Multiple Sclerosis

SAN DIEGO – Weight loss from intermittently cutting calories has a positive effect on cognitive, immunologic, and other outcomes for patients with multiple sclerosis (MS), new research suggests.

Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.

Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

High adherence rate

Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.

The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.

Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.

In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.

Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.

Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.

Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.

“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
 

Maintain healthy weight

The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.

There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.

Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.

However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.

She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
 

Superb study

Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.

“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.

Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.

The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – Weight loss from intermittently cutting calories has a positive effect on cognitive, immunologic, and other outcomes for patients with multiple sclerosis (MS), new research suggests.

Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.

Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

High adherence rate

Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.

The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.

Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.

In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.

Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.

Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.

Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.

“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
 

Maintain healthy weight

The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.

There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.

Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.

However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.

She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
 

Superb study

Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.

“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.

Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.

The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – Weight loss from intermittently cutting calories has a positive effect on cognitive, immunologic, and other outcomes for patients with multiple sclerosis (MS), new research suggests.

Although this was just one small 12-week trial, “we were still able to see an amelioration in certain measures, for example, measures of fatigue as well as measures of cognitive function” in participants following the diet, said study investigator Laura Piccio, MD, PhD, associate professor, Washington University, St. Louis, and the University of Sydney.

Overall, the results underscore the importance of patients with MS maintaining an ideal body weight, Dr. Piccio said.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

High adherence rate

Obesity, which is associated with increased inflammation, has previously been linked to the development of MS. Release of adipokines from adipose tissue “shifts the balance” toward a proinflammatory milieu; and a chronic low-grade inflammatory state may promote autoimmunity, Dr. Piccio noted.

The current study included 42 adult patients (85.7% women; mean age, 48.2 years) with relapsing-remitting MS. Their mean baseline body mass index was 28.7, indicating being overweight, and the mean weight was 80.7 kg. The median Expanded Disability Status Scale (EDSS) score was 2.0.

Researchers randomly assigned participants to an intermittent calorie restriction (iCR) group or to a control group. For 2 days per week, the diet group ate 25% of what they normally would. For example, they might consume 500 calories from salads and non-starchy vegetables with a light dressing, Dr. Piccio said. The control group was not restricted in their eating.

In addition to the baseline assessment, the patients had study visits at weeks 6 and 12. Researchers adjusted for age, sex, and use of MS disease-modifying therapy.

Calorie reduction turned out to be a feasible intervention. “We had a pretty high adherence to the diet,” with 17 members of each group completing the study, Dr. Piccio reported. “So it shows this diet is possible,” she added.

Participants in the iCR group demonstrated a significant decrease in weight, BMI, and waist circumference at weeks 6 and 12 compared with baseline. They lost an average of 2.2 kg (about 5 pounds) over the course of the trial.

Serum leptin levels were also significantly decreased in the iCR group – and several lipids affected by the diet were positively correlated with adiponectin. Calorie restriction also affected T-cell subtypes.

“We definitely had an impact on body weight and also changes in certain inflammatory markers,” said Dr. Piccio.
 

Maintain healthy weight

The diet affected clinical measures, too. The score on the Symbol Digit Modalities Test (SDMT) increased significantly with iCR at 6 weeks (mean increase, 3.5; 95% confidence interval [CI], 0.6-6.3; P = .01) and 12 weeks (mean increase, 6.2; 95% CI, 3.4–9.5; P = .00004) compared with baseline.

There were no significant differences on the SDMT in the control group over time. In addition, the mean score on this test at 12 weeks was significantly higher in the iCR group compared with the control group.

Researchers also noted benefits of the diet on some patient-reported outcomes, such as certain subscales of the Modified Fatigue Impact Scale.

However, Dr. Piccio stressed that these results should be viewed with caution. “There could be many other factors driving this change in a small study like this,” she said. For example, just being on a diet might make individuals feel and function better. Dr. Piccio added that it is not clear what happens when participants return to their normal diet and their original body weight.

She noted that it is probably important to “get to a healthy body weight and to maintain it” – and it may not matter whether that’s through intermittent fasting or changing diet in other ways. “Anything you can do in order to keep your body weight within a normal range is important,” Dr. Piccio said.
 

Superb study

Commenting on the study findings, ACTRIMS program committee chair Catherine Larochelle, MD, PhD, clinician-scientist at Centre Hospitalier de l’Université de Montréal, said results from this “superb” study suggest that cognition can be positively influenced by healthy dietary habits.

“This is very promising and exciting,” Dr. Larochelle said. However, she cautioned that the data need to be reproduced and confirmed in other cohorts.

Overall, Dr. Larochelle noted that diet is becoming a “hot topic” in the field of MS. “This effervescent field of research should lead to new nonpharmacological therapeutic approaches to complement existing disease-modifying therapies and improve meaningful outcomes for people with MS,” she said.

The study was funded by the National MS Society in the United States. Dr. Piccio and Dr. Larochelle have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – The prevalence of psychiatric morbidity is significantly higher among patients with multiple sclerosis (MS) versus controls in each of the 5 years prior to the onset of the disease, new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.

These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.

With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Psychiatric morbidity during the prodromal phase of MS

Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.

Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.

The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.

The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.

The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.

The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.

Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.

It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.

In addition to psychiatric complaints, MS patients experience other symptoms, including  pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.

Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.

He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
 

When does MS start?

Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.

He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”

Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.

The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – The prevalence of psychiatric morbidity is significantly higher among patients with multiple sclerosis (MS) versus controls in each of the 5 years prior to the onset of the disease, new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.

These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.

With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Psychiatric morbidity during the prodromal phase of MS

Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.

Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.

The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.

The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.

The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.

The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.

Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.

It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.

In addition to psychiatric complaints, MS patients experience other symptoms, including  pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.

Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.

He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
 

When does MS start?

Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.

He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”

Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.

The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – The prevalence of psychiatric morbidity is significantly higher among patients with multiple sclerosis (MS) versus controls in each of the 5 years prior to the onset of the disease, new research reveals. Results of a population-based study show the relative risk of psychiatric morbidity, including depression and anxiety, was up to 88% higher in patients with MS, compared with their counterparts without the disease.

These results are an incentive to “keep exploring” to get a “clearer picture” of the MS prodrome, said study investigator Anibal Chertcoff, MD, who is trained both as a neurologist and psychiatrist and is a postdoctoral fellow at the University of British Columbia, Vancouver.

With a better understanding of this phase, it might be possible to “push the limits to get an earlier diagnosis of MS,” said Dr. Chertcoff.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Psychiatric morbidity during the prodromal phase of MS

Psychiatric comorbidities are common in MS. Emerging research suggests psychiatric disorders may be present before disease onset.

Using administrative and clinical data, the investigators collected information on MS cases and healthy matched controls who had no demyelinating disease claims. They used a clinical cohort of patients attending an MS clinic and a much larger administrative cohort that used an algorithm to detect MS cases using diagnostic codes and prescription data for disease modifying therapies.

The administrative cohort consisted of 6,863 MS cases and 31,865 controls while the clinical cohort had 966 cases and 4,534 controls. The majority (73%) of cases and controls were female. The mean age at the first demyelinating claim was 44 years.

The study’s primary outcome was prevalence of psychiatric morbidity using diagnostic codes for depression, anxiety, bipolar disorder, and schizophrenia. In the 5 years pre-MS onset, 28% of MS cases and 14.9% of controls had psychiatric morbidity.

The researchers plotted psychiatric morbidity in both MS cases and controls over time on a graph. “In terms of the prevalence of psychiatric morbidity, in each year the difference between the groups, at least visually, seems to increase with time as it gets closer to MS onset,” said Dr. Chertcoff.

The analysis showed the relative risk of psychiatric morbidity over the 5 years before MS onset was 1.88 (95% confidence interval, 1.80-1.97) in the administrative cohort, and 1.57 (95% CI, 1.36-1.80) in the clinical cohort.

Secondary analyses showed individuals with MS had more yearly physician visits, visits to psychiatrists, psychiatric hospital admissions, and prescription fills for psychiatric medication, compared with controls. This, said Dr. Chertcoff, illustrates the burden psychiatric morbidity during the prodromal phase of MS places on health care resources.

It’s possible that low-grade inflammation, which is linked to MS, is also pushing these psychiatric phenomena, said Dr. Chertcoff. He noted that the prevalence of depression is significantly higher not only in MS, but in a wide range of other inflammatory conditions.

In addition to psychiatric complaints, MS patients experience other symptoms, including  pain, sleep disturbances, fatigue, and gastrointestinal issues during the MS prodrome, said Dr. Chertcoff.

Patients with MS are often seeing other physicians – including psychiatrists during the prodromal phase of the disease. Neurologists, Dr. Chertcoff said, could perhaps “raise awareness” among these other specialists about the prevalence of psychiatric morbidities during this phase.

He hopes experts in the field will consider developing research criteria for the MS prodrome similar to what has been done in Parkinson’s disease.
 

When does MS start?

Commenting on the research findings, Mark Freedman, MD, professor of medicine (Neurology), University of Ottawa, and director of the multiple sclerosis research unit, Ottawa Hospital-General Campus, said the study illustrates the increased research attention the interplay between MS and psychiatric disorders is getting.

He recalled “one of the most compelling” recent studies that looked at a large group of children with MS and showed their grades started falling more than 5 years before developing MS symptoms. “You could see their grades going down year by year by year, so an indicator that a young brain, which should be like a sponge and improving, was actually faltering well before the symptoms.”

Results from this new study continue to beg the question of when MS actually starts, said Dr. Freedman.

The study received funding from the U.S. National MS Society, the MS Society of Canada, and the Michael Smith Foundation. Dr. Chertcoff and Dr. Freedman reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

SAN DIEGO – A new retrospective analysis of patients with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) indicates that treatment with immunotherapy is associated with a lower risk of relapse. The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.

MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Predicting which patients will relapse

“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.

The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).

However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
 

The most effective treatment for relapsing MOGAD

In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.

Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.

Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.

He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.

“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
 

‘A good beginning’

The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.

“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.

Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.

SAN DIEGO – A new retrospective analysis of patients with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) indicates that treatment with immunotherapy is associated with a lower risk of relapse. The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.

MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Predicting which patients will relapse

“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.

The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).

However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
 

The most effective treatment for relapsing MOGAD

In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.

Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.

Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.

He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.

“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
 

‘A good beginning’

The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.

“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.

Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.

SAN DIEGO – A new retrospective analysis of patients with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) indicates that treatment with immunotherapy is associated with a lower risk of relapse. The authors note that many MOGAD patients never experience a relapse and it is difficult to predict which ones will.

