML. When PML risk was analyzed, no differences were found between anti-JC–negative patients and anti-JC–positive, lipid-specific IgM band–positive ones. In contrast, the researchers found clear differences between these groups and anti-JC–positive, lipid-specific IgM band–negative patients, which accounted for 90% of PML cases (odds ratio, 59.8).

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Lipid-specific IgM bands contribute to identify JCV-positive patients at lower risk of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment, according to a report presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Lipid-specific IgM bands are associated with a suboptimal response to interferon beta in patients with MS. Consequently, many patients treated with natalizumab show these antibodies in their CSF. Luisa Maria Villar, PhD, from the Multiple Sclerosis Unit, Department of Immunology, Ramón y Cajal University Hospital, Madrid, and colleagues sought to determine whether PML risk may change in patients with and without these antibodies. The researchers conducted a multicenter study that included 307 patients with MS treated with natalizumab in 20 European hospitals. Anti-JC antibodies were measured in serum by a two-step enzyme-linked immunosorbent assay (ELISA). Lipid-specific IgM bands were measured by isoelectrofocusing and affinity blot in paired serum and CSF samples. Previous treatments with immunosuppressant drugs and treatment duration were recorded.

Nineteen patients developed PML during natalizumab treatment. Only one of them had lipid-specific IgM bands. However, 194 of the 288 patients (67.3%) who did not develop PML had these antibodies. The researchers then analyzed the risk of PML and observed a protective effect of lipid-specific IgM bands (odds ratio, 36.8). As described previously, the absence of anti-JC antibodies also showed a protective effect (odds ratio, 19.4).

To study the effect of the combination of the two variables, Dr. Villar and colleagues further classified anti-JC–positive patients according to lipid-specific IgM bands status. The researchers found that 65% had lipid-specific IgM bands, and 35% (47 patients) lacked these antibodies (anti-JC–positive, lipid-specific IgM band–negative). Seventeen patients of this group developed PML. When PML risk was analyzed, no differences were found between anti-JC–negative patients and anti-JC–positive, lipid-specific IgM band–positive ones. In contrast, the researchers found clear differences between these groups and anti-JC–positive, lipid-specific IgM band–negative patients, which accounted for 90% of PML cases (odds ratio, 59.8).

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Lipid-specific IgM bands contribute to identify JCV-positive patients at lower risk of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment, according to a report presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Lipid-specific IgM bands are associated with a suboptimal response to interferon beta in patients with MS. Consequently, many patients treated with natalizumab show these antibodies in their CSF. Luisa Maria Villar, PhD, from the Multiple Sclerosis Unit, Department of Immunology, Ramón y Cajal University Hospital, Madrid, and colleagues sought to determine whether PML risk may change in patients with and without these antibodies. The researchers conducted a multicenter study that included 307 patients with MS treated with natalizumab in 20 European hospitals. Anti-JC antibodies were measured in serum by a two-step enzyme-linked immunosorbent assay (ELISA). Lipid-specific IgM bands were measured by isoelectrofocusing and affinity blot in paired serum and CSF samples. Previous treatments with immunosuppressant drugs and treatment duration were recorded.

Nineteen patients developed PML during natalizumab treatment. Only one of them had lipid-specific IgM bands. However, 194 of the 288 patients (67.3%) who did not develop PML had these antibodies. The researchers then analyzed the risk of PML and observed a protective effect of lipid-specific IgM bands (odds ratio, 36.8). As described previously, the absence of anti-JC antibodies also showed a protective effect (odds ratio, 19.4).

To study the effect of the combination of the two variables, Dr. Villar and colleagues further classified anti-JC–positive patients according to lipid-specific IgM bands status. The researchers found that 65% had lipid-specific IgM bands, and 35% (47 patients) lacked these antibodies (anti-JC–positive, lipid-specific IgM band–negative). Seventeen patients of this group developed PML. When PML risk was analyzed, no differences were found between anti-JC–negative patients and anti-JC–positive, lipid-specific IgM band–positive ones. In contrast, the researchers found clear differences between these groups and anti-JC–positive, lipid-specific IgM band–negative patients, which accounted for 90% of PML cases (odds ratio, 59.8).

