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Seizure Risk Is Nearly Double in Patients With MS
TOPLINE:
, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.
METHODOLOGY:
- The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
- Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
- Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
- They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.
TAKEAWAY:
- A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
- Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
- Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).
IN PRACTICE:
“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.
SOURCE:
The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
LIMITATIONS:
As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.
DISCLOSURES:
Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.
A version of this article appeared on Medscape.com.
TOPLINE:
, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.
METHODOLOGY:
- The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
- Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
- Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
- They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.
TAKEAWAY:
- A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
- Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
- Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).
IN PRACTICE:
“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.
SOURCE:
The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
LIMITATIONS:
As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.
DISCLOSURES:
Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.
A version of this article appeared on Medscape.com.
TOPLINE:
, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.
METHODOLOGY:
- The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
- Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
- Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
- They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.
TAKEAWAY:
- A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
- Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
- Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).
IN PRACTICE:
“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.
SOURCE:
The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
LIMITATIONS:
As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.
DISCLOSURES:
Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.
A version of this article appeared on Medscape.com.
Paramagnetic Rim Lesions Gain Traction as Prognostic Biomarker in MS
WEST PALM BEACH, FLORIDA — , according to one of numerous PRL studies at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“We think this supports other evidence that PRLs are going to be a useful biomarker for MS,” reported Susan Gauthier, DO, an associate professor of neurology and radiology at Weill Cornell University in New York City.
In a simple study, patients with PRLs at baseline were compared with patients without PRLs over a 4-year period, showing that baseline PRLs correlated with worse cognitive function over time.
Of the study cohort, with a median age of 42 years, 5 patients had clinically isolated syndrome (CIS), 81 had relapsing-remitting MS, and 5 had secondary progressive MS. On baseline MRI, 41% of patients had PRLs.
Cognitive function was tracked over time with the Brief International Cognitive Assessment for MS (BICAMS). The components include the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test (BVMT).
Univariate linear model relationships were used to look for a relationship between baseline PRLs and cognitive function. Multiple linear models were performed “with all possible iterations” to further explore the most significant variables. At baseline, no differences were seen in any cognitive test between those with or without PRLs.
Cognitive Function Changes at 4 Years
Those with at least one PRL had significantly lower SDMT (P = 0.046) and BVLT (P = 0.0292) at 4 years. There was no significant difference for CVLT scores.
The findings are consistent with the potential for PRLs to serve “as an imaging marker to identify MS patients at risk for cognitive decline,” said Hannah Schwartz, BA, a mentee of Dr. Gauthier and senior clinical research coordinator in the Department of Neurology at Weill Cornell. Ms. Schwartz presented the data at ACTRIMS Forum Cutting Edge symposium.
Over the past 10 years, there has been a growing body of evidence that the presence of PRLs, which are generally described as a spot of demyelination in the central nervous system surrounded by a rim of iron-laden immune cells such as microglia and macrophages, are prognostically important. The sizable number of studies at the ACTRIMS meeting on PRLs, which so far appear to be unique to MS, suggests the field is maturing.
Routine Measurement of PRLs Is Feasible
One set of data from the CAVS-MS study suggest that routine measurement of this biomarker can be integrated into routine imaging. CAVS-MS is a 2-year international multicenter evaluation of MS biomarkers with 11 participating sites that has collected PRL data on 420 patients.
Overall, PRLs were identified in 39% of these patients. However, patients were divided by typical versus atypical presentation, defined by such factors as an uncharacteristic pattern of attacks, accelerated progression, or radiologically isolated lesions. Among the 201 patients with a typical presentation, at least 1 PRL was found in 53%. Among the 219 with atypical presentations, PRLs were seen in only 26%.
The greater rate of PRLs and the greater number of PRLs per positive patient in the typical presentation group (median 3 vs 2) were highly significant (both P < .0001), reported Brian Renner, MD, a research associate in the neuroimaging program, Department of Neurology, Cedars-Sinai Hospital, Los Angeles.
In this analysis, the PRLs were identified by a single experienced rater with T2- and T1-weighted imaging using 2024 North American Imaging in Multiple Sclerosis (NAIMS) criteria for PRL. These criteria were published earlier this year in Brain.
One message from this study is that “PRL measurement in a large multicenter cohort is feasible,” according to Dr. Renner. This is not only important based on the potential role of PRLs as a prognostic biomarker but also for diagnosis, given the fact that PRLs when present appear to confirm a diagnosis of MS.
Misdiagnosis of MS continues to be a problem, and Dr. Renner said that these appear “to be capable of differentiating MS lesions from non-MS disease mimics.” However, he stated that further validation studies are needed.
Can PRLs Be Prevented or Reversed?
The data on PRLs have generated interest in whether they can be prevented or reversed once they appear. This might be dependent on first determining who is at risk. Another study presented at ACTRIMS suggested that it might not be complex. Lesion size might be critical.
In this study, 233 images were evaluated in 64 patients participating in an observational study at the UMass Memorial Medical Center, Worcester, Massachusetts.
In a univariable analysis, a long list of patient factors, disease characteristics, and imaging characteristics correlated with an increased risk of develop PRLs. These included patient age, disease duration, lesion volume, enhancement pattern (ring vs nodular), and use of disease modifying therapies.
When a regression analysis of these factors was performed, “none of the predictive factors on the univariable analyses were significant after including lesion size in the model,” reported Mustafa Al Gburi, MD, a fellow in neuroimaging at UMass.
While his data did show that exposure to steroids did not appear to reduce risk of developing PRLs, he is now running follow-up to see if specific disease-modifying therapies are more or less preventive for the development of PRL. Because of the limited number of patients and follow-up, it is now too early to tell.
Overall, the risk of PRLs appears to grow substantially at a lesion size of greater than 11 mm, Dr. Al Gburi reported. He believes that this might be “a simple bedside marker to determine patients at future risk of chronic active lesions.”
PRLs might not just be a diagnostic and prognostic tool. Dr. Gauthier said that PRLs are at least a theoretical treatment target. While their immediate promise is in monitoring disease, she thinks the evidence would predict a benefit if PRLs could be prevented or reversed.
Dr. Gauthier reports financial relationships with Genentech, Sanofi-Genzyme, and Mallinckrodt. Dr. Renner and Dr. Al Gburi report no potential conflicts of interest.
WEST PALM BEACH, FLORIDA — , according to one of numerous PRL studies at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“We think this supports other evidence that PRLs are going to be a useful biomarker for MS,” reported Susan Gauthier, DO, an associate professor of neurology and radiology at Weill Cornell University in New York City.
In a simple study, patients with PRLs at baseline were compared with patients without PRLs over a 4-year period, showing that baseline PRLs correlated with worse cognitive function over time.
Of the study cohort, with a median age of 42 years, 5 patients had clinically isolated syndrome (CIS), 81 had relapsing-remitting MS, and 5 had secondary progressive MS. On baseline MRI, 41% of patients had PRLs.
Cognitive function was tracked over time with the Brief International Cognitive Assessment for MS (BICAMS). The components include the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test (BVMT).
Univariate linear model relationships were used to look for a relationship between baseline PRLs and cognitive function. Multiple linear models were performed “with all possible iterations” to further explore the most significant variables. At baseline, no differences were seen in any cognitive test between those with or without PRLs.
Cognitive Function Changes at 4 Years
Those with at least one PRL had significantly lower SDMT (P = 0.046) and BVLT (P = 0.0292) at 4 years. There was no significant difference for CVLT scores.
The findings are consistent with the potential for PRLs to serve “as an imaging marker to identify MS patients at risk for cognitive decline,” said Hannah Schwartz, BA, a mentee of Dr. Gauthier and senior clinical research coordinator in the Department of Neurology at Weill Cornell. Ms. Schwartz presented the data at ACTRIMS Forum Cutting Edge symposium.
Over the past 10 years, there has been a growing body of evidence that the presence of PRLs, which are generally described as a spot of demyelination in the central nervous system surrounded by a rim of iron-laden immune cells such as microglia and macrophages, are prognostically important. The sizable number of studies at the ACTRIMS meeting on PRLs, which so far appear to be unique to MS, suggests the field is maturing.