MOGAD can cause optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis (ADEM). It was first described in 2007, and the best approaches to therapy are not yet understood. The new study is at least a starting point for understanding treatment outcomes, according to Philippe Bilodeau, MD, who presented the study during a poster session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Predicting which patients will relapse

“I think one of the biggest unanswered clinical questions in MOGAD is trying to determine who’s going to go on to have relapsing MOGAD. About 30% to 40% of patients with MOGAD will never have a second attack. So one of the big questions is: How can we identify patients who would benefit from immunotherapy, and how can we identify patients who will have a more benign disease course and may not need to be started on a treatment,” said Dr. Bilodeau, a neurology resident at Massachusetts General Hospital/Brigham and Women’s Hospital, Boston.

The researchers analyzed data from 143 patients seen at Massachusetts General or Brigham and Women’s Hospital who had presented with their first attack. Over a follow-up period of 5 years, the relapse rate was 61.8%. The researchers examined various factors, including age of onset, high MOG titer, attack type, and male sex, and found that only the latter came close to predicting relapse, though it fell short of clinical significance (hazard ratio [HR], 0.61; P = .07).

However, treatment with mycophenolate, azathioprine, intravenous immunoglobulins (IVIG), rituximab, or tocilizumab strongly predicted a lower probability of relapse (HR, 0.25; P < .0001).
 

The most effective treatment for relapsing MOGAD

In a separate poster, his team examined a subset of the cohort of 88 patients who were treated with mycophenolate mofetil, B-cell depletion, rituximab, or IV immunoglobulins (IVIG) during a first or second relapse, as well as an analysis of every relapse experienced by any patient during the course of their disease. “Using a negative binomial regression, we looked at the annualized relapse rates and incidence rate ratios between the different treatments. No matter how you looked at the data – even if you looked at total time on IVIG, if you looked at time on monotherapy, excluding if they were on prednisone at the same time if they were on both IVIG and rituximab, if you only consider patients that were on high dose IVIG – IVIG was by far the best treatment and rituximab was always the least effective, and mycophenolate was always between IVIG and rituximab. So I think in that cohort, we can say with some confidence that IVIG is the most effective treatment for relapsing MOGAD,” said Dr. Bilodeau.

Other studies had suggested efficacy of individual treatments, but “I think what hadn’t been done is taking one cohort and comparing those treatments head to head, so that’s what we were trying to do,” said Dr. Bilodeau.

Both studies have the usual caveats of a retrospective study and so cannot prove causality. “We need to find more covariates to make sure that there’s no confounding (factor) explaining this and to make sure that there aren’t other demographic or clinical factors that explain the association. But as it stands, I think at this time starting treatment with immunotherapy is the only thing that we know will reduce the risk of having a future relapse. There’s a lot of further analysis that we need to do,” said Dr. Bilodeau.

He said that the study also provided some preliminary insight into treatment of pediatric disease. “We have interesting data from that analysis that pediatric-onset MOGAD actually had a particularly good response to [mycophenolate], more so than in adults,” he said.

“At this point, I think a rational approach if you have someone coming in with a first relapse is, you have to assess their risk tolerance. If they’re a very risk-averse patient, I think it’s reasonable to start them on treatment. I think it’s reasonable to monitor their titer. There’s some data that if they seroconvert to negative, you might be able to stop immunotherapy. If someone has established relapsing disease, and they have adult onset [disease], IVIG should be the first-line treatment. If they’re pediatric onset, either [mycophenolate] or IVIG are probably good first line treatments,” he said.
 

‘A good beginning’

The studies are a good beginning to getting a better understanding of MOGAD treatment, according to Michael Cossoy, MD, who attended the poster session and was asked to comment on the study.

“It’s interesting because MOG antibody-associated disease is so relatively new that we don’t have a great idea yet about who needs to be treated. Should we put them on some immunosuppressive therapy or should we wait? At the moment this is a bit of a tautology. You know that if you put people on therapy from the very first event, some of those people are not going to have a second event. And some of the people are, but you’ve decreased the risk of them having that second (event) if your treatment is effective. So that’s what they’ve shown, which is great. But the question is, can you predict who’s going to have a second event and know who to put on treatment and not put on treatment? It’s too early to know, but this is a good start,” said Dr. Cossoy, assistant professor of ophthalmology at the University of Manitoba.

Dr. Bilodeau and Dr. Cossoy have no relevant financial disclosures.

SAN DIEGO – Epstein-Barr Virus (EBV) infection is widely recognized as a contributor to risk of multiple sclerosis (MS). Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.

That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.

At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
 

Reducing the risk of MS by targeting EBV

Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.

NIH

EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.

Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.

He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.

The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.

Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.

Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
 

Does EBV infection even matter?

In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.

Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.

Johns Hopkins Medicine

SAN DIEGO – Epstein-Barr Virus (EBV) infection is widely recognized as a contributor to risk of multiple sclerosis (MS). Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.

That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.

At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
 

Reducing the risk of MS by targeting EBV

Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.

NIH

EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.

Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.

He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.

The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.

Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.

Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
 

Does EBV infection even matter?

In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.

Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.

Johns Hopkins Medicine

SAN DIEGO – Epstein-Barr Virus (EBV) infection is widely recognized as a contributor to risk of multiple sclerosis (MS). Although most adults have been exposed, it is very rare to find MS in an individual with no prior EBV exposure.

That apparent relationship has driven interest in a vaccine against EBV in an effort to reduce MS incidence on a population level.

At a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), two researchers debated the potential benefits and pitfalls of such a program. The issues included the possible benefit in MS and other EBV-related conditions such as mononucleosis and various cancers, and whether EBV infection is a sufficient cause for MS, as well as concerns about vaccinating a healthy at-risk population.
 

Reducing the risk of MS by targeting EBV

Jeffrey I. Cohen, MD, spoke first, and cited several lines of evidence supporting the importance of EBV in MS. One study showed a 32-fold increased risk of MS following primary infection with EBV, and another showed that higher EBV nuclear antigen (EBNA) antibody titers were associated with a 36-fold higher risk of MS. “So we have two completely independent studies suggesting that EBV is really very important as a cofactor for development of MS,” said Dr. Cohen, chief of the laboratory of infectious diseases and chief of the medical virology section at the National Institutes of Health, Bethesda, Md.

NIH

EBV is also latent in B cells, and anti-B cell therapy is an effective therapeutic strategy for MS. However, the mechanism remains unknown.

Targeting EBV could involve attacking infected cells, or a therapeutic vaccine could be employed to treat EVB-infected individuals, similar to the shingles vaccine. “In all of these methods, one would end up with fewer EBV infected B cells and as a result, presumably you’d have reduced antigenic stimulation of EBV-infected B cells to stimulate either antibodies or T cells that could damage the nervous system. By reducing this, one might be able to [treat] multiple sclerosis,” said Dr. Cohen.

He did acknowledge concerns. It isn’t yet understood whether destroying EBV-infected cells would actually improve outcomes. It also may be more difficult to reduce a latent infection than to prevent infection, since almost all B cells become latently infected. “Thus we think perhaps a role for preventing infection or modifying the initial infection could be important,” said Dr. Cohen.

The most advanced vaccine candidate is a soluble form of EBV glycoprotein gp 350, which is the dominant glycoprotein on the surface of the virus and infected cells. It reduced the risk of mononucleosis by 78%, but it did not prevent EBV infection. There were no safety concerns. Two more vaccines are currently in clinical trials – an mRNA vaccine against a gp 350 sponsored by Moderna, and a gp 350 nanoparticle vaccine by the NIH.

Dr. Cohen acknowledged that safety is the most important factor, since it would be given to healthy individuals, and probably children. There are worries that a vaccine using EBV proteins could worsen MS. In particular, higher titers of antibodies against EBNA have been linked to developing MS and the anti-EBNA antibody has been implicated in molecular mimicry related to MS. However, the current vaccines avoid EBNA. Another worry is that a vaccine could delay onset of disease to an older age, when infection might be more dangerous. However, no delay in onset has been noted with the varicella vaccine or polio vaccines, which prompted similar concerns.

Vaccinating against EBV could also reduce other conditions such as mononucleosis and several cancers.
 

Does EBV infection even matter?

In his talk, Peter Calabresi, MD, made the case that EBV is not the sole cause of MS, and thus targeting it may prove ineffective. Dr. Calabresi is director of the division of neuroimmunology at Johns Hopkins Medicine, Baltimore.

Why was he asked to provide a rebuttal? “About this time last year, I commented at a meeting that we should be thoughtful as we think about what to do about EBV and MS. I do believe that constructive dialogue is the foundation of science,” he said. He also stated that he is not opposed to vaccines. “I congratulate Dr. Cohen on all of his vaccine successes,” he said.

Johns Hopkins Medicine

SAN DIEGO – Diagnosis of multiple sclerosis (MS) presents a number of challenges, and differential diagnosis is critical to get patients on therapy earlier in the disease process.

The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Mimics and red flags

Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.

Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.

These and other red flags should prompt a careful look to get the right diagnosis.
 

Earlier diagnosis = better outcomes

“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.

“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
 

Look for patterns and imaging clues

Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.

Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”

Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
 

Common mistakes

MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”

Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.

SAN DIEGO – Diagnosis of multiple sclerosis (MS) presents a number of challenges, and differential diagnosis is critical to get patients on therapy earlier in the disease process.

The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Mimics and red flags

Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.

Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.

These and other red flags should prompt a careful look to get the right diagnosis.
 

Earlier diagnosis = better outcomes

“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.

“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
 

Look for patterns and imaging clues

Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.

Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”

Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
 

Common mistakes

MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”

Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.

SAN DIEGO – Diagnosis of multiple sclerosis (MS) presents a number of challenges, and differential diagnosis is critical to get patients on therapy earlier in the disease process.

The problem is that MS can vary greatly in its presentation, and many symptoms can mimic other conditions, according to Eoin Flanagan, MBBCh, who discussed the issue during a session at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
 

Mimics and red flags

Dr. Flanagan noted a study that found common themes among MS misdiagnoses. “Many of these conditions are common conditions that we see in our neurology clinic – for example, migraine, fibromyalgia, nonspecific symptoms with an abnormal MRI, or functional neurologic disorder. If you’re teaching medical students or trainees about MS misdiagnosis, it’s important to give this example to show that these are not the zebras that are misdiagnosed, but actually common conditions that we see in our clinics,” said Dr. Flanagan, a neurologist at Mayo Clinic in Rochester, Minn.

Evaluation of MS mimics isn’t always necessary. Much of the time, typical clinical, neurologic, and imaging features provide a clear diagnosis. But some features can be red flags that MS may not be the cause. These can include a cerebrospinal fluid white blood cell count higher than 50, elevated CSF protein with normal white cell counts, low glucose, and negative oligoclonal bands, all of which could signify a range of other conditions.

These and other red flags should prompt a careful look to get the right diagnosis.
 

Earlier diagnosis = better outcomes

“[Evidence has] shown recently that as the diagnostic criteria have become more sensitive and we diagnose MS earlier, patients have had better outcomes because they’ve been able to initiate treatment earlier,” said Andrew Solomon, MD, who is an associate professor of neurologic sciences and division chief of multiple sclerosis at University of Vermont, Burlington. Dr. Solomon, Dr. Flanagan, and others are currently writing a review article on differential diagnosis of MS that will update the last review, published in 2008.