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Among patients with multiple sclerosis (MS) in the United States, the rate of relapses was substantially lower in patients who switched from interferon therapy to fingolimod, compared with those who switched to glatiramer acetate, according to a retrospective US claims database analysis presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Niklas Bergvall, PhD, from Novartis Pharma, Basel, Switzerland, and colleagues used US administrative claims data from the IMS PharMetrics Plus Database to compare relapse rates among patients with MS who switched from interferon to fingolimod or glatiramer acetate between October 1, 2010, and September 30, 2011. According to the researchers’ retrospective analysis study protocol, patients needed to switch within 90 days of discontinuing interferon therapy. In addition, patients must have had a diagnosis code for MS within 360 days of the switch (ie, the total period during which the patients were followed).

The occurrence of any type of relapse (identified using a claims-based algorithm) while persistent to fingolimod or glatiramer acetate (period prior to a gap of more than 60 days or switch to another disease-modifying therapy) was measured over 360 days following the switch. The probability of having one or more relapses was estimated using a multivariate logistic regression model, and differences in the rate of relapses were assessed using a multivariate generalized linear model with a negative binomial distribution.

The total sample included 408 patients—198 patients who switched to fingolimod and 210 patients who switched to glatiramer acetate. Before switching, 32.3% and 49.0% of patients had one or more relapses in the fingolimod and glatiramer acetate cohorts, respectively.

In unadjusted analyses, the proportion of patients with one or more relapses during the persistence period was lower for patients treated with fingolimod (16.7%) than for those treated with glatiramer acetate (29.5%) despite a longer mean persistence period (307 vs 282 days for the fingolimod and glatiramer acetate cohorts, respectively). In the persistence period, annualized relapse rates were lower in the fingolimod cohort (0.27) than in the glatiramer acetate cohort (0.55).

After adjusting for baseline differences, the researchers found that patients treated with fingolimod had a 61% reduced probability of having a relapse and 53% fewer relapses per year during the persistence period, compared with patients who switched to glatiramer acetate.

In a related study, Dr. Bergvall and colleagues used the same claims database to compare relapse rates among patients with MS with a history of relapses who were initiated on fingolimod versus interferon or glatiramer acetate.

This study included patients with one or more prescription or administration claims for fingolimod, any interferon, or glatiramer acetate during the same time frame as the previous study (between October 1, 2010, and September 30, 2011). Again, patients had to have an MS diagnosis code and one or more relapses in the 360 days before disease-modifying therapy was initiated and no claim for disease-modifying therapy in the previous 360 days. Patients with prior evidence of fingolimod and another disease-modifying therapy were preferentially assigned to the fingolimod cohort to preserve sample size.

The number of relapses observed while persistent on index disease-modifying therapy (period before a gap of more than 60 days or switch to another disease-modifying therapy) was measured for patients with a 540-day follow-up. The adjusted probability of having one or more relapse was estimated using a logistic regression model, and differences in relapse rates were assessed using a generalized linear model with a negative binomial distribution.

This study included 525 patients (128 on fingolimod and 397 on interferon or glatiramer acetate). Annualized relapse rates in the 360-day pre-index period were 1.70 and 1.26, respectively. In unadjusted analyses, the proportion of patients with one or more relapses during the persistence period was marginally lower in patients treated with fingolimod, compared with interferon or glatiramer acetate (31.3% vs 34.0%), despite a longer mean persistence period (382 vs 341 days, respectively). Annualized relapses over the persistence period were also lower in the fingolimod cohort (0.50), compared with the interferon or glatiramer acetate cohort (0.55) in unadjusted analyses.

After controlling for baseline differences, the investigators found that fingolimod was associated with a 52% reduced probability of experiencing a relapse and 50% fewer relapses, compared with interferon or glatiramer acetate. Point estimates from comparisons of fingolimod versus separate interferon and glatiramer acetate cohorts were identical (50% reduction in relapses).

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Among patients with multiple sclerosis (MS) in the United States, the rate of relapses was substantially lower in patients who switched from interferon therapy to fingolimod, compared with those who switched to glatiramer acetate, according to a retrospective US claims database analysis presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Niklas Bergvall, PhD, from Novartis Pharma, Basel, Switzerland, and colleagues used US administrative claims data from the IMS PharMetrics Plus Database to compare relapse rates among patients with MS who switched from interferon to fingolimod or glatiramer acetate between October 1, 2010, and September 30, 2011. According to the researchers’ retrospective analysis study protocol, patients needed to switch within 90 days of discontinuing interferon therapy. In addition, patients must have had a diagnosis code for MS within 360 days of the switch (ie, the total period during which the patients were followed).