Routine Measurement of PRLs Is Feasible
One set of data from the CAVS-MS study suggest that routine measurement of this biomarker can be integrated into routine imaging. CAVS-MS is a 2-year international multicenter evaluation of MS biomarkers with 11 participating sites that has collected PRL data on 420 patients.
Overall, PRLs were identified in 39% of these patients. However, patients were divided by typical versus atypical presentation, defined by such factors as an uncharacteristic pattern of attacks, accelerated progression, or radiologically isolated lesions. Among the 201 patients with a typical presentation, at least 1 PRL was found in 53%. Among the 219 with atypical presentations, PRLs were seen in only 26%.
The greater rate of PRLs and the greater number of PRLs per positive patient in the typical presentation group (median 3 vs 2) were highly significant (both P < .0001), reported Brian Renner, MD, a research associate in the neuroimaging program, Department of Neurology, Cedars-Sinai Hospital, Los Angeles.
In this analysis, the PRLs were identified by a single experienced rater with T2- and T1-weighted imaging using 2024 North American Imaging in Multiple Sclerosis (NAIMS) criteria for PRL. These criteria were published earlier this year in Brain.
One message from this study is that “PRL measurement in a large multicenter cohort is feasible,” according to Dr. Renner. This is not only important based on the potential role of PRLs as a prognostic biomarker but also for diagnosis, given the fact that PRLs when present appear to confirm a diagnosis of MS.
Misdiagnosis of MS continues to be a problem, and Dr. Renner said that these appear “to be capable of differentiating MS lesions from non-MS disease mimics.” However, he stated that further validation studies are needed.
Can PRLs Be Prevented or Reversed?
The data on PRLs have generated interest in whether they can be prevented or reversed once they appear. This might be dependent on first determining who is at risk. Another study presented at ACTRIMS suggested that it might not be complex. Lesion size might be critical.
In this study, 233 images were evaluated in 64 patients participating in an observational study at the UMass Memorial Medical Center, Worcester, Massachusetts.
In a univariable analysis, a long list of patient factors, disease characteristics, and imaging characteristics correlated with an increased risk of develop PRLs. These included patient age, disease duration, lesion volume, enhancement pattern (ring vs nodular), and use of disease modifying therapies.
When a regression analysis of these factors was performed, “none of the predictive factors on the univariable analyses were significant after including lesion size in the model,” reported Mustafa Al Gburi, MD, a fellow in neuroimaging at UMass.
While his data did show that exposure to steroids did not appear to reduce risk of developing PRLs, he is now running follow-up to see if specific disease-modifying therapies are more or less preventive for the development of PRL. Because of the limited number of patients and follow-up, it is now too early to tell.
Overall, the risk of PRLs appears to grow substantially at a lesion size of greater than 11 mm, Dr. Al Gburi reported. He believes that this might be “a simple bedside marker to determine patients at future risk of chronic active lesions.”
PRLs might not just be a diagnostic and prognostic tool. Dr. Gauthier said that PRLs are at least a theoretical treatment target. While their immediate promise is in monitoring disease, she thinks the evidence would predict a benefit if PRLs could be prevented or reversed.
Dr. Gauthier reports financial relationships with Genentech, Sanofi-Genzyme, and Mallinckrodt. Dr. Renner and Dr. Al Gburi report no potential conflicts of interest.
WEST PALM BEACH, FLORIDA — , according to one of numerous PRL studies at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
“We think this supports other evidence that PRLs are going to be a useful biomarker for MS,” reported Susan Gauthier, DO, an associate professor of neurology and radiology at Weill Cornell University in New York City.
In a simple study, patients with PRLs at baseline were compared with patients without PRLs over a 4-year period, showing that baseline PRLs correlated with worse cognitive function over time.
Of the study cohort, with a median age of 42 years, 5 patients had clinically isolated syndrome (CIS), 81 had relapsing-remitting MS, and 5 had secondary progressive MS. On baseline MRI, 41% of patients had PRLs.
Cognitive function was tracked over time with the Brief International Cognitive Assessment for MS (BICAMS). The components include the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test (BVMT).
Univariate linear model relationships were used to look for a relationship between baseline PRLs and cognitive function. Multiple linear models were performed “with all possible iterations” to further explore the most significant variables. At baseline, no differences were seen in any cognitive test between those with or without PRLs.
Cognitive Function Changes at 4 Years
Those with at least one PRL had significantly lower SDMT (P = 0.046) and BVLT (P = 0.0292) at 4 years. There was no significant difference for CVLT scores.
The findings are consistent with the potential for PRLs to serve “as an imaging marker to identify MS patients at risk for cognitive decline,” said Hannah Schwartz, BA, a mentee of Dr. Gauthier and senior clinical research coordinator in the Department of Neurology at Weill Cornell. Ms. Schwartz presented the data at ACTRIMS Forum Cutting Edge symposium.
Over the past 10 years, there has been a growing body of evidence that the presence of PRLs, which are generally described as a spot of demyelination in the central nervous system surrounded by a rim of iron-laden immune cells such as microglia and macrophages, are prognostically important. The sizable number of studies at the ACTRIMS meeting on PRLs, which so far appear to be unique to MS, suggests the field is maturing.
Routine Measurement of PRLs Is Feasible
One set of data from the CAVS-MS study suggest that routine measurement of this biomarker can be integrated into routine imaging. CAVS-MS is a 2-year international multicenter evaluation of MS biomarkers with 11 participating sites that has collected PRL data on 420 patients.
Overall, PRLs were identified in 39% of these patients. However, patients were divided by typical versus atypical presentation, defined by such factors as an uncharacteristic pattern of attacks, accelerated progression, or radiologically isolated lesions. Among the 201 patients with a typical presentation, at least 1 PRL was found in 53%. Among the 219 with atypical presentations, PRLs were seen in only 26%.
The greater rate of PRLs and the greater number of PRLs per positive patient in the typical presentation group (median 3 vs 2) were highly significant (both P < .0001), reported Brian Renner, MD, a research associate in the neuroimaging program, Department of Neurology, Cedars-Sinai Hospital, Los Angeles.
In this analysis, the PRLs were identified by a single experienced rater with T2- and T1-weighted imaging using 2024 North American Imaging in Multiple Sclerosis (NAIMS) criteria for PRL. These criteria were published earlier this year in Brain.
One message from this study is that “PRL measurement in a large multicenter cohort is feasible,” according to Dr. Renner. This is not only important based on the potential role of PRLs as a prognostic biomarker but also for diagnosis, given the fact that PRLs when present appear to confirm a diagnosis of MS.
Misdiagnosis of MS continues to be a problem, and Dr. Renner said that these appear “to be capable of differentiating MS lesions from non-MS disease mimics.” However, he stated that further validation studies are needed.
Can PRLs Be Prevented or Reversed?
The data on PRLs have generated interest in whether they can be prevented or reversed once they appear. This might be dependent on first determining who is at risk. Another study presented at ACTRIMS suggested that it might not be complex. Lesion size might be critical.
In this study, 233 images were evaluated in 64 patients participating in an observational study at the UMass Memorial Medical Center, Worcester, Massachusetts.
In a univariable analysis, a long list of patient factors, disease characteristics, and imaging characteristics correlated with an increased risk of develop PRLs. These included patient age, disease duration, lesion volume, enhancement pattern (ring vs nodular), and use of disease modifying therapies.
When a regression analysis of these factors was performed, “none of the predictive factors on the univariable analyses were significant after including lesion size in the model,” reported Mustafa Al Gburi, MD, a fellow in neuroimaging at UMass.
While his data did show that exposure to steroids did not appear to reduce risk of developing PRLs, he is now running follow-up to see if specific disease-modifying therapies are more or less preventive for the development of PRL. Because of the limited number of patients and follow-up, it is now too early to tell.
Overall, the risk of PRLs appears to grow substantially at a lesion size of greater than 11 mm, Dr. Al Gburi reported. He believes that this might be “a simple bedside marker to determine patients at future risk of chronic active lesions.”
PRLs might not just be a diagnostic and prognostic tool. Dr. Gauthier said that PRLs are at least a theoretical treatment target. While their immediate promise is in monitoring disease, she thinks the evidence would predict a benefit if PRLs could be prevented or reversed.
Dr. Gauthier reports financial relationships with Genentech, Sanofi-Genzyme, and Mallinckrodt. Dr. Renner and Dr. Al Gburi report no potential conflicts of interest.