“Differential diagnosis has become more complex as we’ve had a broader understanding of disorders that can mimic MS. In the meantime, we still don’t have a highly sensitive and specific biomarker for MS that can help guide us when we first see somebody,” said Dr. Solomon.
 

Look for patterns and imaging clues

Dr. Flanagan’s talk had several points of emphasis. A key feature is the length of time between when the patient develops the first symptom and maximal symptoms. “If that’s very quick, then that suggests it’s a spinal cord stroke. If it comes down over days to a few weeks, then that suggests inflammation like MS, or like neuromyelitis optica [NMO] or myelin oligodendrocyte glycoprotein antibody-associated disease [MOGAD]. As it progresses beyond 21 days, then we’re going to be thinking about a different diagnosis,” said Dr. Flanagan.

Dr. Flanagan also noted the usefulness of specific features of the spinal cord MRI. Variables like lesion length, location in the center or periphery of the spinal cord, and characteristics of the enhancement pattern may be useful. “The pattern of gadolinium enhancement can be useful in narrowing your differential diagnosis and suggesting the correct diagnosis. For example, the flat pancake-like enhancement on sagittal images can suggest cervical spondylosis, while trident sign on axial images can suggest spinal cord sarcoidosis. Prior studies have shown that education on these patterns can enhance diagnosis.”

Dr. Flanagan suggested that both radiologists and neurologists should be trained to recognize such patterns. “If you educate radiologists or neurologists on these patterns, it can help them with diagnosis.”
 

Common mistakes

MOGAD and aquaporin 4–positive NMO spectrum disorder (AQP4+NMOSD) can be easily mistaken for MS, but there are some key differences. MOGAD and AQP4+NMOSD attacks are more severe than MS attacks, leaving patients more likely to be blind following an optic neuritis attack or wheelchair bound because of myelitis. More than 85% of CSF from patients with MS have oligoclonal bands versus about 15% of CSF from patients with MOGAD or AQP4+NMOSD. There is also a difference in lesion dynamics over time: MOGAD T2 lesions frequently resolve over follow-up while AQP4+NMOSD and MS lesions typically continue and leave a scar and persist. Silent lesions are more likely during surveillance MRI among MS patients, but are rare in MOGAD and AQP4+NMOSD, according to Dr. Flanagan. “One caveat to this is that with stronger MS medications we are seeing less silent lesions accumulating as we use those treatments more often.”

Dr. Solomon has been done nonpromotional speaking for EMD Serono. He has received research funding from Bristol-Myers Squibb. He has been on an advisory board or consulted for Greenwich Biosciences, TG Therapeutics, Octave Bioscience, and Horizon Therapeutics. Dr. Flanagan has no relevant financial disclosures. Dr. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB.

SAN DIEGO – Cognitive-behavioral therapy (CBT), the wakefulness-promoting drug modafinil (Provigil), and a combination of both treatments all reduce fatigue in patients with multiple sclerosis (MS) – but the combination has an edge when it comes to overall perceived benefits, new research shows.

As well, study results suggest that individuals with poorer sleep hygiene may benefit more from CBT, researchers noted.

“Clinicians should consider clinical characteristics and overall treatment goals when selecting fatigue interventions, to offer a more personalized approach for MS fatigue,” said study investigator Tiffany Braley, MD, associate professor of neurology, University of Michigan, Ann Arbor.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Incapacitating symptom

Dr. Braley noted that fatigue affects up to 90% of patients with MS and is the most incapacitating symptom for more than 40% of these patients. In addition, fatigue is a strong predictor of reduced work productivity, unemployment, reduced social participation, and reduced quality of life.

“Given the impact that fatigue has on the health and well-being of people with MS, it is essential to find ways to optimize the current treatments that we have at hand for fatigue in MS in the most patient-centered way possible,” Dr. Braley said.

CBT, which teaches strategies to target maladaptive thoughts and beliefs, is one of the most promising behavioral strategies, the investigators noted. It has been shown to be effective for multiple conditions including depression, posttraumatic stress disorder, insomnia, and pain.

For MS fatigue, CBT is considered a second-line treatment. Moderate and sustained efficacy have been shown across trials but access remains limited, Dr. Braley reported.

Modafinil, which is approved by the U.S. Food and Drug Administration to treat sleepiness secondary to obstructive sleep apnea and narcolepsy, is commonly used off-label to treat MS-related fatigue. However, prior trials have yielded mixed results regarding the efficacy of the drug for MS fatigue, said Dr. Braley.

Also, different behavioral and pharmacologic therapies have never been combined to determine if there might be a synergistic benefit, she added.

The new 12-week parallel-arm, analyst-blinded COMBO-MS trial included 336 participants (76.2% women; mean age, 48.8 years). Most of the patients (85.1%) were White and most (71.1%) had relapsing remitting MS (RRMS).

Participants were randomly assigned to receive 8 weekly and then two “booster” sessions of telephone-delivered one-on-one CBT, or modafinil with the dose generally ranging from 100 to 200 mg per day, or a combination of the two therapies.

The primary outcome measure was change in fatigue on the self-report Modified Fatigue Impact Scale (MFIS), using online surveys. The mean baseline MFIS was 52.7.

Study participants also completed questionnaires on disability, sleep disorders, sleep hygiene, and sleepiness (Epworth sleepiness scale).

Covariates included demographics, anxiety based on the Generalized Anxiety Disorder-7, pain score on the Brief Pain Inventory, baseline fatigue score, and physical activity.
 

Clinically, statistically significant

The overall treatment effect on the total MFIS score at 12 weeks was positive for each group. “Each treatment arm was associated with a clinically significant and a statistically significant within-group reduction in MSIF score from 15 to 17 points,” Dr. Braley reported.

“But even though the combination therapy ended up having the highest absolute reduction, it ultimately was not statistically significant,” she added.

Responder analyses showed almost two-thirds of each treatment group experienced at least a 10-point reduction in MSIF, which is considered clinically significant. In addition, more than 50% experienced at least 25% reduction in MSIF. “Again, although the combination therapy seemed to have a higher proportion of responders, this was not statistically significant,” said Dr. Braley.

A secondary outcome was the self-reported Patient Global Impression of Change, which rates overall symptoms and quality of life. More participants in all groups said their symptoms and quality of life at study’s end were somewhat better, moderately better, a definite improvement, or a great deal better.

But here the combination therapy was significantly better than the other interventions. “This suggests there may be more subjective benefits of combination therapy that we’re not capturing” with other measures, Dr. Braley noted.

Sleep hygiene significantly moderated the treatment effect (P = .03). As sleep hygiene worsened, the effect of modafinil monotherapy relative to CBT monotherapy appeared to diminish, and behavior therapy started to have more benefit relative to modafinil therapy, the investigators noted.

“Our results suggest that people with MS who have problems maintaining healthy sleep behaviors could potentially see more benefit from behaviorally based treatments that target sleep habits as part of the fatigue management plan, as opposed to a stimulant medication that could make sleep more difficult to maintain,” Dr. Braley said.

“On the other hand, people with good sleep hygiene may sufficiently respond to modafinil. For those who believe their mood, activity limitations, and quality of life are closely linked to their fatigue, combination therapy may offer more global benefits,” she added.

Sleepiness, as assessed with the Epworth sleepiness scale, had a direct effect on treatment response (P = .0087) that did not vary by intervention. Those who were sleepier had greater reductions on MSIF scores.

Dr. Braley noted that there was an excellent adherence rate, with only 26 participants discontinuing the study. Of these, 20 were from the modafinil group and discontinued because of side effects, and 6 were from the CBT group and discontinued because of time constraints. There were no serious adverse events reported.
 

Important lifestyle factor

Session cochair Deepak Kaushik, PhD, of the department of biomedical sciences, Memorial University, St John’s, Nfld., said the benefit of CBT for MS fatigue “definitely needs to be looked into further.”

Sleep deprivation, along with ensuing fatigue, is among the lifestyle factors that play a vital role in MS, said Dr. Kaushik, who was not involved with the research.

The effect of CBT on fatigue is likely through stress reduction, he said, adding that the immune system is significantly affected by stress. “We know the immune system has a direct linkage to the way you feel [and] your stress response to situations,” so it makes sense that CBT lowers fatigue because it reduces stress, Dr. Kaushik said.

The study received funding from the Patient-Centered Outcomes Research Institute. Dr. Braley and Dr. Kaushik have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Cognitive-behavioral therapy (CBT), the wakefulness-promoting drug modafinil (Provigil), and a combination of both treatments all reduce fatigue in patients with multiple sclerosis (MS) – but the combination has an edge when it comes to overall perceived benefits, new research shows.

As well, study results suggest that individuals with poorer sleep hygiene may benefit more from CBT, researchers noted.

“Clinicians should consider clinical characteristics and overall treatment goals when selecting fatigue interventions, to offer a more personalized approach for MS fatigue,” said study investigator Tiffany Braley, MD, associate professor of neurology, University of Michigan, Ann Arbor.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Incapacitating symptom

Dr. Braley noted that fatigue affects up to 90% of patients with MS and is the most incapacitating symptom for more than 40% of these patients. In addition, fatigue is a strong predictor of reduced work productivity, unemployment, reduced social participation, and reduced quality of life.

“Given the impact that fatigue has on the health and well-being of people with MS, it is essential to find ways to optimize the current treatments that we have at hand for fatigue in MS in the most patient-centered way possible,” Dr. Braley said.

CBT, which teaches strategies to target maladaptive thoughts and beliefs, is one of the most promising behavioral strategies, the investigators noted. It has been shown to be effective for multiple conditions including depression, posttraumatic stress disorder, insomnia, and pain.

For MS fatigue, CBT is considered a second-line treatment. Moderate and sustained efficacy have been shown across trials but access remains limited, Dr. Braley reported.

Modafinil, which is approved by the U.S. Food and Drug Administration to treat sleepiness secondary to obstructive sleep apnea and narcolepsy, is commonly used off-label to treat MS-related fatigue. However, prior trials have yielded mixed results regarding the efficacy of the drug for MS fatigue, said Dr. Braley.

Also, different behavioral and pharmacologic therapies have never been combined to determine if there might be a synergistic benefit, she added.

The new 12-week parallel-arm, analyst-blinded COMBO-MS trial included 336 participants (76.2% women; mean age, 48.8 years). Most of the patients (85.1%) were White and most (71.1%) had relapsing remitting MS (RRMS).

Participants were randomly assigned to receive 8 weekly and then two “booster” sessions of telephone-delivered one-on-one CBT, or modafinil with the dose generally ranging from 100 to 200 mg per day, or a combination of the two therapies.