The occurrence of any type of relapse (identified using a claims-based algorithm) while persistent to fingolimod or glatiramer acetate (period prior to a gap of more than 60 days or switch to another disease-modifying therapy) was measured over 360 days following the switch. The probability of having one or more relapses was estimated using a multivariate logistic regression model, and differences in the rate of relapses were assessed using a multivariate generalized linear model with a negative binomial distribution.

The total sample included 408 patients—198 patients who switched to fingolimod and 210 patients who switched to glatiramer acetate. Before switching, 32.3% and 49.0% of patients had one or more relapses in the fingolimod and glatiramer acetate cohorts, respectively.

In unadjusted analyses, the proportion of patients with one or more relapses during the persistence period was lower for patients treated with fingolimod (16.7%) than for those treated with glatiramer acetate (29.5%) despite a longer mean persistence period (307 vs 282 days for the fingolimod and glatiramer acetate cohorts, respectively). In the persistence period, annualized relapse rates were lower in the fingolimod cohort (0.27) than in the glatiramer acetate cohort (0.55).

After adjusting for baseline differences, the researchers found that patients treated with fingolimod had a 61% reduced probability of having a relapse and 53% fewer relapses per year during the persistence period, compared with patients who switched to glatiramer acetate.

In a related study, Dr. Bergvall and colleagues used the same claims database to compare relapse rates among patients with MS with a history of relapses who were initiated on fingolimod versus interferon or glatiramer acetate.

This study included patients with one or more prescription or administration claims for fingolimod, any interferon, or glatiramer acetate during the same time frame as the previous study (between October 1, 2010, and September 30, 2011). Again, patients had to have an MS diagnosis code and one or more relapses in the 360 days before disease-modifying therapy was initiated and no claim for disease-modifying therapy in the previous 360 days. Patients with prior evidence of fingolimod and another disease-modifying therapy were preferentially assigned to the fingolimod cohort to preserve sample size.

The number of relapses observed while persistent on index disease-modifying therapy (period before a gap of more than 60 days or switch to another disease-modifying therapy) was measured for patients with a 540-day follow-up. The adjusted probability of having one or more relapse was estimated using a logistic regression model, and differences in relapse rates were assessed using a generalized linear model with a negative binomial distribution.

This study included 525 patients (128 on fingolimod and 397 on interferon or glatiramer acetate). Annualized relapse rates in the 360-day pre-index period were 1.70 and 1.26, respectively. In unadjusted analyses, the proportion of patients with one or more relapses during the persistence period was marginally lower in patients treated with fingolimod, compared with interferon or glatiramer acetate (31.3% vs 34.0%), despite a longer mean persistence period (382 vs 341 days, respectively). Annualized relapses over the persistence period were also lower in the fingolimod cohort (0.50), compared with the interferon or glatiramer acetate cohort (0.55) in unadjusted analyses.

After controlling for baseline differences, the investigators found that fingolimod was associated with a 52% reduced probability of experiencing a relapse and 50% fewer relapses, compared with interferon or glatiramer acetate. Point estimates from comparisons of fingolimod versus separate interferon and glatiramer acetate cohorts were identical (50% reduction in relapses).

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—Among patients with multiple sclerosis (MS) in the United States, the rate of relapses was substantially lower in patients who switched from interferon therapy to fingolimod, compared with those who switched to glatiramer acetate, according to a retrospective US claims database analysis presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Niklas Bergvall, PhD, from Novartis Pharma, Basel, Switzerland, and colleagues used US administrative claims data from the IMS PharMetrics Plus Database to compare relapse rates among patients with MS who switched from interferon to fingolimod or glatiramer acetate between October 1, 2010, and September 30, 2011. According to the researchers’ retrospective analysis study protocol, patients needed to switch within 90 days of discontinuing interferon therapy. In addition, patients must have had a diagnosis code for MS within 360 days of the switch (ie, the total period during which the patients were followed).

The occurrence of any type of relapse (identified using a claims-based algorithm) while persistent to fingolimod or glatiramer acetate (period prior to a gap of more than 60 days or switch to another disease-modifying therapy) was measured over 360 days following the switch. The probability of having one or more relapses was estimated using a multivariate logistic regression model, and differences in the rate of relapses were assessed using a multivariate generalized linear model with a negative binomial distribution.