FROM ACRIMS FORUM 2024
Depression, constipation, UTIs early signs of MS?
However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.
“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
Retracing MS Origins
The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.
Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.
Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.
After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:
- Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
- Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
- Constipation (OR, 1.5; 95% CI, 1.27-1.78)
- Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
- UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)
However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.
“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.
“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.
A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.
It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
Preventing Disease Evolution
In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.
“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.
“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.
The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.
A version of this article appeared on Medscape.com.
However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.
“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
Retracing MS Origins
The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.
Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.
Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.
After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:
- Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
- Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
- Constipation (OR, 1.5; 95% CI, 1.27-1.78)
- Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
- UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)
However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.
“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.
“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.
A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.
It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
Preventing Disease Evolution
In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.
“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.
“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.
The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.
A version of this article appeared on Medscape.com.
However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.
“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
Retracing MS Origins
The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.
Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.
Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.
After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:
- Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
- Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
- Constipation (OR, 1.5; 95% CI, 1.27-1.78)
- Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
- UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)
However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.
“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.
“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.
A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.
It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
Preventing Disease Evolution
In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.
“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.
“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.
The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.
A version of this article appeared on Medscape.com.
FROM NEUROLOGY
Subcutaneous ocrelizumab, ofatumumab ‘reassuring’ in MS
MILAN – , suggest results from two clinical trials.
For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).
After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.
The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.
The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).
Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Anti-CD20–naive
OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.
They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.
In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.
The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.
By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.
The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.
However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.
Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”
He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
Efficacy maintained
The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.
After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.
Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.
The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.
At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.
The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.
They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
Reassuring results
“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.
“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.
“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.
“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.
In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”
OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.
A version of this article first appeared on Medscape.com.
MILAN – , suggest results from two clinical trials.
For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).
After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.
The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.
The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).
Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Anti-CD20–naive
OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.
They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.
In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.
The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.
By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.
The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.
However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.
Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”
He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
Efficacy maintained
The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.
After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.
Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.
The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.
At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.
The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.
They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
Reassuring results
“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.
“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.
“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.
“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.
In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”
OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.
A version of this article first appeared on Medscape.com.
MILAN – , suggest results from two clinical trials.
For OCARINA II, more than 325 patients with MS were randomly assigned to either subcutaneous or intravenous treatment with the anti-CD20 monoclonal antibody ocrelizumab (Ocrevus).
After 24 weeks, the presence of lesions on imaging and the occurrence of clinical remissions were almost completely suppressed by both treatments albeit with a higher rate of mild to moderate injection reactions with subcutaneous administration.
The study “makes me feel pretty comfortable that regardless of where you’re delivering the therapy, IV or subcutaneously, it’s getting in there and doing the job that we want it to do,” said lead author Scott D. Newsome, DO, director, Stiff Person Syndrome Center, Johns Hopkins University, Baltimore.
The second study, OLIKOS, involved just over 100 patients with relapsing MS who had previously been treated with an anti-CD20 monoclonal antibody and were switched to subcutaneous therapy with another: ofatumumab (Arzerra).
Le H. Hua, MD, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues report that the novel treatment maintained clinical efficacy in all patients, with no safety concerns and no changes in serum immunoglobulin levels.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Anti-CD20–naive
OCARINA II involved patients aged 18-65 years with relapsing or primary progressive MS who had never received ocrelizumab or any other anti-CD20 therapy and had an Expanded Disability Status Scale (EDSS) score of 0.0-6.5.
They were randomly assigned to subcutaneous or IV ocrelizumab as a first dose. At week 24, all patients were scheduled to receive subcutaneous ocrelizumab every 24 weeks up to week 96.
In all, 326 patients were randomly assigned to the two treatment arms. They had a mean age of approximately 40 years, and 59.3%-65.3% were women. The mean time since symptom onset was 6.8-7.7 years, and the mean EDSS score at baseline was 2.5-3.0. The majority (89.8%-89.0%) had relapsing MS.
The results showed that subcutaneous and IV administration led to similar exposure to ocrelizumab, and both resulted in rapid reduction in CD19+ B-cell counts.
By week 24, the mean number of lesions on MRI reduced to zero, resulting in “near-complete suppression” of disease activity, the team says, which was reflected in 99% of patients have no clinical evidence of relapse.
The overall adverse event rate was higher with subcutaneous vs. IV administration of ocrelizumab, at 73.7% vs. 45.8%, driven by both local and systemic injection reactions, which were mild to moderate in nature.
However, a similar proportion of patients in the subcutaneous and IV arms experienced serious adverse events, at 2.5% and 3.4%, respectively.
Crucially, the patients were “overwhelmingly positive” about the subcutaneous administration, Dr. Newsome said, and at his institution, “all the patients want to continue, if and when this gets approved.”
He said that, overall, he would like to have both routes available “because, coming down to patient preference, some prefer to have IV over subcutaneous in general, and that could be for a variety of reasons, so I would love to have as many different routes of administration as possible to offer.”
Efficacy maintained
The OLIKOS trial included patients aged 18-60 years with relapsing MS who had received at least two consecutive courses of anti-CD20 therapy with either ocrelizumab or rituximab and who had an EDSS score ≤ 5.5 and were neurologically stable.
After an initial loading regimen of subcutaneous ofatumumab on days 1, 7, and 14, the patients continued open-label subcutaneous ofatumumab once a month for 12 months, with assessments carried out at baseline and at 1, 6, and 12 months.
Of 142 patients assessed, 102 received treatment and were evaluated. Their mean age was 43.5 years, and 67.6% were women. The mean baseline EDSS score was 2.9, and the mean disease duration since diagnosis was 9.4 years.
The vast majority of patients (99.0%) had previously received ocrelizumab for an average duration of 26.7 months.
At this interim analysis, 100% of the 77 patients with follow-up MRI met the primary endpoint at month 6 of no change or a reduction in the number of lesions.
The team says there were “no new safety signals,” with 75.5% of patients experiencing a treatment-emergent adverse event, but only 1.0% having a serious adverse event. Injection site reactions occurred in 7.8%; 15.7% had a systemic injection reaction.
They also report that there were no changes in IgG and IgM concentrations between baseline and follow-up, which remained within normal reference ranges.
Reassuring results
“It’s exciting to see reassuring results from clinical studies of two high-efficacy therapies for multiple sclerosis, especially given their route of administration,” commented Julie Fiol, LMSW, BSN, RN, MSCN, associate vice president of Clinical Innovation and Strategy for the U.S. National MS Society.
“Subcutaneous injections allow people with multiple sclerosis more flexibility when selecting a therapy that matches their lifestyle and preferences,” she said in an interview.
“Adherence to therapy is critical in multiple sclerosis, and additional options for route of administration and site of care enhance the likelihood that someone with multiple sclerosis will find a medication that effectively manages their disease and fits into their lifestyle,” Dr. Fiol explained.
“Subcutaneous injections also have the potential to be more affordable as they could be administered at home or over a shorter duration than an infused medication,” she noted.
In terms of these two particular studies, she added, “it’s reassuring to see that the safety and efficacy of subcutaneous ocrelizumab was similar to intravenous. It was also reassuring to see those who switched from ocrelizumab and rituximab to ofatumumab remained clinically stable.”
OCARINA II was supported by F. Hoffmann-La Roche. OLIKOS was supported by Novartis. Dr. Newsome declares relationships with Biogen, Genentech, Bristol-Myers Squibb, EMD Serono, Greenwich Biosciences, Horizon Therapeutics, Novartis, Roche, and TG Therapeutics and institutional relationships with Biogen, Lundbeck, Roche, Genentech, National MS Society, The Stiff Person Syndrome Research Foundation, Department of Defense, and the Patient-Centered Outcomes Research Institute. Dr. Hua declares relationships with Alexion, Biogen, Bristol-Meyers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, Horizon Therapeutics, and Novartis. Other authors also declare relationships.
A version of this article first appeared on Medscape.com.
AT ECTRIMS 2023
‘Frame running’ may help boost physical activity in MS
MILAN – , a pilot study suggests.
“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.
Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.
“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.
It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Dearth of exercise opportunities
The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.
This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”
In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.
The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.
The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.
The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
The camaraderie of physical activity
With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.
The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).
There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.