The primary outcome measure was change in fatigue on the self-report Modified Fatigue Impact Scale (MFIS), using online surveys. The mean baseline MFIS was 52.7.

Study participants also completed questionnaires on disability, sleep disorders, sleep hygiene, and sleepiness (Epworth sleepiness scale).

Covariates included demographics, anxiety based on the Generalized Anxiety Disorder-7, pain score on the Brief Pain Inventory, baseline fatigue score, and physical activity.
 

Clinically, statistically significant

The overall treatment effect on the total MFIS score at 12 weeks was positive for each group. “Each treatment arm was associated with a clinically significant and a statistically significant within-group reduction in MSIF score from 15 to 17 points,” Dr. Braley reported.

“But even though the combination therapy ended up having the highest absolute reduction, it ultimately was not statistically significant,” she added.

Responder analyses showed almost two-thirds of each treatment group experienced at least a 10-point reduction in MSIF, which is considered clinically significant. In addition, more than 50% experienced at least 25% reduction in MSIF. “Again, although the combination therapy seemed to have a higher proportion of responders, this was not statistically significant,” said Dr. Braley.

A secondary outcome was the self-reported Patient Global Impression of Change, which rates overall symptoms and quality of life. More participants in all groups said their symptoms and quality of life at study’s end were somewhat better, moderately better, a definite improvement, or a great deal better.

But here the combination therapy was significantly better than the other interventions. “This suggests there may be more subjective benefits of combination therapy that we’re not capturing” with other measures, Dr. Braley noted.

Sleep hygiene significantly moderated the treatment effect (P = .03). As sleep hygiene worsened, the effect of modafinil monotherapy relative to CBT monotherapy appeared to diminish, and behavior therapy started to have more benefit relative to modafinil therapy, the investigators noted.

“Our results suggest that people with MS who have problems maintaining healthy sleep behaviors could potentially see more benefit from behaviorally based treatments that target sleep habits as part of the fatigue management plan, as opposed to a stimulant medication that could make sleep more difficult to maintain,” Dr. Braley said.

“On the other hand, people with good sleep hygiene may sufficiently respond to modafinil. For those who believe their mood, activity limitations, and quality of life are closely linked to their fatigue, combination therapy may offer more global benefits,” she added.

Sleepiness, as assessed with the Epworth sleepiness scale, had a direct effect on treatment response (P = .0087) that did not vary by intervention. Those who were sleepier had greater reductions on MSIF scores.

Dr. Braley noted that there was an excellent adherence rate, with only 26 participants discontinuing the study. Of these, 20 were from the modafinil group and discontinued because of side effects, and 6 were from the CBT group and discontinued because of time constraints. There were no serious adverse events reported.
 

Important lifestyle factor

Session cochair Deepak Kaushik, PhD, of the department of biomedical sciences, Memorial University, St John’s, Nfld., said the benefit of CBT for MS fatigue “definitely needs to be looked into further.”

Sleep deprivation, along with ensuing fatigue, is among the lifestyle factors that play a vital role in MS, said Dr. Kaushik, who was not involved with the research.

The effect of CBT on fatigue is likely through stress reduction, he said, adding that the immune system is significantly affected by stress. “We know the immune system has a direct linkage to the way you feel [and] your stress response to situations,” so it makes sense that CBT lowers fatigue because it reduces stress, Dr. Kaushik said.

The study received funding from the Patient-Centered Outcomes Research Institute. Dr. Braley and Dr. Kaushik have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Cognitive-behavioral therapy (CBT), the wakefulness-promoting drug modafinil (Provigil), and a combination of both treatments all reduce fatigue in patients with multiple sclerosis (MS) – but the combination has an edge when it comes to overall perceived benefits, new research shows.

As well, study results suggest that individuals with poorer sleep hygiene may benefit more from CBT, researchers noted.

“Clinicians should consider clinical characteristics and overall treatment goals when selecting fatigue interventions, to offer a more personalized approach for MS fatigue,” said study investigator Tiffany Braley, MD, associate professor of neurology, University of Michigan, Ann Arbor.

The findings were presented at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Incapacitating symptom

Dr. Braley noted that fatigue affects up to 90% of patients with MS and is the most incapacitating symptom for more than 40% of these patients. In addition, fatigue is a strong predictor of reduced work productivity, unemployment, reduced social participation, and reduced quality of life.

“Given the impact that fatigue has on the health and well-being of people with MS, it is essential to find ways to optimize the current treatments that we have at hand for fatigue in MS in the most patient-centered way possible,” Dr. Braley said.

CBT, which teaches strategies to target maladaptive thoughts and beliefs, is one of the most promising behavioral strategies, the investigators noted. It has been shown to be effective for multiple conditions including depression, posttraumatic stress disorder, insomnia, and pain.

For MS fatigue, CBT is considered a second-line treatment. Moderate and sustained efficacy have been shown across trials but access remains limited, Dr. Braley reported.

Modafinil, which is approved by the U.S. Food and Drug Administration to treat sleepiness secondary to obstructive sleep apnea and narcolepsy, is commonly used off-label to treat MS-related fatigue. However, prior trials have yielded mixed results regarding the efficacy of the drug for MS fatigue, said Dr. Braley.

Also, different behavioral and pharmacologic therapies have never been combined to determine if there might be a synergistic benefit, she added.

The new 12-week parallel-arm, analyst-blinded COMBO-MS trial included 336 participants (76.2% women; mean age, 48.8 years). Most of the patients (85.1%) were White and most (71.1%) had relapsing remitting MS (RRMS).

Participants were randomly assigned to receive 8 weekly and then two “booster” sessions of telephone-delivered one-on-one CBT, or modafinil with the dose generally ranging from 100 to 200 mg per day, or a combination of the two therapies.

The primary outcome measure was change in fatigue on the self-report Modified Fatigue Impact Scale (MFIS), using online surveys. The mean baseline MFIS was 52.7.

Study participants also completed questionnaires on disability, sleep disorders, sleep hygiene, and sleepiness (Epworth sleepiness scale).

Covariates included demographics, anxiety based on the Generalized Anxiety Disorder-7, pain score on the Brief Pain Inventory, baseline fatigue score, and physical activity.
 

Clinically, statistically significant

The overall treatment effect on the total MFIS score at 12 weeks was positive for each group. “Each treatment arm was associated with a clinically significant and a statistically significant within-group reduction in MSIF score from 15 to 17 points,” Dr. Braley reported.

“But even though the combination therapy ended up having the highest absolute reduction, it ultimately was not statistically significant,” she added.

Responder analyses showed almost two-thirds of each treatment group experienced at least a 10-point reduction in MSIF, which is considered clinically significant. In addition, more than 50% experienced at least 25% reduction in MSIF. “Again, although the combination therapy seemed to have a higher proportion of responders, this was not statistically significant,” said Dr. Braley.

A secondary outcome was the self-reported Patient Global Impression of Change, which rates overall symptoms and quality of life. More participants in all groups said their symptoms and quality of life at study’s end were somewhat better, moderately better, a definite improvement, or a great deal better.

But here the combination therapy was significantly better than the other interventions. “This suggests there may be more subjective benefits of combination therapy that we’re not capturing” with other measures, Dr. Braley noted.

Sleep hygiene significantly moderated the treatment effect (P = .03). As sleep hygiene worsened, the effect of modafinil monotherapy relative to CBT monotherapy appeared to diminish, and behavior therapy started to have more benefit relative to modafinil therapy, the investigators noted.

“Our results suggest that people with MS who have problems maintaining healthy sleep behaviors could potentially see more benefit from behaviorally based treatments that target sleep habits as part of the fatigue management plan, as opposed to a stimulant medication that could make sleep more difficult to maintain,” Dr. Braley said.

“On the other hand, people with good sleep hygiene may sufficiently respond to modafinil. For those who believe their mood, activity limitations, and quality of life are closely linked to their fatigue, combination therapy may offer more global benefits,” she added.

Sleepiness, as assessed with the Epworth sleepiness scale, had a direct effect on treatment response (P = .0087) that did not vary by intervention. Those who were sleepier had greater reductions on MSIF scores.

Dr. Braley noted that there was an excellent adherence rate, with only 26 participants discontinuing the study. Of these, 20 were from the modafinil group and discontinued because of side effects, and 6 were from the CBT group and discontinued because of time constraints. There were no serious adverse events reported.
 

Important lifestyle factor

Session cochair Deepak Kaushik, PhD, of the department of biomedical sciences, Memorial University, St John’s, Nfld., said the benefit of CBT for MS fatigue “definitely needs to be looked into further.”

Sleep deprivation, along with ensuing fatigue, is among the lifestyle factors that play a vital role in MS, said Dr. Kaushik, who was not involved with the research.

The effect of CBT on fatigue is likely through stress reduction, he said, adding that the immune system is significantly affected by stress. “We know the immune system has a direct linkage to the way you feel [and] your stress response to situations,” so it makes sense that CBT lowers fatigue because it reduces stress, Dr. Kaushik said.

The study received funding from the Patient-Centered Outcomes Research Institute. Dr. Braley and Dr. Kaushik have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Both public and private health plans score poorly when it comes to providing access to autoimmune medication, according to a report commissioned by the Autoimmune Association and Let My Doctors Decide, a national partnership of health care professionals. The analysis, published Jan. 26, found that 75% of insurers in the United States have policies that can limit coverage for Food and Drug Administration–approved medications for Crohn’s disease, lupus nephritis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.

“Choice among health plans is a hallmark of the American health insurance system, yet this analysis shows that people living with autoimmune conditions have few, if any, coverage choices that do not involve significant to severe access restrictions,” the authors wrote.

The study looked at three common utilization management policies by health plans that can limit coverage of certain medications: step therapy, formulary/tier placement, and prior authorization. To compare health plans, researchers weighted these policies using a point system. Each medication indicated for each condition was given a score of 0-4 based on access restrictions in a health plan. If a plan used step therapy, it received one point, and requiring prior authorization added an additional point. They also added points based on where a drug appeared on a plan’s formulary. A lower total score meant fewer access barriers. The numbers were then added, and each health plan received a grade of A, B, C, or F based on their average score. The datasets and analysis were provided and performed by the data analytics firm MMIT.

Nearly 9 in 10 Medicare plans received a C or worse for coverage of medication received via mail order or the pharmacy. In commercial plans, the majority of plans scored Cs or Fs for six of the seven conditions, excluding lupus nephritis, where 67% of all commercial health plans scored a B for access to these medications.

Physician-administered medications tended to receive poorer coverage than drugs received via pharmacy. Across all conditions, 65% of Medicare Advantage plans scored an F for physician-administered medication access. For both psoriasis and multiple sclerosis, at least 80% of Medicare plans earned failing scores because of these restrictions. Coverage was poorer on both commercial and health exchange plans, where across all conditions, 83% achieved failing scores. Two exceptions were the Southern and Northern California PPO plans by the Kaiser Foundation Health Plan. Out of the largest 25 health plans in the United States, these two plans earned As in coverage for physician-administered medications across all seven autoimmune conditions.