The total sample included 408 patients—198 patients who switched to fingolimod and 210 patients who switched to glatiramer acetate. Before switching, 32.3% and 49.0% of patients had one or more relapses in the fingolimod and glatiramer acetate cohorts, respectively.

In unadjusted analyses, the proportion of patients with one or more relapses during the persistence period was lower for patients treated with fingolimod (16.7%) than for those treated with glatiramer acetate (29.5%) despite a longer mean persistence period (307 vs 282 days for the fingolimod and glatiramer acetate cohorts, respectively). In the persistence period, annualized relapse rates were lower in the fingolimod cohort (0.27) than in the glatiramer acetate cohort (0.55).

After adjusting for baseline differences, the researchers found that patients treated with fingolimod had a 61% reduced probability of having a relapse and 53% fewer relapses per year during the persistence period, compared with patients who switched to glatiramer acetate.

In a related study, Dr. Bergvall and colleagues used the same claims database to compare relapse rates among patients with MS with a history of relapses who were initiated on fingolimod versus interferon or glatiramer acetate.

This study included patients with one or more prescription or administration claims for fingolimod, any interferon, or glatiramer acetate during the same time frame as the previous study (between October 1, 2010, and September 30, 2011). Again, patients had to have an MS diagnosis code and one or more relapses in the 360 days before disease-modifying therapy was initiated and no claim for disease-modifying therapy in the previous 360 days. Patients with prior evidence of fingolimod and another disease-modifying therapy were preferentially assigned to the fingolimod cohort to preserve sample size.

The number of relapses observed while persistent on index disease-modifying therapy (period before a gap of more than 60 days or switch to another disease-modifying therapy) was measured for patients with a 540-day follow-up. The adjusted probability of having one or more relapse was estimated using a logistic regression model, and differences in relapse rates were assessed using a generalized linear model with a negative binomial distribution.

This study included 525 patients (128 on fingolimod and 397 on interferon or glatiramer acetate). Annualized relapse rates in the 360-day pre-index period were 1.70 and 1.26, respectively. In unadjusted analyses, the proportion of patients with one or more relapses during the persistence period was marginally lower in patients treated with fingolimod, compared with interferon or glatiramer acetate (31.3% vs 34.0%), despite a longer mean persistence period (382 vs 341 days, respectively). Annualized relapses over the persistence period were also lower in the fingolimod cohort (0.50), compared with the interferon or glatiramer acetate cohort (0.55) in unadjusted analyses.

After controlling for baseline differences, the investigators found that fingolimod was associated with a 52% reduced probability of experiencing a relapse and 50% fewer relapses, compared with interferon or glatiramer acetate. Point estimates from comparisons of fingolimod versus separate interferon and glatiramer acetate cohorts were identical (50% reduction in relapses).

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) is meeting for its 29th Annual Congress in Copenhagen from October 2 to 5. Conference organizers estimate approximately 8,000 participants are attending, making it the world’s premier conference on the science, research, and management of MS.

“I am very pleased about the development of our Congress,” said ECTRIMS President Maria Trojano, MD. The ECTRIMS meeting “has indisputably become the number one international event, as reflected in the record number of submissions from non-European countries and in participant registrations,” she said.

This year’s ECTRIMS Congress features four days of scientific sessions and includes more than 1,000 presentations selected from 1,500 abstracts submitted. The number of abstracts submitted this year represents a 10% increase over last year’s number. The conference program features 29 oral sessions, 14 teaching courses, and 12 satellite symposiums. Thirty companies are exhibiting at the meeting.

Topics that were discussed included genetics and gender differences in MS, including a possible explanation for the increase in women with MS over the past several decades. Also discussed were the mechanism of inflammation and tissue damage and the subsequent remyelination, as well as new scanning techniques for imaging the brain.

Several sessions were devoted to state-of-the-art management of MS with new and future treatments. Treatment of progressive forms of MS was also covered. This year’s ECTRIMS Congress is held in conjunction with the 18th Annual Conference of Rehabilitation in Multiple Sclerosis (RIMS). This joint sponsorship brings opportunities to discuss neuropsychologic challenges and progress in MS rehabilitation. Another special feature of this year’s meeting was the debut of two sessions developed with and for nurses, focusing on how to support families affected by MS.