A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.
The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
Mix of physical interventions
Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.
He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”
However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”
With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”
Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.
Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”
The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MILAN – , a pilot study suggests.
“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.
Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.
“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.
It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Dearth of exercise opportunities
The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.
This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”
In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.
The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.
The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.
The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
The camaraderie of physical activity
With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.
The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).
There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.
A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.
The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
Mix of physical interventions
Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.
He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”
However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”
With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”
Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.
Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”
The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MILAN – , a pilot study suggests.
“Frame running” uses a three-wheeled frame with a saddle and body supports but no pedals to allow individuals with disabilities and balance impairments to walk and run under their own power.
Eight individuals with multiple sclerosis and moderate to severe walking impairments took part in a 12-week frame running intervention, which improved both objective physical performance and patient-reported outcomes measures.
“Frame running presents a feasible and enjoyable exercise option for people with multiple sclerosis,” lead author Gary McEwan, PhD, research fellow at the Centre for Health, Activity and Rehabilitation Research at Queen Margaret University, Edinburgh, and colleagues conclude.
It may, they add, “have potential to improve measures of physical function and the ability to perform mobility-related daily activities.”
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS Meeting.
Dearth of exercise opportunities
The authors note regular physical activity and exercise are “amongst the most important adjunct therapies for managing the symptoms of multiple sclerosis,” and yet people with the disease are significantly less physically active than the general population.
This is particularly the case for individuals at the upper end of the disability spectrum, they continue, and may reflect the “relative dearth of exercise opportunities that are suitable for those with more severe mobility impairments.”
In recent years, frame running has emerged as a form of exercise that allows individuals with walking difficulties to engage in moderate to vigorous physical activity in a safe manner, but its feasibility in multiple sclerosis has not been investigated.
The researchers recruited people with multiple sclerosis who had moderate to severe walking impairments to take part in a 12-week frame running intervention, comprising a 1-hour session every week.
The 6-minute frame running test (6MFRT) and an adapted shuttle frame running test (SFRT) were used to assess physical function at baseline and after the intervention. Recruitment, retention, and attendance rates were recorded.
The participants also completed a series of patient-reported outcome measures, alongside the Canadian Occupational Performance Measure, to calculate self-perceived abilities in activities of daily living, and semistructured interviews to capture their experiences of the intervention.
The camaraderie of physical activity
With six females and two males enrolled in the study, the team reported that the recruitment rate was 47.1%, the retention rate was 75%, and attendance was 86.7%. No adverse events were reported, they note.
The results indicate there were improvements in performance on the physical measures, with small effect sizes on both the 6MFRT (d = 0.37) and the SFRT (d = 0.30).
There were also improvements on the Multiple Sclerosis Walking Scale (d = 0.27), the Fatigue Scale for Motor and Cognitive Functions (d = 0.20), and the Exercise Self-Efficacy Scale (d = 0.46), again with small effect sizes.
A medium effect size was seen for improvements on the Godin Leisure Time Exercise Questionnaire (d = 0.73), and 80% of the participants reported “changes in performance and in satisfaction with their activities of daily living,” the team says.
The qualitative data also suggested the patients found frame running to be “safe and enjoyable,” with key highlights being the “social aspect and camaraderie developed amongst participants.”
Mix of physical interventions
Approached for comment, Robert Motl, MD, professor of kinesiology and nutrition, College of Applied Health Sciences, University of Illinois at Chicago, said it “makes a lot of sense” that frame running can improve walking-related outcomes.
He told this news organization that, “for people who have balance-related problems, using their legs in that rhythmical way could really have some great benefits for walking.”
However, Dr. Motl said he is a “little more skeptical about the benefits for balance, because to improve balance you have to be doing something that challenges upright posture.”
With the frame, “I don’t think you’re having to regulate upright posture while you’re doing that intervention, because you have stability with three points and the ground,” he said. “So, I wonder a little bit about that as an outcome.”
Dr. Motl nevertheless underlined that walking can certainly improve physical activity, “and all the other things like vascular function, cardiovascular fitness,” and so on.
Consequently, frame running “could be part of the mix of things for people who are having a disability, particularly individuals who have some balance dysfunction and [for whom] ambulating might put them at risk of falling.”
The study was supported by a research grant from the Multiple Sclerosis Society UK. The study authors and Dr. Modl report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2023
MS, DMTs, and pregnancy: Beware of over-caution regarding treatment
MILAN – The news about multiple sclerosis (MS) and child-bearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.
Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication – or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.
Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.
While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”
But some treatments may be harmful to the fetus, she said. Teriflunomide must be stopped before pregnancy. Natalizumab and fingolimod-siponimod raise the risk of rebound, and alternate drugs should be considered before pregnancy. However, anti–CD 20 drugs and cladribine “may be a relevant option because their use before pregnancy may provide effective disease control without exposing the fetus or the baby.”
Should women be on MS drugs at all during pregnancy, a period when MS typically wanes? “The recommendation is to discontinue disease-modifying therapy before conception,” Dr. Leray said. “However, we know now that some DMTs can be used safely during pregnancy, especially injectables.” Specifically, beta interferon and glatiramer acetate can be used safely during pregnancy, she said.
The biggest hurdle comes after pregnancy, when women face a high risk of MS rebound. The relapse rate has fallen in recent years from about 30% to 11%-14%, Dr. Leray said, possibly because of the rise of more effective treatment. But the risk, she said, is still significant.
What can clinicians do to avert relapse? According to Dr. Leray, research has failed to support several possible alternatives to DMTs – high-dose corticosteroids, intravenous immunoglobulin, and hormonal treatment. “There was no evidence of efficacy of any of these strategies, both in randomized clinical trials and in real-world studies.”
For now, it seems best to restart DMTs as soon as possible after delivery, Dr. Leray said. She urged colleagues to keep in mind that it takes about 3 months for DMTs to reach full efficacy – and research suggests the highest risk of relapse is during the first 3 months after delivery. “That has to be taken into account in the therapeutic strategy,” she said.
Dr. Leray reports consulting/lecture/travel grants from Biogen, Genzyme, MedDay, Merck, Novartis, and Roche.
MILAN – The news about multiple sclerosis (MS) and child-bearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.
Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication – or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.
Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.
While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”
But some treatments may be harmful to the fetus, she said. Teriflunomide must be stopped before pregnancy. Natalizumab and fingolimod-siponimod raise the risk of rebound, and alternate drugs should be considered before pregnancy. However, anti–CD 20 drugs and cladribine “may be a relevant option because their use before pregnancy may provide effective disease control without exposing the fetus or the baby.”
Should women be on MS drugs at all during pregnancy, a period when MS typically wanes? “The recommendation is to discontinue disease-modifying therapy before conception,” Dr. Leray said. “However, we know now that some DMTs can be used safely during pregnancy, especially injectables.” Specifically, beta interferon and glatiramer acetate can be used safely during pregnancy, she said.
The biggest hurdle comes after pregnancy, when women face a high risk of MS rebound. The relapse rate has fallen in recent years from about 30% to 11%-14%, Dr. Leray said, possibly because of the rise of more effective treatment. But the risk, she said, is still significant.
What can clinicians do to avert relapse? According to Dr. Leray, research has failed to support several possible alternatives to DMTs – high-dose corticosteroids, intravenous immunoglobulin, and hormonal treatment. “There was no evidence of efficacy of any of these strategies, both in randomized clinical trials and in real-world studies.”
For now, it seems best to restart DMTs as soon as possible after delivery, Dr. Leray said. She urged colleagues to keep in mind that it takes about 3 months for DMTs to reach full efficacy – and research suggests the highest risk of relapse is during the first 3 months after delivery. “That has to be taken into account in the therapeutic strategy,” she said.
Dr. Leray reports consulting/lecture/travel grants from Biogen, Genzyme, MedDay, Merck, Novartis, and Roche.
MILAN – The news about multiple sclerosis (MS) and child-bearing in women is largely good, a researcher told colleagues at the 9th Joint ECTRIMS-ACTRIMS Meeting. However, there are still uncertainties about the timing of medical treatment for MS before, during, and after pregnancy.