The report shows “a growing disconnect between science and health insurance benefit designs that were developed in the 1960s and 1970s,” Kenneth Thorpe, PhD, of Emory University, Atlanta, said in an interview. Insurers originally designed these benefits to prevent excessive utilization in a population of mostly acutely ill patients, he said, whereas now, 90% of healthcare spending is linked to chronic conditions. For these patients, research shows that incentivizing patients to adhere to medications results in fewer hospitalizations and, therefore, more cost savings, Thorpe noted. These plans also do not consider that there is no average patient, he said, and healthcare providers should be able to match each patient to the best treatment option for them rather than trying out other less expensive medications first. “To the extent that physicians can have the flexibility to provide medications and treatments to patients that are going to have the best clinical response, that’s better outcomes at lower cost,” Dr. Thorpe said. While research shows heterogeneity in patient outcomes with different medication, “benefit designs from the past just don’t recognize that.”

Neither America’s Health Insurance Plans nor Pharmaceutical Care Management Association responded to a request for comment.

Quardricos Driskell, executive director of Let My Doctors Decide and vice president of government relations and public policy at the Autoimmune Association, hopes the study will spur action by policy makers and health plans to improve access to medications for the people who need them. Another larger point of the report is to “uphold the sanctity of protecting the doctor and patient relationship,” he said in an interview, adding “that decisions fundamentally need to be made not by insurance plans or middleman pharmacy benefit managers, but by the provider and patient.”

Mr. Driskell and Dr. Thorpe reported no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Both public and private health plans score poorly when it comes to providing access to autoimmune medication, according to a report commissioned by the Autoimmune Association and Let My Doctors Decide, a national partnership of health care professionals. The analysis, published Jan. 26, found that 75% of insurers in the United States have policies that can limit coverage for Food and Drug Administration–approved medications for Crohn’s disease, lupus nephritis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.

“Choice among health plans is a hallmark of the American health insurance system, yet this analysis shows that people living with autoimmune conditions have few, if any, coverage choices that do not involve significant to severe access restrictions,” the authors wrote.

The study looked at three common utilization management policies by health plans that can limit coverage of certain medications: step therapy, formulary/tier placement, and prior authorization. To compare health plans, researchers weighted these policies using a point system. Each medication indicated for each condition was given a score of 0-4 based on access restrictions in a health plan. If a plan used step therapy, it received one point, and requiring prior authorization added an additional point. They also added points based on where a drug appeared on a plan’s formulary. A lower total score meant fewer access barriers. The numbers were then added, and each health plan received a grade of A, B, C, or F based on their average score. The datasets and analysis were provided and performed by the data analytics firm MMIT.

Nearly 9 in 10 Medicare plans received a C or worse for coverage of medication received via mail order or the pharmacy. In commercial plans, the majority of plans scored Cs or Fs for six of the seven conditions, excluding lupus nephritis, where 67% of all commercial health plans scored a B for access to these medications.

Physician-administered medications tended to receive poorer coverage than drugs received via pharmacy. Across all conditions, 65% of Medicare Advantage plans scored an F for physician-administered medication access. For both psoriasis and multiple sclerosis, at least 80% of Medicare plans earned failing scores because of these restrictions. Coverage was poorer on both commercial and health exchange plans, where across all conditions, 83% achieved failing scores. Two exceptions were the Southern and Northern California PPO plans by the Kaiser Foundation Health Plan. Out of the largest 25 health plans in the United States, these two plans earned As in coverage for physician-administered medications across all seven autoimmune conditions.

The report shows “a growing disconnect between science and health insurance benefit designs that were developed in the 1960s and 1970s,” Kenneth Thorpe, PhD, of Emory University, Atlanta, said in an interview. Insurers originally designed these benefits to prevent excessive utilization in a population of mostly acutely ill patients, he said, whereas now, 90% of healthcare spending is linked to chronic conditions. For these patients, research shows that incentivizing patients to adhere to medications results in fewer hospitalizations and, therefore, more cost savings, Thorpe noted. These plans also do not consider that there is no average patient, he said, and healthcare providers should be able to match each patient to the best treatment option for them rather than trying out other less expensive medications first. “To the extent that physicians can have the flexibility to provide medications and treatments to patients that are going to have the best clinical response, that’s better outcomes at lower cost,” Dr. Thorpe said. While research shows heterogeneity in patient outcomes with different medication, “benefit designs from the past just don’t recognize that.”

Neither America’s Health Insurance Plans nor Pharmaceutical Care Management Association responded to a request for comment.

Quardricos Driskell, executive director of Let My Doctors Decide and vice president of government relations and public policy at the Autoimmune Association, hopes the study will spur action by policy makers and health plans to improve access to medications for the people who need them. Another larger point of the report is to “uphold the sanctity of protecting the doctor and patient relationship,” he said in an interview, adding “that decisions fundamentally need to be made not by insurance plans or middleman pharmacy benefit managers, but by the provider and patient.”

Mr. Driskell and Dr. Thorpe reported no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Both public and private health plans score poorly when it comes to providing access to autoimmune medication, according to a report commissioned by the Autoimmune Association and Let My Doctors Decide, a national partnership of health care professionals. The analysis, published Jan. 26, found that 75% of insurers in the United States have policies that can limit coverage for Food and Drug Administration–approved medications for Crohn’s disease, lupus nephritis, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.

“Choice among health plans is a hallmark of the American health insurance system, yet this analysis shows that people living with autoimmune conditions have few, if any, coverage choices that do not involve significant to severe access restrictions,” the authors wrote.

The study looked at three common utilization management policies by health plans that can limit coverage of certain medications: step therapy, formulary/tier placement, and prior authorization. To compare health plans, researchers weighted these policies using a point system. Each medication indicated for each condition was given a score of 0-4 based on access restrictions in a health plan. If a plan used step therapy, it received one point, and requiring prior authorization added an additional point. They also added points based on where a drug appeared on a plan’s formulary. A lower total score meant fewer access barriers. The numbers were then added, and each health plan received a grade of A, B, C, or F based on their average score. The datasets and analysis were provided and performed by the data analytics firm MMIT.

Nearly 9 in 10 Medicare plans received a C or worse for coverage of medication received via mail order or the pharmacy. In commercial plans, the majority of plans scored Cs or Fs for six of the seven conditions, excluding lupus nephritis, where 67% of all commercial health plans scored a B for access to these medications.

Physician-administered medications tended to receive poorer coverage than drugs received via pharmacy. Across all conditions, 65% of Medicare Advantage plans scored an F for physician-administered medication access. For both psoriasis and multiple sclerosis, at least 80% of Medicare plans earned failing scores because of these restrictions. Coverage was poorer on both commercial and health exchange plans, where across all conditions, 83% achieved failing scores. Two exceptions were the Southern and Northern California PPO plans by the Kaiser Foundation Health Plan. Out of the largest 25 health plans in the United States, these two plans earned As in coverage for physician-administered medications across all seven autoimmune conditions.

The report shows “a growing disconnect between science and health insurance benefit designs that were developed in the 1960s and 1970s,” Kenneth Thorpe, PhD, of Emory University, Atlanta, said in an interview. Insurers originally designed these benefits to prevent excessive utilization in a population of mostly acutely ill patients, he said, whereas now, 90% of healthcare spending is linked to chronic conditions. For these patients, research shows that incentivizing patients to adhere to medications results in fewer hospitalizations and, therefore, more cost savings, Thorpe noted. These plans also do not consider that there is no average patient, he said, and healthcare providers should be able to match each patient to the best treatment option for them rather than trying out other less expensive medications first. “To the extent that physicians can have the flexibility to provide medications and treatments to patients that are going to have the best clinical response, that’s better outcomes at lower cost,” Dr. Thorpe said. While research shows heterogeneity in patient outcomes with different medication, “benefit designs from the past just don’t recognize that.”

Neither America’s Health Insurance Plans nor Pharmaceutical Care Management Association responded to a request for comment.

Quardricos Driskell, executive director of Let My Doctors Decide and vice president of government relations and public policy at the Autoimmune Association, hopes the study will spur action by policy makers and health plans to improve access to medications for the people who need them. Another larger point of the report is to “uphold the sanctity of protecting the doctor and patient relationship,” he said in an interview, adding “that decisions fundamentally need to be made not by insurance plans or middleman pharmacy benefit managers, but by the provider and patient.”

Mr. Driskell and Dr. Thorpe reported no relevant financial relationships. 

A version of this article first appeared on Medscape.com.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults, occurring more frequently in women than men. The development of anti-cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) in recent years has significantly changed the way we treat MS. Compared to older standards of care, such as chemotherapy and immunosuppressive drugs, anti-CD20 mAbs have been shown to be more effective in treating MS with fewer side effects. 

Data have shown that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and the cross-regulation of T-helper cells. CD20 is a protein that is expressed on the surface of B cells. Since B cells express the surface molecule CD20 at all points of differentiation, they provide a specific target for mAbs and are used to treat certain types of cancer and autoimmune disorders, including MS.

In people living with MS, the immune system mistakenly attacks the myelin sheath, a protective layer that surrounds nerve fibers in the central nervous system. This attack can cause inflammation and damage to the myelin sheath, leading to the development of various symptoms such as muscle weakness, vision problems, and issues with coordination and balance.

Anti-CD20 antibodies work by targeting and destroying B cells, which play a role in the immune system's attack on the myelin sheath. By targeting and destroying these cells, anti-CD20 antibodies may help to reduce the inflammation and damage to the myelin sheath and improve symptoms of MS.

There are several anti-CD20 mAbs used for the treatment of MS, including ocrelizumab, ofatumumab, ublituximab, and rituximab. Each drug has a unique mechanism of action and safety profile and distinct monitoring requirements. These therapies have been shown to deplete circulating B cells significantly for a certain amount of time, and they may be used in combination with other medications to treat MS. 

Ocrelizumab, a humanized anti-CD20 mAb administered by intravenous (IV) infusion, was approved in March 2017 by the US Food and Drug Administration (FDA) and is the first proven treatment to reduce disability progression in both primary progressive MS and relapsing MS. Interestingly, ocrelizumab binds to a CD20 epitope that overlaps partially with the epitope to which rituximab binds.

Ofatumumab is the first fully human anti-CD20 mAb and was approved by the FDA in August 2020 for treating relapsing forms of MS. The approval was on the basis of data from the phase 3 ASCLEPIOS I and II trials, which compared ofatumumab with teriflunomide, an oral agent that reduces the activity of proliferating T lymphocytes and B lymphocytes, mitigating the overall inflammatory response in MS. Subcutaneous ofatumumab demonstrated better efficacy than oral teriflunomide in reducing the annualized relapse rate in patients with MS. 