Hot topics at ECTRIMS 2013 included gene environment interactions, micro RNA, and the effect of the gut microbiome on the susceptibility to MS. A session focused on functional imaging, and researchers debated on whether immunomodulatory treatment can change the natural history of MS.

The 2013 meeting marks the second time that Copenhagen has hosted an ECTRIMS Congress. To commemorate the event, the opening ceremony included a welcome address given by Her Majesty Margrethe II, Queen of Denmark.

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) is meeting for its 29th Annual Congress in Copenhagen from October 2 to 5. Conference organizers estimate approximately 8,000 participants are attending, making it the world’s premier conference on the science, research, and management of MS.

“I am very pleased about the development of our Congress,” said ECTRIMS President Maria Trojano, MD. The ECTRIMS meeting “has indisputably become the number one international event, as reflected in the record number of submissions from non-European countries and in participant registrations,” she said.

This year’s ECTRIMS Congress features four days of scientific sessions and includes more than 1,000 presentations selected from 1,500 abstracts submitted. The number of abstracts submitted this year represents a 10% increase over last year’s number. The conference program features 29 oral sessions, 14 teaching courses, and 12 satellite symposiums. Thirty companies are exhibiting at the meeting.

Topics that were discussed included genetics and gender differences in MS, including a possible explanation for the increase in women with MS over the past several decades. Also discussed were the mechanism of inflammation and tissue damage and the subsequent remyelination, as well as new scanning techniques for imaging the brain.

Several sessions were devoted to state-of-the-art management of MS with new and future treatments. Treatment of progressive forms of MS was also covered. This year’s ECTRIMS Congress is held in conjunction with the 18th Annual Conference of Rehabilitation in Multiple Sclerosis (RIMS). This joint sponsorship brings opportunities to discuss neuropsychologic challenges and progress in MS rehabilitation. Another special feature of this year’s meeting was the debut of two sessions developed with and for nurses, focusing on how to support families affected by MS.

Hot topics at ECTRIMS 2013 included gene environment interactions, micro RNA, and the effect of the gut microbiome on the susceptibility to MS. A session focused on functional imaging, and researchers debated on whether immunomodulatory treatment can change the natural history of MS.

The 2013 meeting marks the second time that Copenhagen has hosted an ECTRIMS Congress. To commemorate the event, the opening ceremony included a welcome address given by Her Majesty Margrethe II, Queen of Denmark.

—Glenn S. Williams
Vice President/Group Editor

COPENHAGEN—The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) is meeting for its 29th Annual Congress in Copenhagen from October 2 to 5. Conference organizers estimate approximately 8,000 participants are attending, making it the world’s premier conference on the science, research, and management of MS.

“I am very pleased about the development of our Congress,” said ECTRIMS President Maria Trojano, MD. The ECTRIMS meeting “has indisputably become the number one international event, as reflected in the record number of submissions from non-European countries and in participant registrations,” she said.

This year’s ECTRIMS Congress features four days of scientific sessions and includes more than 1,000 presentations selected from 1,500 abstracts submitted. The number of abstracts submitted this year represents a 10% increase over last year’s number. The conference program features 29 oral sessions, 14 teaching courses, and 12 satellite symposiums. Thirty companies are exhibiting at the meeting.

Topics that were discussed included genetics and gender differences in MS, including a possible explanation for the increase in women with MS over the past several decades. Also discussed were the mechanism of inflammation and tissue damage and the subsequent remyelination, as well as new scanning techniques for imaging the brain.

Several sessions were devoted to state-of-the-art management of MS with new and future treatments. Treatment of progressive forms of MS was also covered. This year’s ECTRIMS Congress is held in conjunction with the 18th Annual Conference of Rehabilitation in Multiple Sclerosis (RIMS). This joint sponsorship brings opportunities to discuss neuropsychologic challenges and progress in MS rehabilitation. Another special feature of this year’s meeting was the debut of two sessions developed with and for nurses, focusing on how to support families affected by MS.

Hot topics at ECTRIMS 2013 included gene environment interactions, micro RNA, and the effect of the gut microbiome on the susceptibility to MS. A session focused on functional imaging, and researchers debated on whether immunomodulatory treatment can change the natural history of MS.

The 2013 meeting marks the second time that Copenhagen has hosted an ECTRIMS Congress. To commemorate the event, the opening ceremony included a welcome address given by Her Majesty Margrethe II, Queen of Denmark.

—Glenn S. Williams
Vice President/Group Editor