Epidemiologist Emmanuelle Leray, PhD, of French School of Public Health in Rennes, urged neurologists to not be too eager to take women off medication – or too slow to put them back on it. “MS should not be undertreated due to a desire for pregnancy, as there are several options that are possible and compatible with pregnancy,” she said. As for after pregnancy, when women face a well-known high risk of MS rebound, “we can reasonably assume that women with active MS need to be advised to restart rapid, highly effective DMT [disease-modifying therapy] soon after delivery,” she said.
Women are more likely than men to develop MS, and they often do so during child-bearing years. Pregnancy among women with MS has become more common over the years: A 2018 Neurology study examined U.S. data from 2006 to 2014 and reported that the annual adjusted proportion of women with MS and pregnancy increased from 7.91% to 9.47%.
While it appears that women with MS get pregnant less often than the age-matched general population, that “doesn’t mean that fertility is impaired. It probably rather reflects the impact of an early diagnosis of MS on associated consequences regarding psychological and physical impact,” Dr. Leray said. “Regarding pregnancy outcomes, there is no evidence of an increased risk of prematurity or adverse neonatal outcomes. That’s why we can assume that multiple sclerosis will not impact the course of pregnancy and does not make a pregnancy at-risk.”
But some treatments may be harmful to the fetus, she said. Teriflunomide must be stopped before pregnancy. Natalizumab and fingolimod-siponimod raise the risk of rebound, and alternate drugs should be considered before pregnancy. However, anti–CD 20 drugs and cladribine “may be a relevant option because their use before pregnancy may provide effective disease control without exposing the fetus or the baby.”
Should women be on MS drugs at all during pregnancy, a period when MS typically wanes? “The recommendation is to discontinue disease-modifying therapy before conception,” Dr. Leray said. “However, we know now that some DMTs can be used safely during pregnancy, especially injectables.” Specifically, beta interferon and glatiramer acetate can be used safely during pregnancy, she said.
The biggest hurdle comes after pregnancy, when women face a high risk of MS rebound. The relapse rate has fallen in recent years from about 30% to 11%-14%, Dr. Leray said, possibly because of the rise of more effective treatment. But the risk, she said, is still significant.
What can clinicians do to avert relapse? According to Dr. Leray, research has failed to support several possible alternatives to DMTs – high-dose corticosteroids, intravenous immunoglobulin, and hormonal treatment. “There was no evidence of efficacy of any of these strategies, both in randomized clinical trials and in real-world studies.”
For now, it seems best to restart DMTs as soon as possible after delivery, Dr. Leray said. She urged colleagues to keep in mind that it takes about 3 months for DMTs to reach full efficacy – and research suggests the highest risk of relapse is during the first 3 months after delivery. “That has to be taken into account in the therapeutic strategy,” she said.
Dr. Leray reports consulting/lecture/travel grants from Biogen, Genzyme, MedDay, Merck, Novartis, and Roche.
AT ECTRIMS 2023
Wearable devices show promise in monitoring multiple sclerosis
MILAN – , suggests a pilot study.
Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.
The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.
Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Leveraging big data to improve outcomes
The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.
For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.
Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.
To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.
This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
Feasible with high levels of confidence
Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.
The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.
The team reports that the data from the tool kit “are in line with those reported in the literature.”
It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.
Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.
The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.
Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.
They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
Reducing daily step count
Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”
She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.
“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”
The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
MILAN – , suggests a pilot study.
Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.
The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.
Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Leveraging big data to improve outcomes
The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.
For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.
Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.
To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.
This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
Feasible with high levels of confidence
Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.
The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.
The team reports that the data from the tool kit “are in line with those reported in the literature.”
It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.
Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.
The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.
Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.
They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
Reducing daily step count
Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”
She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.
“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”
The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
MILAN – , suggests a pilot study.
Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.
The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.
Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.
The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
Leveraging big data to improve outcomes
The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.
For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.
Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.
To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.
This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
Feasible with high levels of confidence
Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.
The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.
The team reports that the data from the tool kit “are in line with those reported in the literature.”
It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.
Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.
The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.
Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.
They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
Reducing daily step count
Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”
She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.
“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”
The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
NMO: Study says double diagnoses with MS are common
MILAN – , according to a poster presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
“There is a lack of education in differentiating between MS and NMO even in the medical community, which may result in a high misdiagnosis rate,” said study lead author Ka-Ho Wong, MBA, of the University of Utah, Salt Lake City, in an interview.
“NMO was recognized in the late 1800s and was historically thought to be a variant of MS until 1999,” said Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, both in Boston, in an interview.
“They are both relapsing inflammatory disorders of the central nervous system with similarities in symptoms of weakness, numbness, mobility problem, vision defects, pain and fatigue,” said Dr. Levy, who did not take part in the new study. “A blood test for NMO was developed in 2004 and improved over time to the point that it can now reliably distinguish NMO from MS.”
As for therapy, “recent research has confirmed the two conditions are immunologically different and respond to different treatment,” Dr. Levy said. “The treatments developed for MS, especially from the 1990s, are harmful in NMO so it is important to make the diagnosis correctly.”
He added that “we do not recognize overlap between NMO or MS – it’s one or the other.”
Exploring the reasons for misdiagnosis
Mr. Wong, the present study’s lead author, said he and a research team launched the new study to better understand who gets misdiagnosed. “We know that almost 50% of the individuals get misdiagnosed at some point. However, what we don’t know yet is if the influencing factors are social determinants of health or if there are other causes.”
For the study, Mr. Wong and colleagues analyzed data from TriNetX, a health research network with access to medical records from 61 U.S. health care organizations. providing access to electronic medical records that includes sixty-one health care organizations (HCOs) in the United States.
ICD-10 coding statistics from 2008 to 2022 identified 7,657 patients with diagnoses for NMO. Of those, 4,040 (53%) only had diagnoses for NMO, and the rest (3,617, 47%) had diagnoses for both NMO and MS.
The researchers focused on 1,265 patients who had been coded for both diagnoses and had at least three clinical visits. They determined that a patient was misdiagnosed when they had three consecutive diagnoses of the same type. “For example, if they had MS but got misdiagnosed as NMO, once they are confirmed as MS they must have three or more consecutive diagnosis of MS to be considered as misdiagnosed,” Mr. Wong said.
Of the 1,265 subjects, the researchers determined that 308 (24%) had NMO but had been misdiagnosed as having MS, 189 (15%) had MS but were misdiagnosed as having NMO, and 768 (61%) were interchangeably diagnosed with the two conditions over time.
Among these three groups, 70.8%, 73.1%, and 78.4% were female, respectively; and 59.4%, 52.9%, and 53.0% were White, respectively. The percentages of Black patients were 17.2%, 24.3%, and 28.9%, respectively. Information about statistical significance was not provided in the poster.
Dr. Levy said he would “expect most NMO patients to initially be diagnosed with MS. It’s unusual to start with a diagnosis of NMO and then figure out it’s MS.”
As for the larger number of people with interchangeable diagnoses, Dr. Levy said that likely “reflects the messiness of billing codes.” For his part, Mr. Wong said there could be multiple causes for the interchangeable diagnoses: lack of disease knowledge, miscoding, lack of Food and Drug Administration–approved treatment for NMO at the time, and potentially other factors.
What does it all mean?
As for the study’s significance, Mr. Wong said a full workup should be performed before diagnosis, “and a neurologist should never prescribe disease-modifying therapies prior to a confirmation of diagnosis.”
Indeed, some disease-modifying therapies for MS are inappropriate for patients with NMO, Dr. Levy said. “The older medications, including beta-interferons, are among the most harmful to NMO patients. But they are not commonly used as first line for MS as they used to be. In contrast, B cell–depleting medications like ocrelizumab may be helpful in NMO.”
In regards to diagnosis, Dr. Levy noted that the NMO aquaporin-4 (AQP4) antibody test is “extremely specific and reliable.”
“A positive test result in the context of a clinical presentation of central nervous system inflammation allows for the diagnosis of NMO,” he said. “A negative test result is more complicated and may require some expertise to sort out after a careful review of the history, neurological exam, MRI features, central nervous system testing and other blood test results.”
The study was funded by the Sumaira Foundation. The authors did not provide information about relevant disclosures. Dr. Levy reports personal compensation for advisory board activities from Roche, Genentech, Chugai, Horizon, Alexion and Mitsubishi and grant support from Genentech, Horizon, Alexion, Sanofi, and UCB.