Ublituximab was recently approved by the FDA for treatment of relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS. Ublituximab works much like other anti-CD20 antibodies; however, it has been glycoengineered so that certain altered sugar molecules attached to the antibody increase its effectiveness. 

Rituximab is a chimeric monoclonal B-cell–depleting anti-CD20 antibody that has also showed promise as an escalation and as a first-line therapy for MS. The FDA has not approved it for this specific use yet, so its use is considered “off label.” A 2017 study showed that ofatumumab was more effective at depleting B cells than high doses of IV rituximab. 

It is important to note that anti-CD20 antibodies are not a cure for MS, and although they show promise for some patients, these agents do not work for everyone. The progress, severity, and specific symptoms of MS in any individual cannot yet be predicted; however, advances in research and treatment are leading to better understanding and moving us closer to curing this unpredictable, debilitating disease.

An agent biologically similar to the humanized monoclonal antibody natalizumab is as effective and safe as the original reference drug for relapsing remitting multiple sclerosis (RRMS) – and has a similar level of immunogenicity, new research shows.

The investigators noted that these phase 3 trial findings are the final stage in the regulatory approval process.

“There will be a biosimilar that with respect to all parameters – efficacy, side effects, immunogenicity – doesn’t differ from the original drug and will probably be an option to consider to reduce treatment costs in MS,” said lead investigator Bernhard Hemmer, MD, a professor in the department of neurology, Technical University of Munich (Germany).

The findings were published online in JAMA Neurology.
 

Potential cost savings

Disease-modifying therapies (DMTs), particularly targeted biologics, have revolutionized the treatment of MS, including RRMS. Natalizumab, which was the first targeted biologic therapy approved for RRMS, is very effective and widely used, Dr. Hemmer said.

However, this and other DMTs are costly. Biosimilars, which are medicines clinically similar to an already marketed reference biologic medicine, can address this issue. In the areas of rheumatology and oncology, biosimilars have already demonstrated significant cost savings and improved treatment access.

The biosimilar natalizumab (biosim-NTZ), developed by Polpharma Biologics, is the first biosimilar monoclonal antibody therapy to be developed for MS.

Health authorities such as the Food and Drug Administration require comparative phase 3 studies to confirm there are no clinically relevant differences between a proposed biosimilar and its reference medicine.

The new multicenter, phase 3, double-blind, randomized trial – known as Antelope – included 264 adult patients with RRMS at 48 centers in seven Eastern European countries. Most study participants were women (61.4%), and their mean age was 36.7 years.

All study participants were randomly assigned to receive intravenous infusions every 4 weeks of 300 mg of biosim-NTZ or reference natalizumab (ref-NTZ) for a total of 12 infusions.

At week 24, 30 patients were switched from ref-NTZ to biosim-NTZ for the remainder of their infusions. Including such a population is required by regulatory agencies to ensure switching patients from a drug they’ve been taking to a new biosimilar does not introduce any concerns, said Dr. Hemmer.
 

Comparable efficacy, safety profile

The primary efficacy endpoint was the cumulative number of new active brain lesions on MRI.

At baseline, 48.1% of the biosimilar group and 45.9% of the reference drug group had at least one gadolinium-enhancing lesion. In addition, 96.9% of the biosimilar group had more than 15 T2 lesions, compared with 96.2% of the reference group.

At week 24, the mean difference between biosim-NTZ and ref-NTZ in the cumulative number of new active lesions was 0.17 (least square means, 0.34 vs. 0.45), with a 95% confidence interval of –0.61 to 0.94 and a point estimate within the prespecified margins of ± 2.1.

The annualized relapse rate for biosim-NTZ and ref-NTZ was similar at 24 weeks (0.21 vs. 0.15), as well as at 48 weeks (0.17 vs. 0.13). For Expanded Disability Status Scale scores, which were similar between treatment groups at baseline (mean, 3.4 vs. 3.2), change at 24 and 48 weeks was minimal and similar in both groups.

The safety profile was as expected for patients with RRMS receiving natalizumab. There were few adverse events of special interest, with similar proportions across all treatment groups.

The overall adverse-event profile for patients who switched from ref-NTZ to biosim-NTZ was similar to patients continuing ref-NTZ treatment and did not indicate any new or increased risks associated with switching.

Rates of treatment-emergent adverse events (TEAEs) were similar, at 64.9% for biosim-NTZ, 68.9% for ref-NTZ, and 73.3% for the switch group. The most-reported TEAEs among all treatment groups were nervous system disorders and infections and infestations.

Progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal demyelinating disease of the central nervous system, is associated with some DMTs – notably ref-NTZ. It is caused by infection with the John Cunningham virus (JCV) (also referred to as human polyomavirus), the researchers noted.

As per the study protocol, no participant had a JCV-positive index of more than 1.5 at baseline. Proportions of patients positive for anti-JCV antibodies were similarly distributed between treatment groups throughout the study.
 

Similar immunogenicity

There was strong concordance regarding positivity for treatment-emergent antidrug antibodies between the biosim-NTZ and ref-NTZ groups (79.4% and 74.0%). This was also the case for antinatalizumab-neutralizing antibodies (69.0% and 66.2%).

“There was nothing that indicated immunogenicity is different” between the two agents, said Dr. Hemmer.

While this might change “when you look at longer time periods,” antibodies to natalizumab usually develop “very early on,” he added.

Dr. Hemmer noted that this comparison of the proposed biosimilar with the reference drug had no real surprises.

“If the immunogenicity is the same, the mode of action is the same, and the dose is the same, you would expect to have a similar clinical effect and also a similar side-effect profile, which is indeed the case,” he said.

Dr. Hemmer added that he has no insight as to when the drug might be approved but believes developers expect that to occur sometime this year.
 

Welcome results

Commenting on the study results, Torge Rempe, MD, assistant professor in the department of neurology, University of Florida, Gainesville, and the William T. And Janice M. Neely professor for research in MS, said he welcomes these new results showing the biosimilar matched the reference medication.

“The authors report no significant difference in their primary endpoint of cumulative number of active lesions as well as their secondary clinical endpoints of annualized relapse rate and changes from baseline Expanded Disability Status Scale scores,” said Dr. Rempe, who was not involved with the research.

The study also showed the reported adverse events were similar between the biosimilar and reference natalizumab, he noted.

However, although no cases of PML were uncovered during the study period, further research is needed to determine long-term safety in this area, Dr. Rempe said.

Finally, he agreed that the development of biosimilars such as this one addresses the issue of high annual costs for DMTs, an area of concern in the field of MS.

The study was funded by Polpharma Biologics. Dr. Hemmer has reported receiving personal fees from Polpharma and Sandoz during the conduct of the study and personal fees from Novartis, Biocom, and TG Therapeutics outside the submitted work. He has also received a patent for genetic determinants of antibodies against interferon-beta and a patent for KIR4.1 antibodies in MS; served on scientific advisory boards for Novartis; served as a data monitoring and safety committee member for AllergyCare, Polpharma Biologics, Sandoz, and TG Therapeutics; and received speaker honoraria from Desitin, grants from Regeneron for MS research, and funding from the Multiple MS EU consortium, the CLINSPECT-M consortium, and the German Research Foundation. Dr. Rempe has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An agent biologically similar to the humanized monoclonal antibody natalizumab is as effective and safe as the original reference drug for relapsing remitting multiple sclerosis (RRMS) – and has a similar level of immunogenicity, new research shows.

The investigators noted that these phase 3 trial findings are the final stage in the regulatory approval process.

“There will be a biosimilar that with respect to all parameters – efficacy, side effects, immunogenicity – doesn’t differ from the original drug and will probably be an option to consider to reduce treatment costs in MS,” said lead investigator Bernhard Hemmer, MD, a professor in the department of neurology, Technical University of Munich (Germany).

The findings were published online in JAMA Neurology.
 

Potential cost savings

Disease-modifying therapies (DMTs), particularly targeted biologics, have revolutionized the treatment of MS, including RRMS. Natalizumab, which was the first targeted biologic therapy approved for RRMS, is very effective and widely used, Dr. Hemmer said.

However, this and other DMTs are costly. Biosimilars, which are medicines clinically similar to an already marketed reference biologic medicine, can address this issue. In the areas of rheumatology and oncology, biosimilars have already demonstrated significant cost savings and improved treatment access.

The biosimilar natalizumab (biosim-NTZ), developed by Polpharma Biologics, is the first biosimilar monoclonal antibody therapy to be developed for MS.

Health authorities such as the Food and Drug Administration require comparative phase 3 studies to confirm there are no clinically relevant differences between a proposed biosimilar and its reference medicine.

The new multicenter, phase 3, double-blind, randomized trial – known as Antelope – included 264 adult patients with RRMS at 48 centers in seven Eastern European countries. Most study participants were women (61.4%), and their mean age was 36.7 years.

All study participants were randomly assigned to receive intravenous infusions every 4 weeks of 300 mg of biosim-NTZ or reference natalizumab (ref-NTZ) for a total of 12 infusions.

At week 24, 30 patients were switched from ref-NTZ to biosim-NTZ for the remainder of their infusions. Including such a population is required by regulatory agencies to ensure switching patients from a drug they’ve been taking to a new biosimilar does not introduce any concerns, said Dr. Hemmer.
 

Comparable efficacy, safety profile

The primary efficacy endpoint was the cumulative number of new active brain lesions on MRI.

At baseline, 48.1% of the biosimilar group and 45.9% of the reference drug group had at least one gadolinium-enhancing lesion. In addition, 96.9% of the biosimilar group had more than 15 T2 lesions, compared with 96.2% of the reference group.

At week 24, the mean difference between biosim-NTZ and ref-NTZ in the cumulative number of new active lesions was 0.17 (least square means, 0.34 vs. 0.45), with a 95% confidence interval of –0.61 to 0.94 and a point estimate within the prespecified margins of ± 2.1.

The annualized relapse rate for biosim-NTZ and ref-NTZ was similar at 24 weeks (0.21 vs. 0.15), as well as at 48 weeks (0.17 vs. 0.13). For Expanded Disability Status Scale scores, which were similar between treatment groups at baseline (mean, 3.4 vs. 3.2), change at 24 and 48 weeks was minimal and similar in both groups.

The safety profile was as expected for patients with RRMS receiving natalizumab. There were few adverse events of special interest, with similar proportions across all treatment groups.

The overall adverse-event profile for patients who switched from ref-NTZ to biosim-NTZ was similar to patients continuing ref-NTZ treatment and did not indicate any new or increased risks associated with switching.

Rates of treatment-emergent adverse events (TEAEs) were similar, at 64.9% for biosim-NTZ, 68.9% for ref-NTZ, and 73.3% for the switch group. The most-reported TEAEs among all treatment groups were nervous system disorders and infections and infestations.

Progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal demyelinating disease of the central nervous system, is associated with some DMTs – notably ref-NTZ. It is caused by infection with the John Cunningham virus (JCV) (also referred to as human polyomavirus), the researchers noted.

As per the study protocol, no participant had a JCV-positive index of more than 1.5 at baseline. Proportions of patients positive for anti-JCV antibodies were similarly distributed between treatment groups throughout the study.
 

Similar immunogenicity

There was strong concordance regarding positivity for treatment-emergent antidrug antibodies between the biosim-NTZ and ref-NTZ groups (79.4% and 74.0%). This was also the case for antinatalizumab-neutralizing antibodies (69.0% and 66.2%).

“There was nothing that indicated immunogenicity is different” between the two agents, said Dr. Hemmer.

While this might change “when you look at longer time periods,” antibodies to natalizumab usually develop “very early on,” he added.

Dr. Hemmer noted that this comparison of the proposed biosimilar with the reference drug had no real surprises.

“If the immunogenicity is the same, the mode of action is the same, and the dose is the same, you would expect to have a similar clinical effect and also a similar side-effect profile, which is indeed the case,” he said.

Dr. Hemmer added that he has no insight as to when the drug might be approved but believes developers expect that to occur sometime this year.
 

Welcome results

Commenting on the study results, Torge Rempe, MD, assistant professor in the department of neurology, University of Florida, Gainesville, and the William T. And Janice M. Neely professor for research in MS, said he welcomes these new results showing the biosimilar matched the reference medication.

“The authors report no significant difference in their primary endpoint of cumulative number of active lesions as well as their secondary clinical endpoints of annualized relapse rate and changes from baseline Expanded Disability Status Scale scores,” said Dr. Rempe, who was not involved with the research.

The study also showed the reported adverse events were similar between the biosimilar and reference natalizumab, he noted.

However, although no cases of PML were uncovered during the study period, further research is needed to determine long-term safety in this area, Dr. Rempe said.

Finally, he agreed that the development of biosimilars such as this one addresses the issue of high annual costs for DMTs, an area of concern in the field of MS.

The study was funded by Polpharma Biologics. Dr. Hemmer has reported receiving personal fees from Polpharma and Sandoz during the conduct of the study and personal fees from Novartis, Biocom, and TG Therapeutics outside the submitted work. He has also received a patent for genetic determinants of antibodies against interferon-beta and a patent for KIR4.1 antibodies in MS; served on scientific advisory boards for Novartis; served as a data monitoring and safety committee member for AllergyCare, Polpharma Biologics, Sandoz, and TG Therapeutics; and received speaker honoraria from Desitin, grants from Regeneron for MS research, and funding from the Multiple MS EU consortium, the CLINSPECT-M consortium, and the German Research Foundation. Dr. Rempe has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An agent biologically similar to the humanized monoclonal antibody natalizumab is as effective and safe as the original reference drug for relapsing remitting multiple sclerosis (RRMS) – and has a similar level of immunogenicity, new research shows.

The investigators noted that these phase 3 trial findings are the final stage in the regulatory approval process.

“There will be a biosimilar that with respect to all parameters – efficacy, side effects, immunogenicity – doesn’t differ from the original drug and will probably be an option to consider to reduce treatment costs in MS,” said lead investigator Bernhard Hemmer, MD, a professor in the department of neurology, Technical University of Munich (Germany).

The findings were published online in JAMA Neurology.
 

Potential cost savings

Disease-modifying therapies (DMTs), particularly targeted biologics, have revolutionized the treatment of MS, including RRMS. Natalizumab, which was the first targeted biologic therapy approved for RRMS, is very effective and widely used, Dr. Hemmer said.

However, this and other DMTs are costly. Biosimilars, which are medicines clinically similar to an already marketed reference biologic medicine, can address this issue. In the areas of rheumatology and oncology, biosimilars have already demonstrated significant cost savings and improved treatment access.

The biosimilar natalizumab (biosim-NTZ), developed by Polpharma Biologics, is the first biosimilar monoclonal antibody therapy to be developed for MS.

Health authorities such as the Food and Drug Administration require comparative phase 3 studies to confirm there are no clinically relevant differences between a proposed biosimilar and its reference medicine.

The new multicenter, phase 3, double-blind, randomized trial – known as Antelope – included 264 adult patients with RRMS at 48 centers in seven Eastern European countries. Most study participants were women (61.4%), and their mean age was 36.7 years.

All study participants were randomly assigned to receive intravenous infusions every 4 weeks of 300 mg of biosim-NTZ or reference natalizumab (ref-NTZ) for a total of 12 infusions.

At week 24, 30 patients were switched from ref-NTZ to biosim-NTZ for the remainder of their infusions. Including such a population is required by regulatory agencies to ensure switching patients from a drug they’ve been taking to a new biosimilar does not introduce any concerns, said Dr. Hemmer.
 

Comparable efficacy, safety profile

The primary efficacy endpoint was the cumulative number of new active brain lesions on MRI.

At baseline, 48.1% of the biosimilar group and 45.9% of the reference drug group had at least one gadolinium-enhancing lesion. In addition, 96.9% of the biosimilar group had more than 15 T2 lesions, compared with 96.2% of the reference group.

At week 24, the mean difference between biosim-NTZ and ref-NTZ in the cumulative number of new active lesions was 0.17 (least square means, 0.34 vs. 0.45), with a 95% confidence interval of –0.61 to 0.94 and a point estimate within the prespecified margins of ± 2.1.

The annualized relapse rate for biosim-NTZ and ref-NTZ was similar at 24 weeks (0.21 vs. 0.15), as well as at 48 weeks (0.17 vs. 0.13). For Expanded Disability Status Scale scores, which were similar between treatment groups at baseline (mean, 3.4 vs. 3.2), change at 24 and 48 weeks was minimal and similar in both groups.

The safety profile was as expected for patients with RRMS receiving natalizumab. There were few adverse events of special interest, with similar proportions across all treatment groups.

The overall adverse-event profile for patients who switched from ref-NTZ to biosim-NTZ was similar to patients continuing ref-NTZ treatment and did not indicate any new or increased risks associated with switching.

Rates of treatment-emergent adverse events (TEAEs) were similar, at 64.9% for biosim-NTZ, 68.9% for ref-NTZ, and 73.3% for the switch group. The most-reported TEAEs among all treatment groups were nervous system disorders and infections and infestations.

Progressive multifocal leukoencephalopathy (PML), a rare and potentially fatal demyelinating disease of the central nervous system, is associated with some DMTs – notably ref-NTZ. It is caused by infection with the John Cunningham virus (JCV) (also referred to as human polyomavirus), the researchers noted.

As per the study protocol, no participant had a JCV-positive index of more than 1.5 at baseline. Proportions of patients positive for anti-JCV antibodies were similarly distributed between treatment groups throughout the study.
 

Similar immunogenicity

There was strong concordance regarding positivity for treatment-emergent antidrug antibodies between the biosim-NTZ and ref-NTZ groups (79.4% and 74.0%). This was also the case for antinatalizumab-neutralizing antibodies (69.0% and 66.2%).

“There was nothing that indicated immunogenicity is different” between the two agents, said Dr. Hemmer.

While this might change “when you look at longer time periods,” antibodies to natalizumab usually develop “very early on,” he added.

Dr. Hemmer noted that this comparison of the proposed biosimilar with the reference drug had no real surprises.

“If the immunogenicity is the same, the mode of action is the same, and the dose is the same, you would expect to have a similar clinical effect and also a similar side-effect profile, which is indeed the case,” he said.

Dr. Hemmer added that he has no insight as to when the drug might be approved but believes developers expect that to occur sometime this year.
 

Welcome results

Commenting on the study results, Torge Rempe, MD, assistant professor in the department of neurology, University of Florida, Gainesville, and the William T. And Janice M. Neely professor for research in MS, said he welcomes these new results showing the biosimilar matched the reference medication.

“The authors report no significant difference in their primary endpoint of cumulative number of active lesions as well as their secondary clinical endpoints of annualized relapse rate and changes from baseline Expanded Disability Status Scale scores,” said Dr. Rempe, who was not involved with the research.

The study also showed the reported adverse events were similar between the biosimilar and reference natalizumab, he noted.

However, although no cases of PML were uncovered during the study period, further research is needed to determine long-term safety in this area, Dr. Rempe said.

Finally, he agreed that the development of biosimilars such as this one addresses the issue of high annual costs for DMTs, an area of concern in the field of MS.

The study was funded by Polpharma Biologics. Dr. Hemmer has reported receiving personal fees from Polpharma and Sandoz during the conduct of the study and personal fees from Novartis, Biocom, and TG Therapeutics outside the submitted work. He has also received a patent for genetic determinants of antibodies against interferon-beta and a patent for KIR4.1 antibodies in MS; served on scientific advisory boards for Novartis; served as a data monitoring and safety committee member for AllergyCare, Polpharma Biologics, Sandoz, and TG Therapeutics; and received speaker honoraria from Desitin, grants from Regeneron for MS research, and funding from the Multiple MS EU consortium, the CLINSPECT-M consortium, and the German Research Foundation. Dr. Rempe has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Too little sleep or poor sleep quality during the teen years can significantly increase the risk for multiple sclerosis (MS) during adulthood, new research suggests.

In a large case-control study, individuals who slept less than 7 hours a night on average during adolescence were 40% more likely to develop MS later on. The risk was even higher for those who rated their sleep quality as bad.

On the other hand, MS was significantly less common among individuals who slept longer as teens – indicating a possible protective benefit.

While sleep duration has been associated with mortality or disease risk for other conditions, sleep quality usually has little to no effect on risk, lead investigator Torbjörn Åkerstedt, PhD, sleep researcher and professor of psychology, department of neuroscience, Karolinska Institutet, Stockholm, told this news organization.

“I hadn’t really expected that, but those results were quite strong, even stronger than sleep duration,” Dr. Åkerstedt said.

“We don’t really know why this is happening in young age, but the most suitable explanation is that the brain in still developing quite a bit, and you’re interfering with it,” he added.

The findings were published online in the Journal of Neurology, Neurosurgery and Psychiatry.
 

Strong association

Other studies have tied sleep deprivation to increased risk for serious illness, but the link between sleep and MS risk isn’t as well studied.

Previous research by Dr. Åkerstedt showed that the risk for MS was higher among individuals who took part in shift work before the age of 20. However, the impact of sleep duration or quality among teens was unknown.

The current Swedish population-based case-control study included 2,075 patients with MS and 3,164 without the disorder. All participants were asked to recall how many hours on average they slept per night between the ages of 15 and 19 years and to rate their sleep quality during that time.

Results showed that individuals who slept fewer than 7 hours a night during their teen years were 40% more likely to have MS as adults (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.7).

Poor sleep quality increased MS risk even more (OR, 1.5; 95% CI, 1.3-1.9).

The association remained strong even after adjustment for additional sleep on weekends and breaks and excluding shift workers.
 