MILAN – , according to a poster presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
“There is a lack of education in differentiating between MS and NMO even in the medical community, which may result in a high misdiagnosis rate,” said study lead author Ka-Ho Wong, MBA, of the University of Utah, Salt Lake City, in an interview.
“NMO was recognized in the late 1800s and was historically thought to be a variant of MS until 1999,” said Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, both in Boston, in an interview.
“They are both relapsing inflammatory disorders of the central nervous system with similarities in symptoms of weakness, numbness, mobility problem, vision defects, pain and fatigue,” said Dr. Levy, who did not take part in the new study. “A blood test for NMO was developed in 2004 and improved over time to the point that it can now reliably distinguish NMO from MS.”
As for therapy, “recent research has confirmed the two conditions are immunologically different and respond to different treatment,” Dr. Levy said. “The treatments developed for MS, especially from the 1990s, are harmful in NMO so it is important to make the diagnosis correctly.”
He added that “we do not recognize overlap between NMO or MS – it’s one or the other.”
Exploring the reasons for misdiagnosis
Mr. Wong, the present study’s lead author, said he and a research team launched the new study to better understand who gets misdiagnosed. “We know that almost 50% of the individuals get misdiagnosed at some point. However, what we don’t know yet is if the influencing factors are social determinants of health or if there are other causes.”
For the study, Mr. Wong and colleagues analyzed data from TriNetX, a health research network with access to medical records from 61 U.S. health care organizations. providing access to electronic medical records that includes sixty-one health care organizations (HCOs) in the United States.
ICD-10 coding statistics from 2008 to 2022 identified 7,657 patients with diagnoses for NMO. Of those, 4,040 (53%) only had diagnoses for NMO, and the rest (3,617, 47%) had diagnoses for both NMO and MS.
The researchers focused on 1,265 patients who had been coded for both diagnoses and had at least three clinical visits. They determined that a patient was misdiagnosed when they had three consecutive diagnoses of the same type. “For example, if they had MS but got misdiagnosed as NMO, once they are confirmed as MS they must have three or more consecutive diagnosis of MS to be considered as misdiagnosed,” Mr. Wong said.
Of the 1,265 subjects, the researchers determined that 308 (24%) had NMO but had been misdiagnosed as having MS, 189 (15%) had MS but were misdiagnosed as having NMO, and 768 (61%) were interchangeably diagnosed with the two conditions over time.
Among these three groups, 70.8%, 73.1%, and 78.4% were female, respectively; and 59.4%, 52.9%, and 53.0% were White, respectively. The percentages of Black patients were 17.2%, 24.3%, and 28.9%, respectively. Information about statistical significance was not provided in the poster.
Dr. Levy said he would “expect most NMO patients to initially be diagnosed with MS. It’s unusual to start with a diagnosis of NMO and then figure out it’s MS.”
As for the larger number of people with interchangeable diagnoses, Dr. Levy said that likely “reflects the messiness of billing codes.” For his part, Mr. Wong said there could be multiple causes for the interchangeable diagnoses: lack of disease knowledge, miscoding, lack of Food and Drug Administration–approved treatment for NMO at the time, and potentially other factors.
What does it all mean?
As for the study’s significance, Mr. Wong said a full workup should be performed before diagnosis, “and a neurologist should never prescribe disease-modifying therapies prior to a confirmation of diagnosis.”
Indeed, some disease-modifying therapies for MS are inappropriate for patients with NMO, Dr. Levy said. “The older medications, including beta-interferons, are among the most harmful to NMO patients. But they are not commonly used as first line for MS as they used to be. In contrast, B cell–depleting medications like ocrelizumab may be helpful in NMO.”
In regards to diagnosis, Dr. Levy noted that the NMO aquaporin-4 (AQP4) antibody test is “extremely specific and reliable.”
“A positive test result in the context of a clinical presentation of central nervous system inflammation allows for the diagnosis of NMO,” he said. “A negative test result is more complicated and may require some expertise to sort out after a careful review of the history, neurological exam, MRI features, central nervous system testing and other blood test results.”
The study was funded by the Sumaira Foundation. The authors did not provide information about relevant disclosures. Dr. Levy reports personal compensation for advisory board activities from Roche, Genentech, Chugai, Horizon, Alexion and Mitsubishi and grant support from Genentech, Horizon, Alexion, Sanofi, and UCB.
MILAN – , according to a poster presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
“There is a lack of education in differentiating between MS and NMO even in the medical community, which may result in a high misdiagnosis rate,” said study lead author Ka-Ho Wong, MBA, of the University of Utah, Salt Lake City, in an interview.
“NMO was recognized in the late 1800s and was historically thought to be a variant of MS until 1999,” said Michael Levy, MD, PhD, of Harvard Medical School and Massachusetts General Hospital, both in Boston, in an interview.
“They are both relapsing inflammatory disorders of the central nervous system with similarities in symptoms of weakness, numbness, mobility problem, vision defects, pain and fatigue,” said Dr. Levy, who did not take part in the new study. “A blood test for NMO was developed in 2004 and improved over time to the point that it can now reliably distinguish NMO from MS.”
As for therapy, “recent research has confirmed the two conditions are immunologically different and respond to different treatment,” Dr. Levy said. “The treatments developed for MS, especially from the 1990s, are harmful in NMO so it is important to make the diagnosis correctly.”
He added that “we do not recognize overlap between NMO or MS – it’s one or the other.”
Exploring the reasons for misdiagnosis
Mr. Wong, the present study’s lead author, said he and a research team launched the new study to better understand who gets misdiagnosed. “We know that almost 50% of the individuals get misdiagnosed at some point. However, what we don’t know yet is if the influencing factors are social determinants of health or if there are other causes.”
For the study, Mr. Wong and colleagues analyzed data from TriNetX, a health research network with access to medical records from 61 U.S. health care organizations. providing access to electronic medical records that includes sixty-one health care organizations (HCOs) in the United States.
ICD-10 coding statistics from 2008 to 2022 identified 7,657 patients with diagnoses for NMO. Of those, 4,040 (53%) only had diagnoses for NMO, and the rest (3,617, 47%) had diagnoses for both NMO and MS.
The researchers focused on 1,265 patients who had been coded for both diagnoses and had at least three clinical visits. They determined that a patient was misdiagnosed when they had three consecutive diagnoses of the same type. “For example, if they had MS but got misdiagnosed as NMO, once they are confirmed as MS they must have three or more consecutive diagnosis of MS to be considered as misdiagnosed,” Mr. Wong said.
Of the 1,265 subjects, the researchers determined that 308 (24%) had NMO but had been misdiagnosed as having MS, 189 (15%) had MS but were misdiagnosed as having NMO, and 768 (61%) were interchangeably diagnosed with the two conditions over time.
Among these three groups, 70.8%, 73.1%, and 78.4% were female, respectively; and 59.4%, 52.9%, and 53.0% were White, respectively. The percentages of Black patients were 17.2%, 24.3%, and 28.9%, respectively. Information about statistical significance was not provided in the poster.
Dr. Levy said he would “expect most NMO patients to initially be diagnosed with MS. It’s unusual to start with a diagnosis of NMO and then figure out it’s MS.”
As for the larger number of people with interchangeable diagnoses, Dr. Levy said that likely “reflects the messiness of billing codes.” For his part, Mr. Wong said there could be multiple causes for the interchangeable diagnoses: lack of disease knowledge, miscoding, lack of Food and Drug Administration–approved treatment for NMO at the time, and potentially other factors.
What does it all mean?
As for the study’s significance, Mr. Wong said a full workup should be performed before diagnosis, “and a neurologist should never prescribe disease-modifying therapies prior to a confirmation of diagnosis.”
Indeed, some disease-modifying therapies for MS are inappropriate for patients with NMO, Dr. Levy said. “The older medications, including beta-interferons, are among the most harmful to NMO patients. But they are not commonly used as first line for MS as they used to be. In contrast, B cell–depleting medications like ocrelizumab may be helpful in NMO.”
In regards to diagnosis, Dr. Levy noted that the NMO aquaporin-4 (AQP4) antibody test is “extremely specific and reliable.”