Long sleep ‘apparently good’

The researchers also conducted several sensitivity studies to rule out confounders that might bias the association, such as excluding participants who reported currently experiencing less sleep or poor sleep.

“You would expect that people who are suffering from sleep problems today would be the people who reported sleep problems during their youth,” but that didn’t happen, Dr. Åkerstedt noted.

The investigators also entered data on sleep duration and sleep quality at the same time, thinking the data would cancel each other out. However, the association remained the same.

“Quite often you see that sleep duration would eliminate the effect of sleep complaints in the prediction of disease, but here both remain significant when they are entered at the same time,” Dr. Åkerstedt said. “You get the feeling that this might mean they act together to produce results,” he added.

“One other thing that surprised me is that long sleep was apparently good,” said Dr. Åkerstedt.

The investigators have conducted several studies on sleep duration and mortality. In recent research, they found that both short sleep and long sleep predicted mortality – “and often, long sleep is a stronger predictor than short sleep,” he said.
 

Underestimated problem?

Commenting on the findings, Kathleen Zackowski, PhD, associate vice president of research for the National Multiple Sclerosis Society in Baltimore, noted that participants were asked to rate their own sleep quality during adolescence, a subjective report that may mean sleep quality has an even larger association with MS risk.

“That they found a result with sleep quality says to me that there probably is a bigger problem, because I don’t know if people over- or underestimate their sleep quality,” said Dr. Zackowski, who was not involved with the research.

“If we could get to that sleep quality question a little more objectively, I bet that we’d find there’s a lot more to the story,” she said.

That’s a story the researchers would like to explore, Dr. Åkerstedt reported. Designing a prospective study that more closely tracks sleeping habits during adolescence and follows individuals through adulthood could provide valuable information about how sleep quality and duration affect immune system development and MS risk, he said.

Dr. Zackowski said clinicians know that MS is not caused just by a genetic abnormality and that other environmental lifestyle factors seem to play a part.

“If we find out that sleep is one of those lifestyle factors, this is very changeable,” she added.

The study was funded by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Brain Foundation, AFA Insurance, the European Aviation Safety Authority, the Tercentenary Fund of the Bank of Sweden, the Margaretha af Ugglas Foundation, the Swedish Foundation for MS Research, and NEURO Sweden. Dr. Åkerstadt has been supported by Tercentenary Fund of Bank of Sweden, AFA Insurance, and the European Aviation Safety Authority. Dr. Zackowski reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Too little sleep or poor sleep quality during the teen years can significantly increase the risk for multiple sclerosis (MS) during adulthood, new research suggests.

In a large case-control study, individuals who slept less than 7 hours a night on average during adolescence were 40% more likely to develop MS later on. The risk was even higher for those who rated their sleep quality as bad.

On the other hand, MS was significantly less common among individuals who slept longer as teens – indicating a possible protective benefit.

While sleep duration has been associated with mortality or disease risk for other conditions, sleep quality usually has little to no effect on risk, lead investigator Torbjörn Åkerstedt, PhD, sleep researcher and professor of psychology, department of neuroscience, Karolinska Institutet, Stockholm, told this news organization.

“I hadn’t really expected that, but those results were quite strong, even stronger than sleep duration,” Dr. Åkerstedt said.

“We don’t really know why this is happening in young age, but the most suitable explanation is that the brain in still developing quite a bit, and you’re interfering with it,” he added.

The findings were published online in the Journal of Neurology, Neurosurgery and Psychiatry.
 

Strong association

Other studies have tied sleep deprivation to increased risk for serious illness, but the link between sleep and MS risk isn’t as well studied.

Previous research by Dr. Åkerstedt showed that the risk for MS was higher among individuals who took part in shift work before the age of 20. However, the impact of sleep duration or quality among teens was unknown.

The current Swedish population-based case-control study included 2,075 patients with MS and 3,164 without the disorder. All participants were asked to recall how many hours on average they slept per night between the ages of 15 and 19 years and to rate their sleep quality during that time.

Results showed that individuals who slept fewer than 7 hours a night during their teen years were 40% more likely to have MS as adults (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.7).

Poor sleep quality increased MS risk even more (OR, 1.5; 95% CI, 1.3-1.9).

The association remained strong even after adjustment for additional sleep on weekends and breaks and excluding shift workers.
 

Long sleep ‘apparently good’

The researchers also conducted several sensitivity studies to rule out confounders that might bias the association, such as excluding participants who reported currently experiencing less sleep or poor sleep.

“You would expect that people who are suffering from sleep problems today would be the people who reported sleep problems during their youth,” but that didn’t happen, Dr. Åkerstedt noted.

The investigators also entered data on sleep duration and sleep quality at the same time, thinking the data would cancel each other out. However, the association remained the same.

“Quite often you see that sleep duration would eliminate the effect of sleep complaints in the prediction of disease, but here both remain significant when they are entered at the same time,” Dr. Åkerstedt said. “You get the feeling that this might mean they act together to produce results,” he added.

“One other thing that surprised me is that long sleep was apparently good,” said Dr. Åkerstedt.

The investigators have conducted several studies on sleep duration and mortality. In recent research, they found that both short sleep and long sleep predicted mortality – “and often, long sleep is a stronger predictor than short sleep,” he said.
 

Underestimated problem?

Commenting on the findings, Kathleen Zackowski, PhD, associate vice president of research for the National Multiple Sclerosis Society in Baltimore, noted that participants were asked to rate their own sleep quality during adolescence, a subjective report that may mean sleep quality has an even larger association with MS risk.

“That they found a result with sleep quality says to me that there probably is a bigger problem, because I don’t know if people over- or underestimate their sleep quality,” said Dr. Zackowski, who was not involved with the research.

“If we could get to that sleep quality question a little more objectively, I bet that we’d find there’s a lot more to the story,” she said.

That’s a story the researchers would like to explore, Dr. Åkerstedt reported. Designing a prospective study that more closely tracks sleeping habits during adolescence and follows individuals through adulthood could provide valuable information about how sleep quality and duration affect immune system development and MS risk, he said.

Dr. Zackowski said clinicians know that MS is not caused just by a genetic abnormality and that other environmental lifestyle factors seem to play a part.

“If we find out that sleep is one of those lifestyle factors, this is very changeable,” she added.

The study was funded by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Brain Foundation, AFA Insurance, the European Aviation Safety Authority, the Tercentenary Fund of the Bank of Sweden, the Margaretha af Ugglas Foundation, the Swedish Foundation for MS Research, and NEURO Sweden. Dr. Åkerstadt has been supported by Tercentenary Fund of Bank of Sweden, AFA Insurance, and the European Aviation Safety Authority. Dr. Zackowski reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Too little sleep or poor sleep quality during the teen years can significantly increase the risk for multiple sclerosis (MS) during adulthood, new research suggests.

In a large case-control study, individuals who slept less than 7 hours a night on average during adolescence were 40% more likely to develop MS later on. The risk was even higher for those who rated their sleep quality as bad.

On the other hand, MS was significantly less common among individuals who slept longer as teens – indicating a possible protective benefit.

While sleep duration has been associated with mortality or disease risk for other conditions, sleep quality usually has little to no effect on risk, lead investigator Torbjörn Åkerstedt, PhD, sleep researcher and professor of psychology, department of neuroscience, Karolinska Institutet, Stockholm, told this news organization.

“I hadn’t really expected that, but those results were quite strong, even stronger than sleep duration,” Dr. Åkerstedt said.

“We don’t really know why this is happening in young age, but the most suitable explanation is that the brain in still developing quite a bit, and you’re interfering with it,” he added.

The findings were published online in the Journal of Neurology, Neurosurgery and Psychiatry.
 

Strong association

Other studies have tied sleep deprivation to increased risk for serious illness, but the link between sleep and MS risk isn’t as well studied.

Previous research by Dr. Åkerstedt showed that the risk for MS was higher among individuals who took part in shift work before the age of 20. However, the impact of sleep duration or quality among teens was unknown.

The current Swedish population-based case-control study included 2,075 patients with MS and 3,164 without the disorder. All participants were asked to recall how many hours on average they slept per night between the ages of 15 and 19 years and to rate their sleep quality during that time.

Results showed that individuals who slept fewer than 7 hours a night during their teen years were 40% more likely to have MS as adults (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.7).

Poor sleep quality increased MS risk even more (OR, 1.5; 95% CI, 1.3-1.9).

The association remained strong even after adjustment for additional sleep on weekends and breaks and excluding shift workers.
 

Long sleep ‘apparently good’

The researchers also conducted several sensitivity studies to rule out confounders that might bias the association, such as excluding participants who reported currently experiencing less sleep or poor sleep.

“You would expect that people who are suffering from sleep problems today would be the people who reported sleep problems during their youth,” but that didn’t happen, Dr. Åkerstedt noted.

The investigators also entered data on sleep duration and sleep quality at the same time, thinking the data would cancel each other out. However, the association remained the same.

“Quite often you see that sleep duration would eliminate the effect of sleep complaints in the prediction of disease, but here both remain significant when they are entered at the same time,” Dr. Åkerstedt said. “You get the feeling that this might mean they act together to produce results,” he added.

“One other thing that surprised me is that long sleep was apparently good,” said Dr. Åkerstedt.

The investigators have conducted several studies on sleep duration and mortality. In recent research, they found that both short sleep and long sleep predicted mortality – “and often, long sleep is a stronger predictor than short sleep,” he said.
 

Underestimated problem?

Commenting on the findings, Kathleen Zackowski, PhD, associate vice president of research for the National Multiple Sclerosis Society in Baltimore, noted that participants were asked to rate their own sleep quality during adolescence, a subjective report that may mean sleep quality has an even larger association with MS risk.

“That they found a result with sleep quality says to me that there probably is a bigger problem, because I don’t know if people over- or underestimate their sleep quality,” said Dr. Zackowski, who was not involved with the research.

“If we could get to that sleep quality question a little more objectively, I bet that we’d find there’s a lot more to the story,” she said.

That’s a story the researchers would like to explore, Dr. Åkerstedt reported. Designing a prospective study that more closely tracks sleeping habits during adolescence and follows individuals through adulthood could provide valuable information about how sleep quality and duration affect immune system development and MS risk, he said.

Dr. Zackowski said clinicians know that MS is not caused just by a genetic abnormality and that other environmental lifestyle factors seem to play a part.

“If we find out that sleep is one of those lifestyle factors, this is very changeable,” she added.

The study was funded by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Brain Foundation, AFA Insurance, the European Aviation Safety Authority, the Tercentenary Fund of the Bank of Sweden, the Margaretha af Ugglas Foundation, the Swedish Foundation for MS Research, and NEURO Sweden. Dr. Åkerstadt has been supported by Tercentenary Fund of Bank of Sweden, AFA Insurance, and the European Aviation Safety Authority. Dr. Zackowski reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.