“A positive test result in the context of a clinical presentation of central nervous system inflammation allows for the diagnosis of NMO,” he said. “A negative test result is more complicated and may require some expertise to sort out after a careful review of the history, neurological exam, MRI features, central nervous system testing and other blood test results.”
The study was funded by the Sumaira Foundation. The authors did not provide information about relevant disclosures. Dr. Levy reports personal compensation for advisory board activities from Roche, Genentech, Chugai, Horizon, Alexion and Mitsubishi and grant support from Genentech, Horizon, Alexion, Sanofi, and UCB.
AT ECTRIMS 2023
EBV and MS: Just how deep is the link?
MILAN – in a joint presentation at the 9th Joint ECTRIMS-ACTRIMS meeting.
Armed with the findings of his own landmark 2022 study into EBV and MS, Harvard Medical School, Boston, professor of medicine Alberto Ascherio, MD, DrPH, argued that they’re tightly connected. But rheumatologist William H. Robinson, MD, PhD, of Stanford (Calif.) University, said that while he also believes EBV plays a significant role in MS, “there’s likely a role for a second hit” – some other factor. “Why are 95% of us EBV-infected, but only a small subset ultimately develop MS or ... other autoimmune diseases?”
As a 2023 review noted, researchers have puzzled over the connection between EBV and MS since the early 1980s. “Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS.” But it’s not clear how EBV – which strikes more than an estimated 95% of humans and causes mononucleosis – manages to trigger MS.
A rare complication of EBV infection
In the 2022 study, Dr. Ascherio aimed to understand exactly how deeply EBV and MS are connected by analyzing serum data gathered from more than 10 million active-duty members of the U.S. military. Of those, 955 were diagnosed with MS.
The researchers focused on 801 subjects with MS and matched them to 1,566 controls. Only 1 of the 801 subjects with MS had a negative EBV test prior to diagnosis, a fact that researchers believe could be due to a factor such as a failure to seroconvert during infection. “At baseline, 35 MS cases and 107 controls were EBV-negative,” the study reported. “All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up.”
Overall, subjects who were positive for EBV were 32.4 times to develop MS than those who weren’t (95% confidence interval, 4.3-245.3; P < 0.001).
Is it possible that immune dysregulation from MS precedes EBV infection? The researchers analyzed viruses in 30 subjects with MS – before and after MS onset – and in 30 controls. The findings suggested that EBV was the major player, Dr. Ascherio said.
Researchers also focused on cytomegalovirus (CMV) infection, which is closely related to EBV and to the chicken pox virus. “CMV seroconversion is not associated with MS, and positivity for CMV at baseline was associated with a modestly lower risk of MS,” Dr. Ascherio said.
In the big picture, “this data establishes beyond reasonable doubt that MS is a rare complication of EBV infection,” Dr. Ascherio said. “The main question now is whether the virus triggers an immune process that then is self-maintained, or whether the presence of the infection keeps feeding the immune process.”
Inadequate evidence for causation
In his presentation, Dr. Robinson asked: “Does EBV cause MS? Really? All of MS? In humans [with MS], yes, we found monoclonal antibodies expressed by the B cells that bound to EBV. But we also found spinal fluid B cells and coding antibodies that bound to multiple other viruses, including rubella, VZV [varicella-zoster virus/chickenpox], CMV, and HSV [herpes simplex virus]. And there’s even a measles reactive antibody there.”
And there’s evidence that human herpes virus type 6 (HHV-6) and HHV-6A could be linked to MS: “Maybe HHV-6 or HHV-6A is the cause of MS in a subset of patients,” Dr. Robinson said. Research suggests that pox viruses could be another possible cause, he said.
He added: “I’m a rheumatologist, and I see patients in the clinic and in the hospital who have lupus, a disease highly associated with EBV infection. But they definitely do not have MS, nor do they have RA [rheumatoid arthritis], and likewise your MS patients don’t have lupus. What’s up with all these diseases potentially being linked to EBV?”
A missing piece of the puzzle?
In a discussion period, Dr. Ascherio responded to Dr. Robinson by saying he’s waiting to see evidence that patients with the other diseases linked to EBV don’t develop them if they’re EBV-negative. Dr. Ascherio added that it’s possible that there are different strains of EBV, and some may be more likely to cause MS.
What does this all mean for MS prevention? In a commentary published with Dr. Ascherio’s 2022 study, Dr. Robinson and a coauthor asked: “Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease? Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”
Dr. Ascherio discloses speaker/consultant relationships with Prada Foundation, WebMD, Biogen, Moderna, Merck, Roche, and GSK. Dr. Robinson discloses unspecified relationships with Altreca and Flatiron Bio, and he is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV.
MILAN – in a joint presentation at the 9th Joint ECTRIMS-ACTRIMS meeting.
Armed with the findings of his own landmark 2022 study into EBV and MS, Harvard Medical School, Boston, professor of medicine Alberto Ascherio, MD, DrPH, argued that they’re tightly connected. But rheumatologist William H. Robinson, MD, PhD, of Stanford (Calif.) University, said that while he also believes EBV plays a significant role in MS, “there’s likely a role for a second hit” – some other factor. “Why are 95% of us EBV-infected, but only a small subset ultimately develop MS or ... other autoimmune diseases?”
As a 2023 review noted, researchers have puzzled over the connection between EBV and MS since the early 1980s. “Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS.” But it’s not clear how EBV – which strikes more than an estimated 95% of humans and causes mononucleosis – manages to trigger MS.
A rare complication of EBV infection
In the 2022 study, Dr. Ascherio aimed to understand exactly how deeply EBV and MS are connected by analyzing serum data gathered from more than 10 million active-duty members of the U.S. military. Of those, 955 were diagnosed with MS.
The researchers focused on 801 subjects with MS and matched them to 1,566 controls. Only 1 of the 801 subjects with MS had a negative EBV test prior to diagnosis, a fact that researchers believe could be due to a factor such as a failure to seroconvert during infection. “At baseline, 35 MS cases and 107 controls were EBV-negative,” the study reported. “All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up.”
Overall, subjects who were positive for EBV were 32.4 times to develop MS than those who weren’t (95% confidence interval, 4.3-245.3; P < 0.001).
Is it possible that immune dysregulation from MS precedes EBV infection? The researchers analyzed viruses in 30 subjects with MS – before and after MS onset – and in 30 controls. The findings suggested that EBV was the major player, Dr. Ascherio said.
Researchers also focused on cytomegalovirus (CMV) infection, which is closely related to EBV and to the chicken pox virus. “CMV seroconversion is not associated with MS, and positivity for CMV at baseline was associated with a modestly lower risk of MS,” Dr. Ascherio said.
In the big picture, “this data establishes beyond reasonable doubt that MS is a rare complication of EBV infection,” Dr. Ascherio said. “The main question now is whether the virus triggers an immune process that then is self-maintained, or whether the presence of the infection keeps feeding the immune process.”
Inadequate evidence for causation
In his presentation, Dr. Robinson asked: “Does EBV cause MS? Really? All of MS? In humans [with MS], yes, we found monoclonal antibodies expressed by the B cells that bound to EBV. But we also found spinal fluid B cells and coding antibodies that bound to multiple other viruses, including rubella, VZV [varicella-zoster virus/chickenpox], CMV, and HSV [herpes simplex virus]. And there’s even a measles reactive antibody there.”
And there’s evidence that human herpes virus type 6 (HHV-6) and HHV-6A could be linked to MS: “Maybe HHV-6 or HHV-6A is the cause of MS in a subset of patients,” Dr. Robinson said. Research suggests that pox viruses could be another possible cause, he said.
He added: “I’m a rheumatologist, and I see patients in the clinic and in the hospital who have lupus, a disease highly associated with EBV infection. But they definitely do not have MS, nor do they have RA [rheumatoid arthritis], and likewise your MS patients don’t have lupus. What’s up with all these diseases potentially being linked to EBV?”
A missing piece of the puzzle?
In a discussion period, Dr. Ascherio responded to Dr. Robinson by saying he’s waiting to see evidence that patients with the other diseases linked to EBV don’t develop them if they’re EBV-negative. Dr. Ascherio added that it’s possible that there are different strains of EBV, and some may be more likely to cause MS.
What does this all mean for MS prevention? In a commentary published with Dr. Ascherio’s 2022 study, Dr. Robinson and a coauthor asked: “Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease? Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”
Dr. Ascherio discloses speaker/consultant relationships with Prada Foundation, WebMD, Biogen, Moderna, Merck, Roche, and GSK. Dr. Robinson discloses unspecified relationships with Altreca and Flatiron Bio, and he is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV.
MILAN – in a joint presentation at the 9th Joint ECTRIMS-ACTRIMS meeting.
Armed with the findings of his own landmark 2022 study into EBV and MS, Harvard Medical School, Boston, professor of medicine Alberto Ascherio, MD, DrPH, argued that they’re tightly connected. But rheumatologist William H. Robinson, MD, PhD, of Stanford (Calif.) University, said that while he also believes EBV plays a significant role in MS, “there’s likely a role for a second hit” – some other factor. “Why are 95% of us EBV-infected, but only a small subset ultimately develop MS or ... other autoimmune diseases?”
As a 2023 review noted, researchers have puzzled over the connection between EBV and MS since the early 1980s. “Until that point, EBV was primarily viewed as a cancer-causing agent, but the culmination of evidence now shows that EBV has a pivotal role in development of MS.” But it’s not clear how EBV – which strikes more than an estimated 95% of humans and causes mononucleosis – manages to trigger MS.
A rare complication of EBV infection
In the 2022 study, Dr. Ascherio aimed to understand exactly how deeply EBV and MS are connected by analyzing serum data gathered from more than 10 million active-duty members of the U.S. military. Of those, 955 were diagnosed with MS.
The researchers focused on 801 subjects with MS and matched them to 1,566 controls. Only 1 of the 801 subjects with MS had a negative EBV test prior to diagnosis, a fact that researchers believe could be due to a factor such as a failure to seroconvert during infection. “At baseline, 35 MS cases and 107 controls were EBV-negative,” the study reported. “All but one of these 35 EBV-negative MS cases became infected with EBV during the follow-up.”
Overall, subjects who were positive for EBV were 32.4 times to develop MS than those who weren’t (95% confidence interval, 4.3-245.3; P < 0.001).
Is it possible that immune dysregulation from MS precedes EBV infection? The researchers analyzed viruses in 30 subjects with MS – before and after MS onset – and in 30 controls. The findings suggested that EBV was the major player, Dr. Ascherio said.
Researchers also focused on cytomegalovirus (CMV) infection, which is closely related to EBV and to the chicken pox virus. “CMV seroconversion is not associated with MS, and positivity for CMV at baseline was associated with a modestly lower risk of MS,” Dr. Ascherio said.
In the big picture, “this data establishes beyond reasonable doubt that MS is a rare complication of EBV infection,” Dr. Ascherio said. “The main question now is whether the virus triggers an immune process that then is self-maintained, or whether the presence of the infection keeps feeding the immune process.”
Inadequate evidence for causation
In his presentation, Dr. Robinson asked: “Does EBV cause MS? Really? All of MS? In humans [with MS], yes, we found monoclonal antibodies expressed by the B cells that bound to EBV. But we also found spinal fluid B cells and coding antibodies that bound to multiple other viruses, including rubella, VZV [varicella-zoster virus/chickenpox], CMV, and HSV [herpes simplex virus]. And there’s even a measles reactive antibody there.”
And there’s evidence that human herpes virus type 6 (HHV-6) and HHV-6A could be linked to MS: “Maybe HHV-6 or HHV-6A is the cause of MS in a subset of patients,” Dr. Robinson said. Research suggests that pox viruses could be another possible cause, he said.
He added: “I’m a rheumatologist, and I see patients in the clinic and in the hospital who have lupus, a disease highly associated with EBV infection. But they definitely do not have MS, nor do they have RA [rheumatoid arthritis], and likewise your MS patients don’t have lupus. What’s up with all these diseases potentially being linked to EBV?”
A missing piece of the puzzle?
In a discussion period, Dr. Ascherio responded to Dr. Robinson by saying he’s waiting to see evidence that patients with the other diseases linked to EBV don’t develop them if they’re EBV-negative. Dr. Ascherio added that it’s possible that there are different strains of EBV, and some may be more likely to cause MS.
What does this all mean for MS prevention? In a commentary published with Dr. Ascherio’s 2022 study, Dr. Robinson and a coauthor asked: “Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease? Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”
Dr. Ascherio discloses speaker/consultant relationships with Prada Foundation, WebMD, Biogen, Moderna, Merck, Roche, and GSK. Dr. Robinson discloses unspecified relationships with Altreca and Flatiron Bio, and he is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV.
AT ECTRIMS 2023
Stem cell transplants in early MS: Who benefits most?
MILAN – researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.
“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).
However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”
Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”
But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”
Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.
However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”
Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.
The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.
The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.
What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”
He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”
Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”
Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.
MILAN – researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.
“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).
However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”
Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”
But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”
Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.
However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”
Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.
The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.
The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.
What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”
He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”
Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”
Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.
MILAN – researchers told colleagues at the 9th Joint ECTRIMS-ACTRIMS meeting. But there’s no consensus over best practices.
“Is this a good alternative regarding treatment efficacy and risk? When should we switch from standard treatment? Should we switch from a low-efficacy treatment, from a previous high-efficacy treatment, or from two or more? There is no agreement on this at the moment,” said neurologist Lars Bø, MD, PhD, a professor at the University of Bergen (Norway).
However, rapid conversion to efficient treatment in the early stages of disease is turning out to be crucial, Dr. Bø said. “Early inflammatory activity has lasting effects. A delay from less than 2 years to 4-6 years has implications for disability.”
Where does HSCT fit in? According to Dr. Bø, a 2017 study found that newer treatments bring up to 50% of patients to no evidence of disease activity at 2 years compared with 70%-90% for HSCT. That study reported that “optimal candidates ... are young, ambulatory, and have inflammatory-active relapsing remitting MS.”
But other research is presenting a different picture with “data that doesn’t show such a clear-cut difference.” Dr. Bø highlighted a study published earlier this year that found that HSCT was “considerably superior” to fingolimod and “marginally superior” to natalizumab, but was not superior to ocrelizumab over shorter periods of time. As a result, “there is a need for further randomized trials comparing [HSCT] with these newer medications.”
Would it make sense to treat all younger patients with highly active MS? Research does suggest that “there’s a significant benefit in what we describe as aggressive [disease], high-disability, young age, very short disease lengths,” said neurologist Richard Nicholas, MBBS, of Imperial College London, in a separate presentation.
However, he cautioned that not everyone with highly active MS may be appropriate for HSCT. “That number could be as high as 15%, and “that’s a rather large group of people who would be treated with this therapy.” He suggested focusing on “the most important features”: “two or more relapses and also rapid accrual of disabilities.”
Dr. Nicholas also noted the findings of a study that he coauthored into HSCT versus alemtuzumab and ocrelizumab. The findings of that study were released at ECTRIMS and presented by neurologist Antonio Scalfari, MD, PhD, of Imperial College Healthcare NHS Trust.
The researchers tracked 103 patients after stem cell transplants (median, 45 months), 204 patients on alemtuzumab (median, 45 months), and 314 patients on ocrelizumab (median, 35 months). Those who received transplants had a 74% lower risk of relapse versus alemtuzumab, and a 66% lower risk of new MS activity detected via MRI. Compared with ocrelizumab, patients who received stem cell transplants had a 60% lower risk of relapse but the same risk of MS activity detected via MRI.
The researchers noted that the patients who underwent stem cell transplantation had numerous adverse effects.
What happens now? “HSCT should be available for our MS patients when standard treatment is no longer effective,” Dr. Bø said. “When treatment options are limited, it is likely to have a good effect in younger patients with a shorter disease duration and a low disability.”
He added that “there is an increasing use of high-efficacy treatment early in RRMS [relapsing-remitting MS], and this may make the subgroup with indication for HSCT as a rescue therapy smaller.”
Meanwhile, he said, “demonstrating a higher efficacy may require larger studies and a combined analysis of data from the ongoing randomized trials. Also, there is a need for follow-up longer than 2 or 3 years for the estimation of cost versus benefit for this treatment.”
Dr. Bø disclosed receiving speaker fees from Novartis and consulting fees from Viatris. Dr. Nicholas disclosed speaker advisory board relationships with Roche and Novartis.
AT ECTRIMS 2023